Browse result page of ThPDB2
This is the result page of the browse module of ThPDB2. This page gives the information about the query submitted by the user as per the browse category. Further details of the entries can be seen by clicking on the ID or THPP_ID. Further the user can sort the entries on the basis of various fields by clicking on the respective headers. The user can also download the results in various formats.
Tabular representation:
| ID | THPP_ID | Therapeutic Name | Sequence | Molecular Weight | Chemical Formula | Isoelectric Point | Hydrophobicity | Melting Point | Half Life | Description | Disease/Indication | Pharmacodynamics | Mechanism of Action | Toxicity | Metabolism | Absorption | Volume of Distribution | Clearance | Categories | Patent Number | Date of Issue | Date of Expiry | Drug Interaction | Target | Brand Name | Company | Brand Description | Prescribed for | Chemical Name | Formulation | Physical Appearance | Route of Administation | Recommended Dosage | Contraindication | Side Effects | Useful Links 1 | Useful Links 2 | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 10187 | Th1024 | Gramicidin D | >Th1024_Gramicidin_D VGALAVVVWLWLWLWX | 1811.253 | C96H135N19O16 | NA | NA | 229 | NA | Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids. The peptides assemble inside of the hydrophobic interior of the cellular lipid bilayer to form an alpha helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane. Gramicidin D is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic polysporin ophthalmic solution. | For treatment of skin lesions, surface wounds and eye infections | Gramicidin is particularly effective against gram-positive bacteria because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution | Gramicidin D binds and inserts itself into bacterial membranes (preference to gram-positive cell membranes) resulting in membrane disruption and permeabilization (it acts as a channel). This leads to loss of intracellular solutes (e.g., K+ and amino acids); dissipation of the transmembrane potential; inhibition of respiration; a reduction in ATP pools; and inhibition of DNA, RNA, and protein synthesis, which leads to cell death. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Anti-Infective Agents, Local, Membrane Proteins, P-glycoprotein inhibitors, P-glycoprotein substrates, Peptides, Peptides, Cyclic, Pore Forming Cytotoxic Proteins, Proteins, Throat Preparations | NA | NA | NA | NA | NA | Neosporin | Pfizer | Pfizer | Neosporin ointment is an antibiotic combination which works by killing sensitive bacteria on the skin or in wounds.Thus, treating and preventing infection due to minor cuts, scrapes, and burns. | NA | Each gram contains: neomycin sulfate equivalent to 3.5 mg neomycin base, polymyxin B sulfate equivalent to 10,000 polymyxin B units, bacitracin zinc equivalent to 400 bacitracin units, and white petrolatum, q.s. | Ointment | External use only | Apply the ointment every 3 or 4 hours for 7 to 10 days depending on the severity of the infection. | Individuals who have shown hypersensitivity to any of its components | Rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; skin irritation, pain, burning, cracking, redness, or peeling not present before using Neosporin ointment; worsening or recurrence of wound symptoms. | Link | NA | NA |
| 10188 | Th1024 | Gramicidin D | >Th1024_Gramicidin_D VGALAVVVWLWLWLWX | 1811.253 | C96H135N19O16 | NA | NA | 229 | NA | Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids. The peptides assemble inside of the hydrophobic interior of the cellular lipid bilayer to form an alpha helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane. Gramicidin D is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic polysporin ophthalmic solution. | For treatment of skin lesions, surface wounds and eye infections | Gramicidin is particularly effective against gram-positive bacteria because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution | Gramicidin D binds and inserts itself into bacterial membranes (preference to gram-positive cell membranes) resulting in membrane disruption and permeabilization (it acts as a channel). This leads to loss of intracellular solutes (e.g., K+ and amino acids); dissipation of the transmembrane potential; inhibition of respiration; a reduction in ATP pools; and inhibition of DNA, RNA, and protein synthesis, which leads to cell death. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Anti-Infective Agents, Local, Membrane Proteins, P-glycoprotein inhibitors, P-glycoprotein substrates, Peptides, Peptides, Cyclic, Pore Forming Cytotoxic Proteins, Proteins, Throat Preparations | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10189 | Th1024 | Gramicidin D | >Th1024_Gramicidin_D VGALAVVVWLWLWLWX | 1811.253 | C96H135N19O16 | NA | NA | 229 | NA | Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids. The peptides assemble inside of the hydrophobic interior of the cellular lipid bilayer to form an alpha helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane. Gramicidin D is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic polysporin ophthalmic solution. | For treatment of skin lesions, surface wounds and eye infections | Gramicidin is particularly effective against gram-positive bacteria because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution | Gramicidin D binds and inserts itself into bacterial membranes (preference to gram-positive cell membranes) resulting in membrane disruption and permeabilization (it acts as a channel). This leads to loss of intracellular solutes (e.g., K+ and amino acids); dissipation of the transmembrane potential; inhibition of respiration; a reduction in ATP pools; and inhibition of DNA, RNA, and protein synthesis, which leads to cell death. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Anti-Infective Agents, Local, Membrane Proteins, P-glycoprotein inhibitors, P-glycoprotein substrates, Peptides, Peptides, Cyclic, Pore Forming Cytotoxic Proteins, Proteins, Throat Preparations | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10190 | Th1024 | Gramicidin D | >Th1024_Gramicidin_D VGALAVVVWLWLWLWX | 1811.253 | C96H135N19O16 | NA | NA | 229 | NA | Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids. The peptides assemble inside of the hydrophobic interior of the cellular lipid bilayer to form an alpha helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane. Gramicidin D is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic polysporin ophthalmic solution. | For treatment of skin lesions, surface wounds and eye infections | Gramicidin is particularly effective against gram-positive bacteria because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution | Gramicidin D binds and inserts itself into bacterial membranes (preference to gram-positive cell membranes) resulting in membrane disruption and permeabilization (it acts as a channel). This leads to loss of intracellular solutes (e.g., K+ and amino acids); dissipation of the transmembrane potential; inhibition of respiration; a reduction in ATP pools; and inhibition of DNA, RNA, and protein synthesis, which leads to cell death. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Anti-Infective Agents, Local, Membrane Proteins, P-glycoprotein inhibitors, P-glycoprotein substrates, Peptides, Peptides, Cyclic, Pore Forming Cytotoxic Proteins, Proteins, Throat Preparations | NA | NA | NA | NA | NA | Sofradex | Sanofi | Sanofi | Used in the eye(s) to treat Inflammation in the eye when prevention of bacterial infection is also needed. Signs include sore, red or swollen eyes. It is used in the ear(s) to treat Inflammation of the ear canal (otitis externa) | NA | Each bottle contains 0.5% w/v of Framycetin Sulphate, Dexamethasone Sodium Metasulphobenzoate (equivalent to 0.050% w/v of Dexamethasone) and 0.005% w/v of Gramicidin. The other ingredients are citric acid, sodium citrate, lithium chloride, phenylethyl al | Sterile, clear, bright, colourless, aqueous solution | Auricular and Ocular use. | One or two drops applied to each affected eye up to six times daily or more frequently if required. Two or three drops instilled into the ear three or four times daily. | If glaucoma is present or herpetic keratitis (e.g. dendritic ulcer) is considered a possibility. Otitis Externa should not be treated when the eardrum is perforated because of the risk of ototoxicity. Hypersensitivity to framycetin sulphate, dexamethasone sodium metasulphobenzoate, gramicidin or to any of the excipients. | Stop using Sofradex if: You get any kind of skin problem, such as a rash or itching around your eyes or irritation burning, stinging, itching or swelling, your eyes have problems focussing or develop a blind spot. You may have increased pressure in the eye, you have difficulty seeing at night or notice that your eyesight is cloudy and fuzzy, or you see halos around lights. These could be signs of cataracts. This may occur after using the medicine for a long time | Link | NA | NA |
| 10191 | Th1024 | Gramicidin D | >Th1024_Gramicidin_D VGALAVVVWLWLWLWX | 1811.253 | C96H135N19O16 | NA | NA | 229 | NA | Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids. The peptides assemble inside of the hydrophobic interior of the cellular lipid bilayer to form an alpha helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane. Gramicidin D is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic polysporin ophthalmic solution. | For treatment of skin lesions, surface wounds and eye infections | Gramicidin is particularly effective against gram-positive bacteria because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution | Gramicidin D binds and inserts itself into bacterial membranes (preference to gram-positive cell membranes) resulting in membrane disruption and permeabilization (it acts as a channel). This leads to loss of intracellular solutes (e.g., K+ and amino acids); dissipation of the transmembrane potential; inhibition of respiration; a reduction in ATP pools; and inhibition of DNA, RNA, and protein synthesis, which leads to cell death. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Anti-Infective Agents, Local, Membrane Proteins, P-glycoprotein inhibitors, P-glycoprotein substrates, Peptides, Peptides, Cyclic, Pore Forming Cytotoxic Proteins, Proteins, Throat Preparations | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10192 | Th1024 | Gramicidin D | >Th1024_Gramicidin_D VGALAVVVWLWLWLWX | 1811.253 | C96H135N19O16 | NA | NA | 229 | NA | Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids. The peptides assemble inside of the hydrophobic interior of the cellular lipid bilayer to form an alpha helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane. Gramicidin D is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic polysporin ophthalmic solution. | For treatment of skin lesions, surface wounds and eye infections | Gramicidin is particularly effective against gram-positive bacteria because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution | Gramicidin D binds and inserts itself into bacterial membranes (preference to gram-positive cell membranes) resulting in membrane disruption and permeabilization (it acts as a channel). This leads to loss of intracellular solutes (e.g., K+ and amino acids); dissipation of the transmembrane potential; inhibition of respiration; a reduction in ATP pools; and inhibition of DNA, RNA, and protein synthesis, which leads to cell death. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Anti-Infective Agents, Local, Membrane Proteins, P-glycoprotein inhibitors, P-glycoprotein substrates, Peptides, Peptides, Cyclic, Pore Forming Cytotoxic Proteins, Proteins, Throat Preparations | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10229 | Th1031 | Interferon Alfa-2a, Recombinant | >Th1031_Interferon_Alfa-2a,_Recombinant CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | IM half-life of interferon alfa-2a is 6 hours to 8 hours | Its a type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a bbetter target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2-5 oligoadenylate synthetase (2-5 A synthetase) and protein kinase R. | It binds directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic a | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | 0.223 to 0.748 L/kg [healthy people] | 2.14 - 3.62 mL/min/kg [healthy] | Adjuvants, Immunologic, Alfa Interferons, Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Antiviral Agents, Biological Factors, Cancer immunotherapy, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Cytokines, Immunosuppressive Agents, Immunotherapy, Intercellular Signaling Peptides and Proteins, Interferon alpha, Interferon Type I, Interferon-alpha, Interferons, Myelosuppressive Agents, Peptides, Proteins | CA2172664 | 3-Oct-2000 | 26-Mar-2016 | Interferon increases the effect and toxicity of theophylline | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon A | Hoffmann-La Roche Inc | Hoffmann-La Roche Inc | To treat chronic hepatitis C and hairy cell leukemia in patients 18 years of age or older. In addition, it is indicated for chronic phase, Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) patients who are minimally pretreated (with | NA | 3 million IU (11.1 mcg/0.5 mL) Roferon-A (interferon alfa-2a, recombinant) per syringe  The solution is colorless and each 0.5 mL contains 3 MIU of Interferon alfa-2a, recombinant, 3.605 mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol as a | Solution | Subcutaneous Injection | Dosage for the treatment of chronic hepatitis C is 3 MIU three times a week (tiw) administered subcutaneously for 12 months (48-52 weeks). As an alternative, patients may be treated with an induction dose of 6 MIU tiw for the first 3 months (12 weeks) followed by 3 MIU tiw for 9 months (36 weeks). | Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components | Injection site reactions (pain/swelling/redness), headache, tiredness, diarrhea, upset stomach, loss of appetite, back pain, dizziness, dry mouth, taste changes, nausea, or vomiting may occur. Tooth and gum problems may sometimes occur during treatment. | Link | NA | NA |
| 10230 | Th1031 | Interferon Alfa-2a, Recombinant | >Th1031_Interferon_Alfa-2a,_Recombinant CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | Half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Its a type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a bbetter target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2-5 oligoadenylate synthetase (2-5 A synthetase) and protein kinase R. | It binds directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic a | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | 0.223 to 0.748 L/kg [healthy people] | 2.14 - 3.62 mL/min/kg [healthy] | Adjuvants, Immunologic, Alfa Interferons, Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Antiviral Agents, Biological Factors, Cancer immunotherapy, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Cytokines, Immunosuppressive Agents, Immunotherapy, Intercellular Signaling Peptides and Proteins, Interferon alpha, Interferon Type I, Interferon-alpha, Interferons, Myelosuppressive Agents, Peptides, Proteins | NA | NA | NA | Aminophylline interferon increases the effect and toxicity of theophylline | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Autoimmune hepatitis or hepatic decompensation (Child-Pugh class B and C) before or during treatment. | NA | Link | NA | NA |
| 10231 | Th1031 | Interferon Alfa-2a, Recombinant | >Th1031_Interferon_Alfa-2a,_Recombinant CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | NA | Its a type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a bbetter target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2-5 oligoadenylate synthetase (2-5 A synthetase) and protein kinase R. | It binds directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic a | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | 0.223 to 0.748 L/kg [healthy people] | 2.14 - 3.62 mL/min/kg [healthy] | Adjuvants, Immunologic, Alfa Interferons, Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Antiviral Agents, Biological Factors, Cancer immunotherapy, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Cytokines, Immunosuppressive Agents, Immunotherapy, Intercellular Signaling Peptides and Proteins, Interferon alpha, Interferon Type I, Interferon-alpha, Interferons, Myelosuppressive Agents, Peptides, Proteins | NA | NA | NA | Dyphylline interferon increases the effect and toxicity of theophylline | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | NA | Link | NA | NA |
| 10232 | Th1031 | Interferon Alfa-2a, Recombinant | >Th1031_Interferon_Alfa-2a,_Recombinant CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | NA | Its a type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a bbetter target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2-5 oligoadenylate synthetase (2-5 A synthetase) and protein kinase R. | It binds directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic a | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | 0.223 to 0.748 L/kg [healthy people] | 2.14 - 3.62 mL/min/kg [healthy] | Adjuvants, Immunologic, Alfa Interferons, Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Antiviral Agents, Biological Factors, Cancer immunotherapy, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Cytokines, Immunosuppressive Agents, Immunotherapy, Intercellular Signaling Peptides and Proteins, Interferon alpha, Interferon Type I, Interferon-alpha, Interferons, Myelosuppressive Agents, Peptides, Proteins | NA | NA | NA | Oxtriphylline, interferon increases the effect and toxicity of theophylline | NA | Veldona | Amarillo Biosciences | Amarillo Biosciences | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10233 | Th1031 | Interferon Alfa-2a, Recombinant | >Th1031_Interferon_Alfa-2a,_Recombinant CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | NA | Its a type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a bbetter target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2-5 oligoadenylate synthetase (2-5 A synthetase) and protein kinase R. | It binds directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic a | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | 0.223 to 0.748 L/kg [healthy people] | 2.14 - 3.62 mL/min/kg [healthy] | Adjuvants, Immunologic, Alfa Interferons, Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Antiviral Agents, Biological Factors, Cancer immunotherapy, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Cytokines, Immunosuppressive Agents, Immunotherapy, Intercellular Signaling Peptides and Proteins, Interferon alpha, Interferon Type I, Interferon-alpha, Interferons, Myelosuppressive Agents, Peptides, Proteins | NA | NA | NA | Roferon-A (interferon alfa-2a, recombinant) has been reported to reduce the clearance of theophylline. Synergistic toxicity has been observed when Roferon-A (interferon alfa-2a, recombinant) is administered in combination with zidovudine (AZT) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10409 | Th1067 | Daptomycin | NA | 1620.693 | C72H101N17O26 | NA | NA | NA | Normal range: 7.5-9 hours 27.83 ± 14.85 hours in patients with creatinine clearance <30 mL/min | Daptomycin is a lipopeptide antibiotic that kills susceptible gram positive bacteria by disrupting their membrane potential. It is a naturally-occurring compound found in the soil bacterium <i>Streptomyces roseosporus</i>. Antibiotics are used in the treatment of infections caused by bacteria. They work by killing bacteria or preventing their growth. Daptomycin will not work for colds, flu, or other virus infections. It was approved in September 2003 for the treatment of complicated skin and soft tissue infections. It has a safety profile similar to other agents commonly administered to treat gram-positive infections. | For the treatment of complicated skin and skin structure infections caused by susceptible strains of Gram-positive microorganisms. | Daptomycin is a 13 member amino acid cyclic lipopeptide antibiotic active against Gram-positive bacteria only. It has proven in vitro activity against enterococci (including glycopeptide-resistant Enterococci (GRE)), staphylococci (including methicillin-resistant <i>Staphylococcus aureus</i>), streptococci and corynebacteria. Daptomycin is derived from the fermentation product of Streptomyces roseosporus. | Daptomycin appears to bind or insert into the outer membrane of gram positive bacteria. The binding and integration of daptomycin into the cell membrane is calcium dependent. Calcium ions cause a conformational change in daptomycin, augmenting its amphipathicity (hydrophilic head group and hydrophobic tail group), leading to incorporation into the cell membrane. This binding causes rapid depolarisation, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death. The bactericidal activity of daptomycin is concentration-dependent. There is in vitro evidence of synergy with β-lactam antibiotics. | NA | Minor amounts of three oxidative metabolites and one unidentified compound have been detected in urine. The site of metabolism has not been identified. | NA | 0.1 L/Kg [healthy adult subjects] | As daptomycin is primarily renally excreted, patients with mild, moderate, and severe renal impairment had reduced total plasma clearance 9, 22, and 46 percent lower than healthy controls, respectively. Daptomycin clearance was also lower in obese (15-23%) and geriatric (aged 75 and older, by 35%) patients, whereas it tended to be higher in pediatric patients, even when normalized for body weight | Agents Causing Muscle Toxicity, Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Antibacterials for Systemic Use, Antiinfectives for Systemic Use, Cyclic Lipopeptides, Drugs that are Mainly Renally Excreted, Lipids, Lipopeptide Antibacterial, Lipopeptides, P-glycoprotein substrates, Peptides, Peptides, Cyclic | US6468967 | 22-Oct-2002 | 24-Sep-2019 | NA | Cytoplasmic membrane | CUBICIN | Cubist Pharmaceuticals, Inc | Cubist Pharmaceuticals, Inc | Complicated skin and skin structure infections (cSSSI), Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates | N-decanoyl-L-tryptophyl-Dasparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-Dseryl-threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanine ε1-lactone | CUBICIN contains 500 mg of daptomycin and reconstituted with 0.9% sodium chloride injection. The only inactive ingredient is sodium hydroxide, which is used in minimal quantities for pH adjustment. | CUBICIN is a Sterile, preservative-free, pale yellow to light brown, lyophilized cake containing approx 500 mg of daptomycin | Intravenous (Intravenous) Injection | CUBICIN 4 mg/kg should be administered intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days. Staphylococcus aureus Bloodstream Infections (Bacteremia) - CUBICIN 6 mg/kg should be administered intravenously in 0.9% sodium chloride injection once every 24 hours for 2 to 6 weeks. | CUBICIN is contraindicated in patients with known hypersensitivity to daptomycin | fatigue, weakness, rigors, flushing, hypersensitivity, leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, increased International Normalized Ratio (INR), supraventricular arrhythmia, eczema, abdominal distension, stomatitis, jaundice, increased serum lactate dehydrogenase, hypomagnesemia, increased serum bicarbonate, electrolyte disturbance, myalgia, muscle cramps, muscle weakness, arthralgia, vertigo, mental status change, paresthesia, taste disturbance, eye irritation | Link | NA | NA |
| 10410 | Th1067 | Daptomycin | NA | 1620.693 | C72H101N17O26 | NA | NA | NA | 0.51 ± 6.51 hours in hemodialysis patients | Daptomycin is a lipopeptide antibiotic that kills susceptible gram positive bacteria by disrupting their membrane potential. It is a naturally-occurring compound found in the soil bacterium <i>Streptomyces roseosporus</i>. Antibiotics are used in the treatment of infections caused by bacteria. They work by killing bacteria or preventing their growth. Daptomycin will not work for colds, flu, or other virus infections. It was approved in September 2003 for the treatment of complicated skin and soft tissue infections. It has a safety profile similar to other agents commonly administered to treat gram-positive infections. | For the treatment of complicated skin and skin structure infections caused by susceptible strains of Gram-positive microorganisms. | Daptomycin is a 13 member amino acid cyclic lipopeptide antibiotic active against Gram-positive bacteria only. It has proven in vitro activity against enterococci (including glycopeptide-resistant Enterococci (GRE)), staphylococci (including methicillin-resistant <i>Staphylococcus aureus</i>), streptococci and corynebacteria. Daptomycin is derived from the fermentation product of Streptomyces roseosporus. | Daptomycin appears to bind or insert into the outer membrane of gram positive bacteria. The binding and integration of daptomycin into the cell membrane is calcium dependent. Calcium ions cause a conformational change in daptomycin, augmenting its amphipathicity (hydrophilic head group and hydrophobic tail group), leading to incorporation into the cell membrane. This binding causes rapid depolarisation, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death. The bactericidal activity of daptomycin is concentration-dependent. There is in vitro evidence of synergy with β-lactam antibiotics. | NA | Minor amounts of three oxidative metabolites and one unidentified compound have been detected in urine. The site of metabolism has not been identified. | NA | 0.1 L/Kg [healthy adult subjects] | As daptomycin is primarily renally excreted, patients with mild, moderate, and severe renal impairment had reduced total plasma clearance 9, 22, and 46 percent lower than healthy controls, respectively. Daptomycin clearance was also lower in obese (15-23%) and geriatric (aged 75 and older, by 35%) patients, whereas it tended to be higher in pediatric patients, even when normalized for body weight | Agents Causing Muscle Toxicity, Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Antibacterials for Systemic Use, Antiinfectives for Systemic Use, Cyclic Lipopeptides, Drugs that are Mainly Renally Excreted, Lipids, Lipopeptide Antibacterial, Lipopeptides, P-glycoprotein substrates, Peptides, Peptides, Cyclic | USRE39071 | 18-Apr-2006 | 15-Jun-2016 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10411 | Th1067 | Daptomycin | NA | 1620.693 | C72H101N17O26 | NA | NA | NA | 27.56 ± 4.53 hours in continuous ambulatory peritoneal dialysis (CAPD) patients | Daptomycin is a lipopeptide antibiotic that kills susceptible gram positive bacteria by disrupting their membrane potential. It is a naturally-occurring compound found in the soil bacterium <i>Streptomyces roseosporus</i>. Antibiotics are used in the treatment of infections caused by bacteria. They work by killing bacteria or preventing their growth. Daptomycin will not work for colds, flu, or other virus infections. It was approved in September 2003 for the treatment of complicated skin and soft tissue infections. It has a safety profile similar to other agents commonly administered to treat gram-positive infections. | For the treatment of complicated skin and skin structure infections caused by susceptible strains of Gram-positive microorganisms. | Daptomycin is a 13 member amino acid cyclic lipopeptide antibiotic active against Gram-positive bacteria only. It has proven in vitro activity against enterococci (including glycopeptide-resistant Enterococci (GRE)), staphylococci (including methicillin-resistant <i>Staphylococcus aureus</i>), streptococci and corynebacteria. Daptomycin is derived from the fermentation product of Streptomyces roseosporus. | Daptomycin appears to bind or insert into the outer membrane of gram positive bacteria. The binding and integration of daptomycin into the cell membrane is calcium dependent. Calcium ions cause a conformational change in daptomycin, augmenting its amphipathicity (hydrophilic head group and hydrophobic tail group), leading to incorporation into the cell membrane. This binding causes rapid depolarisation, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death. The bactericidal activity of daptomycin is concentration-dependent. There is in vitro evidence of synergy with β-lactam antibiotics. | NA | Minor amounts of three oxidative metabolites and one unidentified compound have been detected in urine. The site of metabolism has not been identified. | NA | 0.1 L/Kg [healthy adult subjects] | As daptomycin is primarily renally excreted, patients with mild, moderate, and severe renal impairment had reduced total plasma clearance 9, 22, and 46 percent lower than healthy controls, respectively. Daptomycin clearance was also lower in obese (15-23%) and geriatric (aged 75 and older, by 35%) patients, whereas it tended to be higher in pediatric patients, even when normalized for body weight | Agents Causing Muscle Toxicity, Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Antibacterials for Systemic Use, Antiinfectives for Systemic Use, Cyclic Lipopeptides, Drugs that are Mainly Renally Excreted, Lipids, Lipopeptide Antibacterial, Lipopeptides, P-glycoprotein substrates, Peptides, Peptides, Cyclic | CA2344318 | 4-Jul-2006 | 24-Sep-2019 | NA | B-lymphocyte antigen CD20,Low affinity immunoglobulin gamma Fc region receptor III-B,Complement C1r subcomponent,Complement C1q subcomponent subunit A,Complement C1q subcomponent subunit B,Complement C1q subcomponent subunit C,Low affinity immunoglobulin gamma Fc region receptor III-A,Complement C1s subcomponent,High affinity immunoglobulin gamma Fc receptor I,Low affinity immunoglobulin gamma Fc region receptor II-a,Low affinity immunoglobulin gamma Fc region receptor II-b,Low affinity immunoglobulin gamma Fc region receptor II-c | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10455 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S9 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1341537 | 31-Jul-2007 | 31-Jul-2024 | Topotecan with Filgrastim may increase the adverse effects. Increased risk of prolonged neutropenia. Filgrastim should be administered at least 24 hours following Topotecan therapy. Monitor for signs and symptoms of neutropenia | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Accofil | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10456 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Biograstim | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10457 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Filgrastim Hexal | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10458 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Filgrastim Ratiopharm | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10459 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Granix | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10460 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Grastofil | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10461 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Neupogen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10462 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Nivestim | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10463 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Nivestym | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10464 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Nypozi | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10465 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Ratiograstim | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10466 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Tevagrastim | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10467 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Zarxio | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10468 | Th1082 | Filgrastim | >Th1082_Filgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S10 | 5.65 | 0.209 | 60 | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11 There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day | Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive | Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70% | Vd, healthy subjects and cancer patients = 150 mL/kg | Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration. | Amino Acids, Peptides, and Proteins,Antineoplastic and Immunomodulating Agents,Biological Factors,Colony-Stimulating Factors,Glycoconjugates,Glycoproteins,Granulocyte Colony-Stimulating Factors,Hematologic Agents,Hematopoietic Cell Growth Factors,Increased Myeloid Cell Production,Leukocyte Growth Factor,Peptides,Proteins | CA1339071 | 29-Jul-1997 | 29-Jul-2014 | NA | Granulocyte colony-stimulating factor receptor,Neutrophil elastase | Zarzio | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10564 | Th1115 | Teicoplanin | NA | 1879.658 | C88H97Cl2N9O33 | NA | NA | NA | 70-100 hrs | Glycopeptide antibiotic. It is a mixture of several compounds majorly teicoplanin A2-1 through A2-5, along with four minor ones, teicoplanin RS-1 through RS-4. They all share a same glycopeptide core, referred to as teicoplanin A3-1, which is a fused ring structure bound by two carbohydrates (mannose and N-acetylglucosamine). The components also contain a third carbohydrate moiety, β-D-glucosamine, and differ only by the length and conformation of a side chain attached to it. | For the treatment of bacterial infections caused by susceptible microorganisms. | Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. It is a glycopeptide antiobiotic extracted from Actinoplanes teichomyceticus, with a similar spectrum of activity to vancomycin. Its mechanism of action is to inhibit bacterial cell wall synthesis. Oral teicoplanin has been demonstrated to be effective in the treatment of pseudomembranous colitis and Clostridium difficile-associated diarrhoea, with comparable efficacy to vancomycin. | Teicoplanin inhibits peptidoglycan polymerization, resulting in inhibition of bacterial cell wall synthesis and cell death. | NA | NA | NA | NA | NA | Anti-Bacterial Agents | NA | NA | NA | NA | D-Ala-D-Ala moiety of NAM/NAG peptide subunits of peptidoglycan | Targocid | NPS Pharmaceuticals | NPS Pharmaceuticals | Acts against Gram-postive bacteria including methicillin-resistant Staphylococcus aureus and Enterococcus fecalis. Targocid is indicated in adults and in children from birth for the parenteral treatment of the following infections skin and soft tissue infections, bone and joint infections, hospital acquired pneumonia, community acquired pneumonia, complicated urinary tract infections, infective endocarditis, continuous ambulatory peritoneal dialysis (CAPD), bacteraemia that occurs in association with any of the indications listed above. Targocid is also indicated as an alternative oral treatment for Clostridium difficile infection-associated diarrhoea and colitis. | NA | Each vial of Targocid injection contains 400 mg teicoplanin. The glass vial also contains an inactive ingredient, sodium chloride which is included to minimise stinging and pain when the injection is administered. There are no dyes, gluten or preservatives in Targocid injection. | Light yellow solid | Intramuscular, Intravenous | NA | Serious, life-threatening hypersensitivity reactions, sometimes fatal, have been reported with teicoplanin (e.g. anaphylactic shock). If an allergic reaction to teicoplanin occurs, treatment should be discontinued immediately and appropriate emergency measures should be initiated. Teicoplanin must be administered with caution in patients with known hypersensitivity to vancomycin, as crossed hypersensitivity reactions, including fatal anaphylactic shock, may occur. However, a prior history of red man syndrome with vancomycin is not a contraindication to the use of teicoplanin. | Infusion related reactions, Severe bullous reactions, Nephrotoxicity, Ototoxicity, Superinfection | Link | NA | NA |
| 10780 | Th1181 | Filgrastim-sndz | >Th1181_Filgrastim-sndz MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S9 | 5.65 | NA | NA | Approximately 3.5 hours | NA | Patients with Cancer Receiving Myelosuppressive Chemotherapy: to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever. Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy: to reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML). Patients with Cancer Undergoing Bone Marrow Transplantation: to reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation. Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy: for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis. Patients with Severe Chronic Neutropenia: for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia. | In patients with patients with various nonmyeloid malignancies‚ administration of filgrastim resulted in a dose-dependent increase in circulating neutrophil counts over the dose range of 1 to 70 mcg/kg/day. This increase in neutrophil counts was observed whether filgrastim was administered intravenous (1 to70 mcg/kg twice daily)‚ subcutaneous (1 to 3 mcg/kg once daily)‚ or by continuous subcutaneous infusion (3 to 11 mcg/kg/day). With discontinuation of filgrastim therapy‚ neutrophil counts returned to baseline in most cases within 4 days. Isolated neutrophils displayed normal phagocytic (measured by zymosan-stimulated chemoluminescence) and chemotactic (measured by migration under agarose using N-formyl-methionyl-leucyl- phenylalanine [fMLP] as the chemotaxin) activity in vitro. | Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation. Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens). G-CSF is not species-specific and has been shown to have minimal direct in vivo or in vitro effects on the production or activity of hematopoietic cell types other than the neutrophil lineage. | NA | NA | NA | NA | NA | NA | NA | NA | NA | The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Bleomycin; The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Cyclophosphamide; The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Topotecan. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10781 | Th1181 | Filgrastim-sndz | >Th1181_Filgrastim-sndz MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S9 | 5.65 | NA | NA | Approximately 3.5 hours | NA | Patients with Cancer Receiving Myelosuppressive Chemotherapy: to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever. Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy: to reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML). Patients with Cancer Undergoing Bone Marrow Transplantation: to reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation. Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy: for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis. Patients with Severe Chronic Neutropenia: for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia. | In patients with patients with various nonmyeloid malignancies‚ administration of filgrastim resulted in a dose-dependent increase in circulating neutrophil counts over the dose range of 1 to 70 mcg/kg/day. This increase in neutrophil counts was observed whether filgrastim was administered intravenous (1 to70 mcg/kg twice daily)‚ subcutaneous (1 to 3 mcg/kg once daily)‚ or by continuous subcutaneous infusion (3 to 11 mcg/kg/day). With discontinuation of filgrastim therapy‚ neutrophil counts returned to baseline in most cases within 4 days. Isolated neutrophils displayed normal phagocytic (measured by zymosan-stimulated chemoluminescence) and chemotactic (measured by migration under agarose using N-formyl-methionyl-leucyl- phenylalanine [fMLP] as the chemotaxin) activity in vitro. | Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation. Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens). G-CSF is not species-specific and has been shown to have minimal direct in vivo or in vitro effects on the production or activity of hematopoietic cell types other than the neutrophil lineage. | NA | NA | NA | NA | NA | NA | NA | NA | NA | The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Bleomycin; The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Cyclophosphamide; The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Topotecan. | NA | Zarxio | Sandoz Inc | Sandoz Inc | NA | NA | 300 ug/.5mL Injection | solution | intravenous; subcutaneous | The recommended starting dosage of ZARXIO is 5 mcg/kg/day‚ administered as a single daily injection by subcutaneous injection‚ by short intravenous infusion (15 to 30 minutes)‚ or by continuous intravenous infusion. Obtain a complete blood count (CBC) and platelet count before instituting ZARXIO therapy and monitor twice weekly during therapy. Consider dose escalation in increments of 5 mcg/kg for each chemotherapy cycle‚ according to the duration and severity of the absolute neutrophil count (ANC) nadir. Recommend stopping ZARXIO if the ANC increases beyond 10‚000/mm³ | ZARXIO is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim or pegfilgrastim products | Splenic Rupture; Acute Respiratory Distress Syndrome; Serious Allergic Reactions ; Sickle Cell Disorders; Glomerulonephritis; Alveolar Hemorrhage and Hemoptysis; Capillary Leak Syndrome; Thrombocytopenia; Leukocytosis; Cutaneous Vasculitis. | Link | NA | NA |
| 10782 | Th1181 | Filgrastim-sndz | >Th1181_Filgrastim-sndz MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP | 18800 | C845H1339N223O243S9 | 5.65 | NA | NA | Approximately 3.5 hours | NA | Patients with Cancer Receiving Myelosuppressive Chemotherapy: to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever. Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy: to reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML). Patients with Cancer Undergoing Bone Marrow Transplantation: to reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation. Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy: for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis. Patients with Severe Chronic Neutropenia: for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia. | In patients with patients with various nonmyeloid malignancies‚ administration of filgrastim resulted in a dose-dependent increase in circulating neutrophil counts over the dose range of 1 to 70 mcg/kg/day. This increase in neutrophil counts was observed whether filgrastim was administered intravenous (1 to70 mcg/kg twice daily)‚ subcutaneous (1 to 3 mcg/kg once daily)‚ or by continuous subcutaneous infusion (3 to 11 mcg/kg/day). With discontinuation of filgrastim therapy‚ neutrophil counts returned to baseline in most cases within 4 days. Isolated neutrophils displayed normal phagocytic (measured by zymosan-stimulated chemoluminescence) and chemotactic (measured by migration under agarose using N-formyl-methionyl-leucyl- phenylalanine [fMLP] as the chemotaxin) activity in vitro. | Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation. Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens). G-CSF is not species-specific and has been shown to have minimal direct in vivo or in vitro effects on the production or activity of hematopoietic cell types other than the neutrophil lineage. | NA | NA | NA | NA | NA | NA | NA | NA | NA | The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Bleomycin; The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Cyclophosphamide; The risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Topotecan. | NA | Zarxio | Sandoz Inc | Sandoz Inc | NA | NA | 480 ug/.8mL Injection | solution | intravenous; subcutaneous | The recommended starting dosage of ZARXIO is 5 mcg/kg/day‚ administered as a single daily injection by subcutaneous injection‚ by short intravenous infusion (15 to 30 minutes)‚ or by continuous intravenous infusion. Obtain a complete blood count (CBC) and platelet count before instituting ZARXIO therapy and monitor twice weekly during therapy. Consider dose escalation in increments of 5 mcg/kg for each chemotherapy cycle‚ according to the duration and severity of the absolute neutrophil count (ANC) nadir. Recommend stopping ZARXIO if the ANC increases beyond 10‚000/mm³ | ZARXIO is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim or pegfilgrastim products | Splenic Rupture; Acute Respiratory Distress Syndrome; Serious Allergic Reactions ; Sickle Cell Disorders; Glomerulonephritis; Alveolar Hemorrhage and Hemoptysis; Capillary Leak Syndrome; Thrombocytopenia; Leukocytosis; Cutaneous Vasculitis. | Link | NA | NA |
| 10828 | Th1194 | Tuberculin Purified Protein Derivative | NA | NA | NA | NA | NA | NA | NA | Aplisol (tuberculin PPD, diluted) is a sterile aqueous solution of a purified protein fraction for intradermal administration as an aid in the diagnosis of tuberculosis. The solution is stabilized with polysorbate (Tween) 80, buffered with potassium and sodium phosphates and contains 0.25% phenol as a preservative. The purified protein fraction is isolated from culture media filtrates of a human strain of Mycobacterium tuberculosis. | Used in the detection of infection with Mycobacterium tuberculosis. | NA | NA | Some adverse effects at the injection site include pain, discomfort, pyrexia, and erythema, rash, hemorrhage, hematoma and rarely ulcer and necrosis. Other unwanted effects include severe hypersensitivity reactions, dyspnea, generalized rash and syncope. | NA | NA | NA | NA | Antigens,Antigens, Bacterial,Antihistamine Drugs,Biological Factors,Cell-mediated Immunity,Compounds used in a research, industrial, or household setting,Indicators and Reagents,Laboratory Chemicals,Skin Test Antigen,Tuberculin,Tuberculosis,Tuberculosis Skin Test | NA | NA | NA | NA | Toll-like receptor 2 | Aplisol | Par Pharmaceutical, Inc. | Par Pharmaceutical, Inc. | Detecting tuberculosis (TB) infection. | NA | The solution is stabilized with polysorbate (Tween) 80, buffered with potassium and sodium phosphates and contains approximately 0.35% phenol as a preservative. | solution for injection | intradermal | Diagnosis: Mantoux test, inject 0.1 mL (5 tuberculin units) intradermally; the result is read 48 to 72 hours after administration | Previous positive tuberculin skin test responsiveness suppressed within 6 weeks of viral infection, inactive TB, immunosuppression, geriatric | Commonside effect include Pain, itching, or redness at the injection site. Sever side effect mmay occur Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blisters; open sores. | Link | NA | NA |
| 10842 | Th1205 | Obiltoxaximab | NA | 148000 | NA | NA | NA | NA | NA | Obiltoxaximab, an affinity-enhanced monoclonal antibody (Mab), is used for prevention and treatment of infection and death caused by anthrax toxin. Obiltoxaximab is a chimeric IgG1 kappa monoclonal antibody (mAb) that binds the PA component of B. anthracis toxin. It has an approximate molecular weight of 148 kDa. | Investigated for use/treatment in anthrax exposure, bacterial infection, crohn's disease, and graft versus host disease. | NA | ETI-204 is an affinity-enhanced, de-immunized antibody, which means that its ability to bind to its target pathogen has been strengthened and that elements that might cause an immune response have been removed. ETI-204 targets and binds to Protective Antigen, which prevents the anthrax toxins from binding to and entering the cells in the body, thereby preventing death. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins,Anthrax Protective Antigen-directed Antibody,Anthrax Protective Antigen-directed Antibody Interactions,Antibodies,Antiinfectives for Systemic Use,Biological Products,Blood,Blood Proteins,Body Fluids,Complex Mixtures,Fluids and Secretions,Globulins,Hemic and Immune Systems,Immune Sera,Immune Sera and Immunoglobulins,Immunoglobulins,Immunoproteins,Proteins,Serum,Serum Globulins,Specific Immunoglobulins | NA | NA | NA | NA | NA | Anthim | Elusys Therapeutics, Inc. | Elusys Therapeutics, Inc. | ANTHIM is indicated in adult and pediatric patients for the treatment of inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs.; Also is indicated for prophylaxis of inhalational anthrax due to B. anthracis when alternative therapies are not available or not appropriate. | NA | Solution | Liquid | Intravenous infusion | The recommended dosage of ANTHIM in adult patients is a single dose of 16 mg/kg administered intravenously over 90 minutes (1 hour and 30 minutes); For adult patients weighing less than 40 kg. | NA | Hypersensitivity and Anaphylaxis | Link | NA | NA |
| 10868 | Th1229 | Hepatitis A Vaccine | NA | NA | NA | NA | NA | NA | Evaluation of pharmacokinetic properties is not required for vaccines. | Two types of HAV vaccines are currently available internationally: 1. Formaldehyde-inactivated vaccines: Inactivated HAV vaccines are used in most countries. Monovalent inactivated HAV vaccines are available in paediatric dose (0.5 ml) for children aged 1 year to 15 years, and in adult dose (1 ml). 2. Live attenuated vaccines (based on H2 or LA-1 HAV strains): These vaccines are manufactured and used mainly in China and India. Inactivated hepatitis A vaccines are safe and highly effective. Traditionally, a two-dose schedule is recommended, particularly in travellers at substantial risk of contracting hepatitis A and in immunocompromised individuals. However, in healthy individuals, comparable effectiveness has been achieved with a single dose. The Chinese live attenuated hepatitis A vaccines have been shown to be safe and highly protective (95%) against clinical infection for at least 3 years. Among the adverse effects from Hepatitis A vaccine injection are fatigue, fever > 99.5°F (37.5°C), induration, redness, and swelling of the injection site and malaise. Anorexia and nausea could be possible side effects. | Hepatitis A vaccine is indicated for active immunization against disease caused by hepatitis A virus (HAV). It is approved for use in persons 12 months of age and older. Primary immunization should be administered at least 2 weeks prior to expected exposure to HAV. HAVRIX® will not prevent hepatitis infection caused by other agents such as hepatitis B virus, hepatitis C virus, hepatitis E virus or other pathogens known to infect the liver. In areas of low to intermediate prevalence of hepatitis A, immunization with HAVRIX® is particularly recommended in subjects who are, or will be, at increased risk of infection such as: * Travelers: Persons traveling to areas where the prevalence of hepatitis A is high. These areas include Africa, Asia, the Mediterranean basin, the Middle East, Central and South America. * Armed Forces: Armed Forces personnel who travel to higher endemicity areas or to areas where hygiene is poor have an increased risk of HAV infection. Active immunization is indicated for these individuals. * Persons for whom Hepatitis A is an Occupational Hazard: These include employees in day-care centres, nursing, medical and paramedical personnel in hospitals and institutions, especially gastroenterology and pediatric units, sewage workers, and food handlers, among others. * Persons for whom there is an Increased Risk of Transmission of Hepatitis A: e.g. homosexuals, persons with multiple sexual partners, abusers of injectable drugs, hemophiliac patients. * Contacts of Infected Persons: Since virus shedding of infected persons may occur for a prolonged period, active immunization of close contacts is recommended. * Specific Population Groups known to have Higher Incidence of Hepatitis A: e.g. North American Indians, Inuits, recognized community-wide HAV epidemics. * Subjects with chronic liver disease or who are at risk of developing chronic liver disease e.g. Hepatitis B (HB) and Hepatitis C (HC) chronic carriers and alcohol abusers. | Elevation of Anti-Hepatitis A antibodies which gives protection against Hepatitis A infection. | The hepatitis A virus belongs to the picornavirus family. It is one of several hepatitis viruses that cause systemic disease with pathology in the liver. The incubation period for hepatitis A averages 28 days (range: 15 to 50 days). The course of hepatitis A infection is extremely variable, ranging from asymptomatic infection to icteric hepatitis and death. The presence of antibodies to HAV confers protection against hepatitis A infection. However, the lowest titer needed to confer protection has not been determined. | LD50 information for the hepatitis A vaccine is not readily available in the literature. The prescribing information for the inactivated Hepatitis A vaccine indicates that postmarketing reports of adverse effects following an overdose with the vaccine that were similar to those that are normally expected. This may include pain or redness at the injection site, headache, irritability, appetite loss, and other symptoms. Prescribing information also advises contacting the local poison control center in the case of an overdose.[L338] | NA | NA | NA | NA | Actively Acquired Immunity,Inactivated Hepatitis A Virus Vaccine,Vaccines | NA | NA | NA | NA | B-lymphocytes | Avaxim | Sanofi Pasteur Limited | Sanofi Pasteur Limited | AVAXIM is indicated for active immunisation against infection caused by hepatitis A virus in susceptible adults and adolescents of 16 years of age and above. | NA | Each 0.5 mL dose of sterile, whitish, cloudy suspension, contains 80 antigen units of inactivated hepatitis A virus. Nonmedicinal ingredients: aluminum hydroxide (expressed as aluminum): 0.15 mg; 2-phenoxyethanol: 2.5 µL; formaldehyde: 12.5 µg; polysorbate 80 in less than 750 µg; medium 199, water for injection up to: 0.5 mL; neomycin: trace amounts. | Suspension | Intramuscular | NA | Hypersensitivity to the active substance(s) or to any of the excipients. | diarrhea, drowsiness, fatigue, fever, generally feeling unwell, headache, irritability, loss of appetite, muscle or joint achiness, nausea or vomiting, pain and redness at the injection site, swelling or hard lump at the injection site, weakness might occur as side reaction | Link | NA | NA |
| 10869 | Th1229 | Hepatitis A Vaccine | NA | NA | NA | NA | NA | NA | Evaluation of pharmacokinetic properties is not required for vaccines. | Two types of HAV vaccines are currently available internationally: 1. Formaldehyde-inactivated vaccines: Inactivated HAV vaccines are used in most countries. Monovalent inactivated HAV vaccines are available in paediatric dose (0.5 ml) for children aged 1 year to 15 years, and in adult dose (1 ml). 2. Live attenuated vaccines (based on H2 or LA-1 HAV strains): These vaccines are manufactured and used mainly in China and India. Inactivated hepatitis A vaccines are safe and highly effective. Traditionally, a two-dose schedule is recommended, particularly in travellers at substantial risk of contracting hepatitis A and in immunocompromised individuals. However, in healthy individuals, comparable effectiveness has been achieved with a single dose. The Chinese live attenuated hepatitis A vaccines have been shown to be safe and highly protective (95%) against clinical infection for at least 3 years. Among the adverse effects from Hepatitis A vaccine injection are fatigue, fever > 99.5°F (37.5°C), induration, redness, and swelling of the injection site and malaise. Anorexia and nausea could be possible side effects. | Hepatitis A vaccine is indicated for active immunization against disease caused by hepatitis A virus (HAV). It is approved for use in persons 12 months of age and older. Primary immunization should be administered at least 2 weeks prior to expected exposure to HAV. HAVRIX® will not prevent hepatitis infection caused by other agents such as hepatitis B virus, hepatitis C virus, hepatitis E virus or other pathogens known to infect the liver. In areas of low to intermediate prevalence of hepatitis A, immunization with HAVRIX® is particularly recommended in subjects who are, or will be, at increased risk of infection such as: * Travelers: Persons traveling to areas where the prevalence of hepatitis A is high. These areas include Africa, Asia, the Mediterranean basin, the Middle East, Central and South America. * Armed Forces: Armed Forces personnel who travel to higher endemicity areas or to areas where hygiene is poor have an increased risk of HAV infection. Active immunization is indicated for these individuals. * Persons for whom Hepatitis A is an Occupational Hazard: These include employees in day-care centres, nursing, medical and paramedical personnel in hospitals and institutions, especially gastroenterology and pediatric units, sewage workers, and food handlers, among others. * Persons for whom there is an Increased Risk of Transmission of Hepatitis A: e.g. homosexuals, persons with multiple sexual partners, abusers of injectable drugs, hemophiliac patients. * Contacts of Infected Persons: Since virus shedding of infected persons may occur for a prolonged period, active immunization of close contacts is recommended. * Specific Population Groups known to have Higher Incidence of Hepatitis A: e.g. North American Indians, Inuits, recognized community-wide HAV epidemics. * Subjects with chronic liver disease or who are at risk of developing chronic liver disease e.g. Hepatitis B (HB) and Hepatitis C (HC) chronic carriers and alcohol abusers. | Elevation of Anti-Hepatitis A antibodies which gives protection against Hepatitis A infection. | The hepatitis A virus belongs to the picornavirus family. It is one of several hepatitis viruses that cause systemic disease with pathology in the liver. The incubation period for hepatitis A averages 28 days (range: 15 to 50 days). The course of hepatitis A infection is extremely variable, ranging from asymptomatic infection to icteric hepatitis and death. The presence of antibodies to HAV confers protection against hepatitis A infection. However, the lowest titer needed to confer protection has not been determined. | LD50 information for the hepatitis A vaccine is not readily available in the literature. The prescribing information for the inactivated Hepatitis A vaccine indicates that postmarketing reports of adverse effects following an overdose with the vaccine that were similar to those that are normally expected. This may include pain or redness at the injection site, headache, irritability, appetite loss, and other symptoms. Prescribing information also advises contacting the local poison control center in the case of an overdose.[L338] | NA | NA | NA | NA | Actively Acquired Immunity,Inactivated Hepatitis A Virus Vaccine,Vaccines | NA | NA | NA | NA | B-lymphocytes | Havrix | Dispensing Solutions, Inc. | Dispensing Solutions, Inc. | HAVRIX® is indicated for active immunization against disease caused by hepatitis A virus (HAV) | NA | Each 1-mL adult dose of vaccine contains 1440 EL.U. of viral antigen, adsorbed on 0.5 mg of aluminum as aluminum hydroxide. It contains few excipients: Amino acid supplement (0.3% w/v) in a phosphate-buffered saline solution and polysorbate 20 (0.05 mg/mL). | Suspension | Intramuscular | Primary immunization for children and adolescents (12 months through 18 years of age) consists of a single 0.5-mL dose and a 0.5-mL booster dose administered anytime between 6 and 12 months later. | Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis A containing vaccine, or to any component of HAVRIX, including neomycin, is a contraindication to administration of HAVRIX | Injection site hematoma, upper respiratory tract infections, Insomnia etc | Link | NA | NA |
| 10870 | Th1230 | Human Varicella-Zoster Immune Globulin | NA | NA | NA | NA | NA | NA | Human Varicella-Zoster Immunoglobulin has a half-life of about 18-24 days following intravenous administration and 24-30 days following intramuscular administration. | Human Varicella-Zoster Immune Globulin is a solvent/detergent-treated sterile liquid preparation of purified human immune globulin G (IgG) containing antibodies to varicella zoster virus (anti-VZV). | Indicated for reducing the severity of chicken pox (varicella zoster virus) infections in high risk individuals after exposure | Provides passive immunization for nonimmune individuals exposed to varicella zoster virus, thereby reducing the severity of varicella infections | NA | Since the drug was prepared from human plasma pool, it may contain other infectious agents such as viruses and Creutzfeldt-Jakob disease (vCJD) agent. Hypersensitivity reactions such as allergic or anaphylactic reactions may occur. More common adverse effects include pain at injection site, headache, and rash. Rare adverse effects from immune globulin intravenous therapy include thrombotic events, renal dysfunction and acute renal failure, and noncardiogenic pulmonary edema. An LD50 was not determined, as the maximal dose used did not kill any experimental animals. | Immune globulins are metabolized in the reticuloendothelial system. | Intravenous administration of varicella zoster antibodies tends to persist for 6 weeks or longer. Following intramuscular administration of varicella immune globulin products, varicella antibodies are detectable within 2-3 days. The peak levels of varicella antibodies is expected to occur within 3-7 days of VariZIG administration. | Following intravenous administration of varicella zoster VZIG, anti-varicella zoster antibodies are expected to be quickly distributed between plasma and extravascular spaces with complete and immediate bioavailability. Intramuscular administration achieves nearly 100% bioavailability. | NA | Antibody | NA | NA | NA | The passive transfer of antibodies with immune globulin administration may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella | varicella zoster virus | VARIZIG | NA | NA | It is indicated for post-exposure prophylaxis of varicella in high risk individuals. | NA | It is available in a single-use vial of 125 IU. Each 125 IU vial of VARIZIG contains less than 156 milligrams of total protein, mostly human immune globulin G (IgG). VARIZIG contains no preservative | lyophilized powder for solution | Intramuscular | Depending on patient size, divide the IM dose and administer in 2 or more injection sites; not to exceed 3 mL/injection site | Hypersensitivity to human immunoglobulins | The most common adverse drug reactions (reported by ≥ 1% of subjects) observed in clinical trials for all subjects and patients (n=601) are the following:injection site pain (3%),headache (2%),rash (including terms pruritus, rash, rash erythematous, rash vesicular and urticaria) (1%),fatigue (1%),chills (1%),nausea (1%) | Link | NA | NA |
| 10872 | Th1232 | Lenograstim | NA | 18668 | C840-H1330-N222-O242-S8 | NA | NA | NA | The pharmacokinetic profile of lenograstim is similar in healthy volunteers and cancer patients with elimination half-life (t½β) values of 2.3 - 3.3 hrs (volunteers); 2.8-7.5 hrs (cancer patients) following sc administration, and 0.8 - 2.1 hrs (volunteers); 1.1 - 4.0 hrs (cancer patients) following iv administration. | Lenograstim is a recombinant granulocyte colony-stimulating factor which functions as an immunostimulator. | The drug is used to reduce the risk of life-threatening infection in patients with neutropenia, particularly after cytotoxic chemotherapy. GRANOCYTE ( Lenograstim) is indicated as a treatment to reduce the duration of neutropenia and the severity of infections in patients with non-myeloid malignancy who have undergone autologous or allogeneic bone marrow transplantation, or treatment with established cytotoxic chemotherapy and in addition to reduce the incidence of infection associated with established cytotoxic chemotherapy. GRANOCYTE is also indicated to mobilise peripheral blood progenitor cells (PBPCs) with GRANOCYTE alone, or after myelosuppressive chemotherapy, in order to accelerate haematopoietic recovery by infusion of such cells, after myelosuppressive or myeloablative therapy. GRANOCYTE is also indicated to accelerate the engraftment of these cells after their reinfusion. GRANOCYTE is also indicated for the treatment of severe chronic neutropenia including congenital agranulocytosis (Kostmann's syndrome). | Lenograstim has been confirmed as a valuable adjunct to minimise the haematological toxicity of myelosuppressive chemotherapy in patients with malignant disease. The drug also enhances neutrophil recovery in patients undergoing stem cell rescue, and assists PBSC mobilisation. | Lenograstim is the glycosylated recombinant form of human granulocyte colony stimulating factor. Lenograstim accelerates neutrophil recovery significantly after chemotherapy, with beneficial effects on clinical end-points such as incidence of laboratory-confirmed infection and length of hospital stay. Chemotherapy dose intensity has also been increased in patients receiving lenograstim, notably those with breast or small cell lung cancer, although improvements in tumour response and survival have not been demonstrated. Lenograstim also assists neutrophil recovery in patients undergoing bone marrow transplantation, and stimulates the production of peripheral blood stem cells (PBSCs) for autologous transfusion after aggressive chemotherapy. | Species observed : Human (Man) Test type: TDLo ( Lowest Published Toxic Dose) Route of exposure: Subcutaneous Dose/Duration: 21428mg/kg/15 Toxic Effect: Skin and appendages: Dermatitis, allergic ( after systemic exposure ) Species observed : Rodent - Rat Test type: LD50 Route of exposure: Oral Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value Species observed : Rodent - Rat Test type: LD50 Route of exposure: Subcutaneous Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value Species observed : Rodent - Rat Test type: LD50 Route of exposure: Intravenous Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value Species observed : Mammal - Dog Test type: LD50 Route of exposure: Intravenous Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value Species observed : Mammal - Dog Test type: LD50 Route of exposure: Subcutaneous Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value | Lenograstim is metabolised to peptides. | During repeated dosing (iv and sc routes), peak serum concentrations (at the end of iv infusion or after sc injection) are proportional to the injected dose. Repeated dosing with lenograstim by the two injection routes results in no evidence of drug accumulation. | Apparent distribution volume (Vd area) is approximately 52 ± 5 mL/kg body weight. | Plasma clearance of lenograstim increased 3-fold (from 50 up to 150 mL/min) during repeated sc dosing. | Antineoplastic and Immunomodulating Agents | NA | NA | NA | NA | Granulocyte colony-stimulating factor receptor | Granocyte | NA | NA | Reducing the duration of neutropenia and risk of infection in people treated with chemotherapy for cancer. | L-treonine-colony-stimulating factor | NA | Solid | Subcutaneous or Intravenous | NA | People with malignancies affecting myeloid cell | Decrease in the number of platelets in the blood (thrombocytopenia), Headache, Feeling weak, Bone pain, Back pain, Elevated levels of liver enzymes | Link | NA | NA |
| 10881 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Amino Acids, Peptides, and Proteins | 1339047 | 27-05-1997 | 27-05-2014 | Cyclophosphamide,Nandrolone phenpropionate,Nandrolone decanoate,Nandrolone,Ramipril,Fosinopril,Trandolapril,Benazepril,Enalapril,Moexipril,Lisinopril,Perindopril,Quinapril,Omapatrilat,Rescinnamine,Captopril,Cilazapril,Spirapril,Temocapril,Enalaprilat,Imidapril,Zofenopril,Delapril,Benazeprilat,Fosinoprilat,Ramiprilat,Trandolaprilat,Moexiprilat,Perindoprilat,Quinaprilat,Quinoline Yellow WS,Cilazaprilat,Vindesine,Vinorelbine,Vincristine,Vinblastine,Vintafolide,Vinflunine,Vincamine,Lenalidomide,Thalidomide,Pomalidomide,Cetuximab,Denileukin diftitox,Leuprolide,Peginterferon alfa-2a,Goserelin,Asparaginase Escherichia coli,Aldesleukin,Gemtuzumab ozogamicin,Pegaspargase,Trastuzumab,Rituximab,Tositumomab,Alemtuzumab,Octreotide,Interferon alfa-2b,Bevacizumab,Masoprocol,Bortezomib,Pipobroman,Cladribine,Cabergoline,Anagrelide,Carmustine,Chlorotrianisene,Amsacrine,Pamidronic acid,Bleomycin,Chlorambucil,Raltitrexed,Mitomycin,Bexarotene,Valproic acid,Gefitinib,Floxuridine,Megestrol acetate,Tioguanine,Aminoglutethimide,Valrubicin,Sorafenib,Streptozocin,Trifluridine,Gemcitabine,Teniposide,Epirubicin,Altretamine,Flutamide,Cisplatin,Alitretinoin,Oxaliplatin,Erlotinib,Toremifene,Fluorouracil,Pentostatin,Methotrexate,Medroxyprogesterone acetate,Imatinib,Clofarabine,Prednisone,Pemetrexed,Mitotane,Nilutamide,Tamoxifen,Daunorubicin,Porfimer sodium,Tretinoin,Irinotecan,Etoposide,Uracil mustard,Dacarbazine,Temozolomide,Aminolevulinic acid,Prednisolone,Mechlorethamine,Testolactone,Azacitidine,Fulvestrant,Carboplatin,Methylprednisolone,Dactinomycin,Cytarabine,Exemestane,Doxorubicin,Hydroxyurea,Letrozole,Busulfan,Topotecan,Mercaptopurine,Melphalan,Fludarabine,Capecitabine,Trilostane,Bicalutamide,Trimetrexate,Procarbazine,Arsenic trioxide,Idarubicin,Ifosfamide,Estramustine,Mitoxantrone,Lomustine,Anastrozole,Paclitaxel,Dexamethasone,Docetaxel,Dasatinib,Lapatinib,Decitabine,Sunitinib,Panitumumab,Nelarabine,Everolimus,Genistein,8-azaguanine,Epothilone D,7-Hydroxystaurosporine,Hadacidin,2-Methoxyestradiol,Geldanamycin,Vorinostat,Fumagillin,Patupilone,Tubercidin,Sparfosic acid,Alvocidib,2-(4-Chlorophenyl)-5-Quinoxalinecarboxamide,Brequinar,Piritrexim,Rhodamine 6G,Batimastat,3,4-Dihydroxybenzoic Acid,Fotemustine,Sparsomycin,Tretazicar,Seocalcitol,Monastrol,Nebularine,Afimoxifene,Thiotepa,Fleroxacin,Metoprine,Camptothecin,Suramin,Urethane,Cyproterone acetate,Ixabepilone,Cediranib,Tirapazamine,Omacetaxine mepesuccinate,Halofuginone,Nilotinib,Vapreotide,Thymalfasin,Galiximab,Sitimagene ceradenovec,Ranpirnase,Pirfenidone,Epratuzumab,Tipifarnib,Troxacitabine,Oregovomab,Banoxantrone,Plitidepsin,Satraplatin,Belinostat,Amonafide,Fenretinide,Tetrathiomolybdate,Labetuzumab,Trabectedin,Elsamitrucin,Bavituximab,Pracinostat,Cobimetinib,Gallium nitrate,Ecabet,Vandetanib,Rindopepimut,Canertinib,Motexafin gadolinium,7-ethyl-10-hydroxycamptothecin,Pelitinib,Alanosine,Ramucirumab,Farletuzumab,Veltuzumab,Palifosfamide,Trabedersen,Trastuzumab emtansine,Oglufanide,Irofulven,Abiraterone,Inotuzumab ozogamicin,KOS-1584,CT-011,Transcrocetinate,Glembatumumab vedotin,Aldoxorubicin,AV-412,Filanesib,Olaratumab,Rubitecan,Garenoxacin,Plevitrexed,Paclitaxel trevatide,Romidepsin,IMO-2055,Ipilimumab,Nimotuzumab,Pixantrone,Seliciclib,Atrasentan,Ridaforolimus,Vadimezan,Exisulind,Amrubicin,Lonidamine,Maxacalcitol,Temsirolimus,Elotuzumab,Tucidinostat,Sapacitabine,Pertuzumab,Indisulam,Annamycin,Endostatin,Tezacitabine,Semaxanib,Diethylnorspermine,Squalamine,Porfiromycin,MLN576,Pazopanib,Midostaurin,Panobinostat,Catumaxomab,Bosutinib,Axitinib,Volociximab,Ofatumumab,Degarelix,Methyltestosterone,Buserelin,Ginsenoside C,Bendamustine,Cabazitaxel,Hydroxyprogesterone caproate,Lanreotide,Plicamycin,Pralatrexate,Triptorelin,Veliparib,Hexestrol,Nocodazole,Puromycin,Efaproxiral,TNP-470,Vismodegib,Crizotinib,Brentuximab vedotin,Eribulin,Cabozantinib,Ruxolitinib,Vemurafenib,Asparaginase Erwinia chrysanthemi,Carfilzomib,Regorafenib,Enzalutamide,Ponatinib,Formestane,Trametinib,Dabrafenib,Radium Ra 223 dichloride,Afatinib,Obinutuzumab,Flumequine,Carmofur,Miltefosine,Nivolumab,Siltuximab,Pembrolizumab,Blinatumomab,Ibrutinib,Idelalisib,Ceritinib,Palbociclib,Olaparib,Dinutuximab,Lenvatinib,Nintedanib,Dienogest,Sonidegib,Niguldipine,Tegafur,Artesunate,Silibinin,Osimertinib,Daratumumab,Necitumumab,Ixazomib,Alectinib,Roquinimex,Masitinib,Venetoclax,Atezolizumab,Pirarubicin,Aclarubicin,Zorubicin,Temoporfin,Conatumumab,Dactolisib,Rabusertib,Ortataxel,Treosulfan,2-chloroethyl-3-sarcosinamide-1-nitrosourea,Ilorasertib,Durvalumab,Misonidazole,Epacadostat,Encorafenib,Endostar,Ribociclib,Icotinib,Bryostatin 1,Talazoparib,Tremelimumab,Niraparib,GSK-2636771,Tivozanib,Saracatinib,Talaporfin,Neratinib,Mocetinostat,Crenolanib,Entinostat,Acridine Carboxamide,Infigratinib,CUDC-907,Efatutazone,Apalutamide,Rociletinib,Guadecitabine,6-O-benzylguanine,Avelumab,Carboxyamidotriazole,Dacomitinib,Binimetinib,Rilotumumab,Tesevatinib,Glasdegib,Entrectinib,Vosaroxin,Abemaciclib,Alpelisib,Triptolide,Broxuridine,Naquotinib,Trebananib,Anecortave,Vesnarinone,Mafosfamide,LCL-161,Lorvotuzumab mertansine,Taselisib,Namitecan,Lorlatinib,Gilteritinib,Duligotuzumab,Rigosertib,Erdafitinib,Cordycepin,CUDC-101,Binetrakin,Exatecan,Zalutumumab,Lurtotecan,KRN-7000,Platinum,CG-200745,Epofolate,Brigatinib,OBP-801,Rucaparib,Navitoclax,Bizelesin,Ricolinostat,Indirubin,Merestinib,R-306465,10-hydroxycamptothecin,Sagopilone,Sulforaphane,Belotecan,Taurolidine,Copanlisib,Mogamulizumab,9-aminocamptothecin,Molgramostim,Oltipraz,Pyrazoloacridine,Abexinostat,Fosbretabulin,Dacetuzumab,Apaziquone,Combretastatin,Mizoribine,Onapristone,PU-H71,Givinostat,Beloranib,Soblidotin,Salirasib,Moxetumomab pasudotox,Gusperimus,Phenethyl Isothiocyanate,Methylselenocysteine,Intetumumab,Dolastatin 10,Etanidazole,Lometrexol,Ecromeximab,Prednimustine,Buthionine sulfoximine,Dianhydrogalactitol,Indole-3-carbinol,Fiacitabine,Trofosfamide,Nolatrexed,Mitolactol,Pinometostat,Doxifluridine,Didox,Mitoguazone,Pexidartinib,Penclomedine,Deoxyspergualin,Acteoside,Rebastinib,Hypericin,Tocladesine,Liarozole,Nimustine,X-396,Sizofiran,Nedaplatin,Olmutinib,Daidzein,Tiazofurine,Triaziquone,Demecolcine,Mannosulfan,Etoglucid,Edrecolomab,Lentinan,Mitobronitol,Oxolinic acid,Semustine,Carboquone,Vorozole,Paclitaxel poliglumex,Oblimersen,Ranimustine,Enasidenib,Iniparib,Talimogene laherparepvec,Coumermycin A1,Toyocamycin,Tretamine,Tetrandrine,Dofequidar,Dexniguldipine,Ivosidenib,Methylprednisolone hemisuccinate,Prednisone acetate,Combretastatin A4,Cemiplimab,Larotrectinib,Tagraxofusp,Rivoceranib,AZD-5991,ONC-201,Ensartinib,Human interleukin-2,Lintuzumab,Bermekimab,Etirinotecan pegol,Zanubrutinib,NUC-1031,Voruciclib,KRN-5500,Perillyl alcohol,Tefinostat,Biochanin A,Dihematoporphyrin ether,SOR-C13,Pidilizumab,Nanatinostat,Tallimustine,Volasertib,Isatuximab,Pemigatinib,Capmatinib,Selpercatinib,Brexucabtagene autoleucel,Pralsetinib,Selinexor,Fedratinib,Polatuzumab vedotin,Axicabtagene ciloleucel,Tucatinib,Darolutamide,Tepotinib,Lisocabtagene maraleucel,Umbralisib,Idecabtagene vicleucel,Dostarlimab,5'-S-methyl-5'-thioadenosine,Trichostatin A,Talactoferrin alfa,Quizartinib,Ripretinib,Edodekin alfa,Droloxifene,Abagovomab,Magrolimab,Nazartinib,Pegylated Recombinant Human Arginase I,Inbakicept,Tisagenlecleucel,Trastuzumab deruxtecan,Belzutifan,Curcumin,Tisotumab vedotin | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 1000 IU/0.5ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10882 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Antianemic Preparations | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 2000 IU/1.0ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10883 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Biological Factors | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 3000 IU/0.3ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10884 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Blood and Blood Forming Organs | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 4000 IU/0.4ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10885 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Carbohydrates | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 5000 IU/0.5ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10886 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Colony-Stimulating Factors | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 6000 IU/0.6ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10887 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Cytokines | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 8000 IU/0.8ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10888 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Erythropoiesis-Stimulating Agents | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 10000 IU/1.0ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10889 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Erythropoietin, genetics | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 7000 IU/0.7ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10890 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Glycoconjugates | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 9000 IU/0.9ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10891 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Glycoproteins | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 20000 IU/0.5ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10892 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Hematinics | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 30000 IU/0.75ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10893 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Hematologic Agents | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 40000 IU/1.0ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10894 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Hematopoietic Cell Growth Factors | NA | NA | NA | NA | Erythropoietin receptor | Abseamed | Medice Arzneimittel Pütter Gmb H Co. Kg | Medice Arzneimittel Pütter Gmb H Co. Kg | Intravenous; Subcutaneous | 40000 IU/1ml | NA | The most common side effects with Abseamed (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Abseamed contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Abseamed is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Abseamed is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic kidney failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Abseamed is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10895 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Increased Erythroid Cell Production | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 1000 IU/0.5ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10896 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Intercellular Signaling Peptides and Proteins | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 2000 IU/1.0ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10897 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Peptides | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 3000 IU/0.3ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10898 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | Proteins | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 4000 IU/0.4ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10899 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 5000 IU/0.5ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10900 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 6000 IU/0.6ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10901 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 8000 IU/0.8ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10902 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 10000 IU/1.0ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10903 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 7000 IU/0.7ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10904 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 9000 IU/0.9ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10905 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 20000 IU/0.5ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10906 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 30000 IU/0.75ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10907 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 40000 IU/1ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10908 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Binocrit | Sandoz | Sandoz | Intravenous; Subcutaneous | 10000 IU/1ml | NA | The most common side effects with Binocrit (which may affect more than 1 in 10 people) are nausea (feeling sick),diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Binocrit contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Binocrit is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Binocrit is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Binocrit is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10909 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Biopoin | Teva | Teva | Intravenous; Subcutaneous | 1000 IU/0.5ml | NA | The most common side effects with Biopoin (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Biopoin, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Biopoin works in the body in the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Biopoin is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10910 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Biopoin | Teva | Teva | Intravenous; Subcutaneous | 2000 IU/0.5ml | NA | The most common side effects with Biopoin (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Biopoin, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Biopoin works in the body in the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Biopoin is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10911 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Biopoin | Teva | Teva | Intravenous; Subcutaneous | 3000 IU/0.5ml | NA | The most common side effects with Biopoin (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Biopoin, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Biopoin works in the body in the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Biopoin is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10912 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Biopoin | Teva | Teva | Intravenous; Subcutaneous | 4000 IU/0.5ml | NA | The most common side effects with Biopoin (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Biopoin, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Biopoin works in the body in the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Biopoin is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10913 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Biopoin | Teva | Teva | Intravenous; Subcutaneous | 5000 IU/0.5ml | NA | The most common side effects with Biopoin (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Biopoin, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Biopoin works in the body in the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Biopoin is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10914 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Biopoin | Teva | Teva | Intravenous; Subcutaneous | 10000 IU/1.0ml | NA | The most common side effects with Biopoin (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Biopoin, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Biopoin works in the body in the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Biopoin is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10915 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Biopoin | Teva | Teva | Intravenous; Subcutaneous | 20000 IU/1.0ml | NA | The most common side effects with Biopoin (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Biopoin, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Biopoin works in the body in the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Biopoin is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10916 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Biopoin | Teva | Teva | Intravenous; Subcutaneous | 30000 IU/1.0ml | NA | The most common side effects with Biopoin (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Biopoin, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Biopoin works in the body in the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Biopoin is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10917 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 1000 IU/0.5ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10918 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 2000 IU/1.0ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10919 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 3000 IU/0.3ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10920 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 4000 IU/0.4ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10921 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 5000 IU/0.5ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10922 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 6000 IU/0.6ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10923 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 8000 IU/0.8ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10924 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 10000 IU/1.0ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10925 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 7000 IU/0.7ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10926 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 9000 IU/0.9ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10927 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 20000 IU/0.5ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10928 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 30000 IU/0.75ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10929 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 40000 IU/1.0ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10930 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epoetin Alfa Hexal | Hexal Ag | Hexal Ag | Intravenous; Subcutaneous | 40000 IU/1ml | NA | The most common side effects with Epoetin Alfa Hexal (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, vomiting, fever and headache. Flu-like illness may occur especially at the start of treatment. | Epoetin Alfa Hexal contains the active substance epoetin alfa and is a ‘biosimilar medicine’. This means that Epoetin Alfa Hexal is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Epoetin Alfa Hexal is Eprex/Erypo. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with ‘chronic kidney failure’ (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy for certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that can be taken in adult patients with moderate anaemia and normal blood iron levels who are going to have an operation and donate their own blood before surgery (autologous blood transfusion); to reduce the need for blood transfusions in adults with moderate anaemia who are about to undergo major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Epoetin Alfa Hexal is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10931 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epogen | Amgen | Amgen | Intravenous; Subcutaneous | 40000 1/1mL | Epogen is contraindicated in patients with: Uncontrolled hypertension [see WARNINGS AND PRECAUTIONS] Pure red cell aplasia (PRCA) that begins after treatment with Epogen or other erythropoietin protein drugs [see WARNINGS AND PRECAUTIONS] Serious allergic reactions to Epogen [see WARNINGS AND PRECAUTIONS] Epogen from multiple-dose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and lactating women [see WARNINGS AND PRECAUTIONS, Use In Specific Populations]. | headache, body aches, diarrhea, cold symptoms (stuffy nose, sneezing, sore throat, cough), joint pain, bone pain, muscle pain or spasms, dizziness, depression, weight loss, sleep problems (insomnia), nausea, vomiting, trouble swallowing, or injection site reactions (pain, tenderness, or irritation). | Epogen is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Epogen is used to treat anemia caused by chemotherapy... | Epogen is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10932 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epogen | AMGEN INC | AMGEN INC | Intravenous; Subcutaneous | 2000 [iU]/1mL | Epogen is contraindicated in patients with: Uncontrolled hypertension [see WARNINGS AND PRECAUTIONS] Pure red cell aplasia (PRCA) that begins after treatment with Epogen or other erythropoietin protein drugs [see WARNINGS AND PRECAUTIONS] Serious allergic reactions to Epogen [see WARNINGS AND PRECAUTIONS] Epogen from multiple-dose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and lactating women [see WARNINGS AND PRECAUTIONS, Use In Specific Populations]. | headache, body aches, diarrhea, cold symptoms (stuffy nose, sneezing, sore throat, cough), joint pain, bone pain, muscle pain or spasms, dizziness, depression, weight loss, sleep problems (insomnia), nausea, vomiting, trouble swallowing, or injection site reactions (pain, tenderness, or irritation). | Epogen is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Epogen is used to treat anemia caused by chemotherapy... | Epogen is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10933 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epogen | AMGEN INC | AMGEN INC | Intravenous; Subcutaneous | 3000 [iU]/1mL | Epogen is contraindicated in patients with: Uncontrolled hypertension [see WARNINGS AND PRECAUTIONS] Pure red cell aplasia (PRCA) that begins after treatment with Epogen or other erythropoietin protein drugs [see WARNINGS AND PRECAUTIONS] Serious allergic reactions to Epogen [see WARNINGS AND PRECAUTIONS] Epogen from multiple-dose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and lactating women [see WARNINGS AND PRECAUTIONS, Use In Specific Populations]. | headache, body aches, diarrhea, cold symptoms (stuffy nose, sneezing, sore throat, cough), joint pain, bone pain, muscle pain or spasms, dizziness, depression, weight loss, sleep problems (insomnia), nausea, vomiting, trouble swallowing, or injection site reactions (pain, tenderness, or irritation). | Epogen is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Epogen is used to treat anemia caused by chemotherapy... | Epogen is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10934 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epogen | AMGEN INC | AMGEN INC | Intravenous; Subcutaneous | 4000 [iU]/1mL | Epogen is contraindicated in patients with: Uncontrolled hypertension [see WARNINGS AND PRECAUTIONS] Pure red cell aplasia (PRCA) that begins after treatment with Epogen or other erythropoietin protein drugs [see WARNINGS AND PRECAUTIONS] Serious allergic reactions to Epogen [see WARNINGS AND PRECAUTIONS] Epogen from multiple-dose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and lactating women [see WARNINGS AND PRECAUTIONS, Use In Specific Populations]. | headache, body aches, diarrhea, cold symptoms (stuffy nose, sneezing, sore throat, cough), joint pain, bone pain, muscle pain or spasms, dizziness, depression, weight loss, sleep problems (insomnia), nausea, vomiting, trouble swallowing, or injection site reactions (pain, tenderness, or irritation). | Epogen is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Epogen is used to treat anemia caused by chemotherapy... | Epogen is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10935 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epogen | AMGEN INC | AMGEN INC | Intravenous; Subcutaneous | 10000 [iU]/1mL | Epogen is contraindicated in patients with: Uncontrolled hypertension [see WARNINGS AND PRECAUTIONS] Pure red cell aplasia (PRCA) that begins after treatment with Epogen or other erythropoietin protein drugs [see WARNINGS AND PRECAUTIONS] Serious allergic reactions to Epogen [see WARNINGS AND PRECAUTIONS] Epogen from multiple-dose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and lactating women [see WARNINGS AND PRECAUTIONS, Use In Specific Populations]. | headache, body aches, diarrhea, cold symptoms (stuffy nose, sneezing, sore throat, cough), joint pain, bone pain, muscle pain or spasms, dizziness, depression, weight loss, sleep problems (insomnia), nausea, vomiting, trouble swallowing, or injection site reactions (pain, tenderness, or irritation). | Epogen is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Epogen is used to treat anemia caused by chemotherapy... | Epogen is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10936 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Epogen | AMGEN INC | AMGEN INC | Intravenous; Subcutaneous | 20000 [iU]/1mL | Epogen is contraindicated in patients with: Uncontrolled hypertension [see WARNINGS AND PRECAUTIONS] Pure red cell aplasia (PRCA) that begins after treatment with Epogen or other erythropoietin protein drugs [see WARNINGS AND PRECAUTIONS] Serious allergic reactions to Epogen [see WARNINGS AND PRECAUTIONS] Epogen from multiple-dose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and lactating women [see WARNINGS AND PRECAUTIONS, Use In Specific Populations]. | headache, body aches, diarrhea, cold symptoms (stuffy nose, sneezing, sore throat, cough), joint pain, bone pain, muscle pain or spasms, dizziness, depression, weight loss, sleep problems (insomnia), nausea, vomiting, trouble swallowing, or injection site reactions (pain, tenderness, or irritation). | Epogen is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Epogen is used to treat anemia caused by chemotherapy... | Epogen is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10937 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eporatio | Ratiopharm Inc | Ratiopharm Inc | Intravenous; Subcutaneous | 1000 IU/0.5ml | NA | The most common side effects with Eporatio (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Eporatio, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Eporatio works in the body in the same way as the natural hormone to stimulate red-blood-cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Eporatio is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10938 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eporatio | Ratiopharm Inc | Ratiopharm Inc | Intravenous; Subcutaneous | 2000 IU/0.5ml | NA | The most common side effects with Eporatio (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Eporatio, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Eporatio works in the body in the same way as the natural hormone to stimulate red-blood-cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Eporatio is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10939 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eporatio | Ratiopharm Inc | Ratiopharm Inc | Intravenous; Subcutaneous | 3000 IU/0.5ml | NA | The most common side effects with Eporatio (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Eporatio, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Eporatio works in the body in the same way as the natural hormone to stimulate red-blood-cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Eporatio is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10940 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eporatio | Ratiopharm Inc | Ratiopharm Inc | Intravenous; Subcutaneous | 4000 IU/0.5ml | NA | The most common side effects with Eporatio (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Eporatio, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Eporatio works in the body in the same way as the natural hormone to stimulate red-blood-cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Eporatio is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10941 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eporatio | Ratiopharm Inc | Ratiopharm Inc | Intravenous; Subcutaneous | 5000 IU/0.5ml | NA | The most common side effects with Eporatio (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Eporatio, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Eporatio works in the body in the same way as the natural hormone to stimulate red-blood-cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Eporatio is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10942 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eporatio | Ratiopharm Inc | Ratiopharm Inc | Intravenous; Subcutaneous | 10000 IU/1.0ml | NA | The most common side effects with Eporatio (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Eporatio, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Eporatio works in the body in the same way as the natural hormone to stimulate red-blood-cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Eporatio is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10943 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eporatio | Ratiopharm Inc | Ratiopharm Inc | Intravenous; Subcutaneous | 20000 IU/1.0ml | NA | The most common side effects with Eporatio (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Eporatio, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Eporatio works in the body in the same way as the natural hormone to stimulate red-blood-cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Eporatio is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10944 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eporatio | Ratiopharm Inc | Ratiopharm Inc | Intravenous; Subcutaneous | 30000 IU/1.0ml | NA | The most common side effects with Eporatio (seen in between 1 and 10 patients in 100) are shunt thrombosis (clots that can form in blood vessels of patients on dialysis, a blood clearance technique), headache, hypertension (high blood pressure), hypertensive crisis (sudden, dangerously high blood pressure), skin reactions, arthralgia (joint pain) and influenza (flu)-like illness. | The active substance in Eporatio, epoetin theta, is a copy of a human hormone called erythropoietin that stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin theta in Eporatio works in the body in the same way as the natural hormone to stimulate red-blood-cell production. It is produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin theta. | Eporatio is used to treat anaemia (low levels of red blood cells or haemoglobin) that is causing symptoms. It is used in adults with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) and in adults with non-myeloid cancer (cancer not originating in the bone marrow) who are receiving chemotherapy (medicines to treat cancer). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10945 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 20000 unit / 0.5 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10946 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 30000 unit / 0.75 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10947 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 10000iu/1.0ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 10000 unit / mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10948 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 10000iu/ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 10000 unit / mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10949 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 1000iu/0.5ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 1000 unit / 0.5 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10950 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 20000iu/ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 20000 unit / mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10951 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 2000iu/0.5ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 2000 unit / 0.5 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10952 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 2000iu/ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 2000 unit / mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10953 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 3000iu/0.3ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 3000 unit / 0.3 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10954 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 40000iu/ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 40000 unit / mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10955 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 4000iu/0.4ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 4000 unit / 0.4 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10956 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 4000iu/ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 4000 unit / mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10957 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 5000iu/0.5ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 5000 unit / 0.5 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10958 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 6000 Iu/0.6 Ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 6000 unit / 0.6 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10959 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Eprex Sterile Solution 8000 Iu/0.8 Ml | Janssen Pharmaceuticals | Janssen Pharmaceuticals | Intravenous; Subcutaneous | 8000 unit / 0.8 mL | NA | headache joint or muscle aches, pain, or soreness nausea vomiting weight loss sores in the mouth difficulty falling asleep or staying asleep depression muscle spasms runny nose, sneezing, and congestion fever, cough, or chills redness, swelling, pain, or itching at the injection spot | Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery. | Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10960 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 50000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10961 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 500 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10962 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 2000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10963 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 3000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10964 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 5000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10965 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 10000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10966 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 20000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10967 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 4000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10968 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 6000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10969 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 30000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10970 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon Guard | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 10000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10971 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Neorecormon Guard | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | 30000 IU | NA | The types of side effects seen with NeoRecormon depend on the cause of the patient’s anaemia. The most common side effects (seen in between 1 and 10 patients in 100) are hypertension (high blood pressure), headache and thromboembolic events (formation of blood clots in the blood vessels). | The active substance in NeoRecormon, epoetin beta, is a copy of a human hormone called erythropoietin. Erythropoietin is produced by the kidneys and stimulates the production of red blood cells from the bone marrow. In patients receiving chemotherapy or with chronic renal failure, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. The epoetin beta in NeoRecormon works in the body in the same way as the natural hormone to stimulate red blood cell production. | NeoRecormon is used in the following situations: to treat anaemia (low red blood cell counts) that is causing symptoms in adults and children with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly); to prevent anaemia in premature babies; to treat anaemia that is causing symptoms in adults who are receiving chemotherapy for ‘non-myeloid’ cancer (cancer that does not affect the bone marrow); to increase the amount of blood that can be taken from adult patients with moderate anaemia who are going to have an operation and need to have a supply of their own blood before surgery (autologous blood transfusion).This is only done when blood storage procedures are not available or are insufficient because the surgery requires a large volume of blood. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 10972 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Physicians Total Care, Inc. | Physicians Total Care, Inc. | Intravenous; Subcutaneous | 10000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10973 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed K974by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Physicians Total Care, Inc. | Physicians Total Care, Inc. | Intravenous; Subcutaneous | 40000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10974 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Physicians Total Care, Inc. | Physicians Total Care, Inc. | Intravenous; Subcutaneous | 20000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10975 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Janssen Products, LP | Janssen Products, LP | Intravenous; Subcutaneous | 2000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10976 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Janssen Products, LP | Janssen Products, LP | Intravenous; Subcutaneous | 3000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10977 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Janssen Products, LP | Janssen Products, LP | Intravenous; Subcutaneous | 4000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10978 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Janssen Products, LP | Janssen Products, LP | Intravenous; Subcutaneous | 10000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10979 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Janssen Products, LP | Janssen Products, LP | Intravenous; Subcutaneous | 40000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10980 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Procrit | Janssen Products, LP | Janssen Products, LP | Intravenous; Subcutaneous | 20000 [iU]/1mL | PROCRIT is contraindicated in patients with: Uncontrolled hypertension Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT or other erythropoietin protein drugs. Serious allergic reactions to PROCRIT PROCRIT from multidose vials contains benzyl alcohol and is contraindicated in: Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with PROCRIT is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol | high blood pressure (hypertension), headache, joint pain, bone pain, muscle pain or spasms, body aches, nausea, vomiting, trouble swallowing, swelling, fatigue, dizziness, depression, diarrhea, weight loss, sleep problems (insomnia), pain/tenderness/irritation where Procrit is injected, or cold symptoms (stuffy nose, sneezing, cough, sore throat). | Procrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Procrit is used to treat anemia caused by chemotherapy... | Procrit is a prescription medicine used to treat the symptoms of Anemia caused by Chemotherapy, Chronic Kidney Disease and Zidovudine used to treat HIV (human immunodeficiency virus). Procrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10981 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Vifor (International) Inc. | Vifor (International) Inc. | Intravenous; Subcutaneous | 2000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10982 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Vifor (International) Inc. | Vifor (International) Inc. | Intravenous; Subcutaneous | 3000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10983 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Vifor (International) Inc. | Vifor (International) Inc. | Intravenous; Subcutaneous | 4000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10984 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Vifor (International) Inc. | Vifor (International) Inc. | Intravenous; Subcutaneous | 10000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10985 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Laboratories Div Pfizer Inc | Pfizer Laboratories Div Pfizer Inc | Intravenous; Subcutaneous | 2000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10986 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Laboratories Div Pfizer Inc | Pfizer Laboratories Div Pfizer Inc | Intravenous; Subcutaneous | 3000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10987 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Laboratories Div Pfizer Inc | Pfizer Laboratories Div Pfizer Inc | Intravenous; Subcutaneous | 4000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10988 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Laboratories Div Pfizer Inc | Pfizer Laboratories Div Pfizer Inc | Intravenous; Subcutaneous | 10000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10989 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Laboratories Div Pfizer Inc | Pfizer Laboratories Div Pfizer Inc | Intravenous; Subcutaneous | 40000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10990 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Vifor (International) Inc. | Vifor (International) Inc. | Intravenous; Subcutaneous | 20000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10991 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Laboratories Div Pfizer Inc | Pfizer Laboratories Div Pfizer Inc | Intravenous; Subcutaneous | 20000 [iU]/1mL | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10992 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 1000 IU/0.3ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10993 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 2000 IU/0.6ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10994 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 3000 IU/0.9ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10995 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 4000 IU/0.4ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10996 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 5000 IU/0.5ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10997 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 6000 IU/0.6ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10998 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 8000 IU/0.8ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 10999 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 10000 IU/1.0ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 11000 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 20000 IU/0.5ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 11001 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 30000 IU/0.75ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 11002 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Retacrit | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Intravenous; Subcutaneous | 40000 IU/1.0ml | RETACRIT is contraindicated in patients with: Uncontrolled hypertension. Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs. Serious allergic reactions to RETACRIT or other epoetin alfa products. | high blood pressure (hypertension), joint pain, muscle spasm or pain, fever, dizziness, medical device malfunction, blockage of a blood vessel, upper respiratory tract infection, cough, rash, injection site irritation or pain, nausea, vomiting, swelling and sores inside the mouth, weight loss, low white blood cell count (leukopenia), bone pain, high blood sugar (hyperglycemia), insomnia, headache, depression, difficulty swallowing, low blood potassium, blood clots and deep vein thrombosis DVTs), itching, and chills | Retacrit is a man-made form of a protein that helps your body produce red blood cells. This protein may be reduced when you have kidney failure or use certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Retacrit is used to treat anemia caused by chemotherapy... | Retacrit is a prescription medicine used to treat the symptoms of Chronic Kidney Disease-Associated Anemia, Zidovudine-Related Anemia, Chemotherapy-Related Anemia and Reduction of Allogenic Red Blood Cell Transfusions in patient undergoing elective, noncardiac, nonvascular surgery. Retacrit may be used alone or with other medications. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | Epoetin alfa-epbx is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. | Link | Link | NA |
| 11003 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 1000 IU/0.3ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11004 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 2000 IU/0.6ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11005 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 3000 IU/0.9ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11006 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 4000 IU/0.4ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11007 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 5000 IU/0.5ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11008 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 6000 IU/0.6ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11009 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 8000 IU/0.8ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11010 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 10000 IU/1.0ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11011 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 20000 IU/0.5ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11012 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 30000 IU/0.75ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11013 | Th1240 | Erythropoietin | >Th1240_Erythropoietin APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR | 18396.1 | C815H1317N233O241S5 | 8.75 | NA | 53 °C | **Healthy volunteers:** The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection [F85]. A half-life of approximately 6 hours has been reported in children [F85]., **Adult and paediatric patients with CRF:** The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis [FDA Label]. , **Cancer patients receiving cyclic chemotherapy:** Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours [FDA Label]. | Erythropoietin (EPO) is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow [FDA Label]. Epoetin alfa (Epoge) was developed by Amgen Inc. in 1983 as the first rhEPO commercialized in the United States, followed by other alfa and beta formulations. Epoetin alfa is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology and is used for the treatment of patients with anemia associated with various clinical conditions, such as chronic renal failure, antiviral drug therapy, chemotherapy, or a high risk for perioperative blood loss from surgical procedures [FDA Label]. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin and has the same biological activity as the endogenous erythropoietin. Epoetin alfa biosimilar, such as Retacrit (epoetin alfa-epbx or epoetin zeta), has been formulated to allow more access to treatment options for patients in the market [L2784]. The biosimilar is approved by the FDA and EMA as a safe, effective and affordable biological product and displays equivalent clinical efficacy, potency, and purity to the reference product [A7504]. Epoetin alfa formulations can be administered intravenously or subcutaneously. | Indicated in adult and paediatric patients for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, treatment of anemia due to zidovudine in patients with HIV-infection, treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy, reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. | Erythropoietin and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [F85]. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly [F85]. Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks [FDA Label]. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy [FDA Label]. | Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways [A33079]. The affinity (Kd) of EPO for its receptor on human cells is ~100 to 200 pM [A33080]. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins [A33079]. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x [A33079]. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C- | Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label [FDA Label]. | Binding of erythropoietin and epoetin alfa to EPO-R leads to cellular internalization, which involves the degradation of the ligand. Erythropoietin and epoetin alfa may also be degraded by the reticuloendothelial scavenging pathway or lymphatic system [A33080]. | The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) [A33080, L85]. The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% [A33080, L85]. **Adult and paediatric patients with CRF:** Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours [FDA Label]. **Cancer patients receiving cyclic chemotherapy:** The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen [FDA Label]. | In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution [A33080, A33076]. | **Healthy volunteers: ** In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg [A33076]. **Cancer patients receiving cyclic chemotherapy:** The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing [FDA Label]. The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) [FDA Label]. | NA | NA | NA | NA | NA | Erythropoietin receptor | Silapo | Stada Arzneimittel Ag | Stada Arzneimittel Ag | Intravenous; Subcutaneous | 40000 IU/1.0ml | NA | The most common side effects with Silapo (which may affect more than 1 in 100 people) are headache and increased blood pressure. | Silapo contains the active substance epoetin zeta and is a ‘biosimilar’ medicine. This means that Silapo is highly similar to another biological medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. | to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, decreasing ability of the kidneys to work properly) or other kidney problems; to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions; to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery; to reduce the need for blood transfusions in adults with moderate anaemia who are about to have major orthopaedic (bone) surgery, such as hip surgery. It is used in patients with normal blood iron levels who could experience complications from a blood transfusion, if they do not donate their own blood before surgery and are expected to lose 900 to 1,800 ml of blood; to treat anaemia in adults with myelodysplastic syndromes (conditions in which the production of healthy blood cells is defective). Silapo is used when patients are at low or intermediate risk of developing acute myeloid leukaemia and have low levels of the natural hormone erythropoietin. | potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol | NA | Link | Link | NA |
| 11372 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Adjuvants, Immunologic | 2172664 | 03-10-2000 | 26-03-2016 | Denosumab,Etanercept,Peginterferon alfa-2a,Interferon alfa-n1,Interferon alfa-n3,Peginterferon alfa-2b,Anakinra,Interferon gamma-1b,Adalimumab,Gemtuzumab ozogamicin,Pegaspargase,Infliximab,Interferon beta-1b,Interferon alfacon-1,Rituximab,Basiliximab,Muromonab,Ibritumomab tiuxetan,Tositumomab,Alemtuzumab,Alefacept,Efalizumab,Antithymocyte immunoglobulin (rabbit),Interferon alfa-2b,Daclizumab,Phenylalanine,Flunisolide,Bortezomib,Cladribine,Carmustine,Amsacrine,Bleomycin,Chlorambucil,Raltitrexed,Mitomycin,Bexarotene,Vindesine,Floxuridine,Indomethacin,Tioguanine,Vinorelbine,Dexrazoxane,Beclomethasone dipropionate,Sorafenib,Streptozocin,Trifluridine,Gemcitabine,Betamethasone,Teniposide,Epirubicin,Chloramphenicol,Lenalidomide,Altretamine,Zidovudine,Cisplatin,Oxaliplatin,Cyclophosphamide,Vincristine,Fluorouracil,Propylthiouracil,Pentostatin,Methotrexate,Carbamazepine,Vinblastine,Fluticasone propionate,Fluocinolone acetonide,Linezolid,Imatinib,Triamcinolone,Clofarabine,Prednisone,Pemetrexed,Fludrocortisone,Mycophenolate mofetil,Daunorubicin,Tretinoin,Irinotecan,Methimazole,Etoposide,Sulfasalazine,Dacarbazine,Temozolomide,Penicillamine,Prednisolone,Sirolimus,Mechlorethamine,Azacitidine,Carboplatin,Methylprednisolone,Dactinomycin,Cytarabine,Azathioprine,Doxorubicin,Hydroxyurea,Busulfan,Mycophenolic acid,Topotecan,Mercaptopurine,Thalidomide,Melphalan,Fludarabine,Flucytosine,Capecitabine,Trilostane,Procarbazine,Arsenic trioxide,Idarubicin,Ifosfamide,Estramustine,Mitoxantrone,Lomustine,Budesonide,Paclitaxel,Dexamethasone,Docetaxel,Dasatinib,Eculizumab,Decitabine,Sunitinib,Nelarabine,Abatacept,Corticotropin,Cortisone acetate,Paramethasone,Ciclesonide,Stepronin,Everolimus,Hydroxychloroquine,Castanospermine,Vorinostat,2-Methoxyethanol,Brequinar,Thiotepa,Aldosterone,Ixabepilone,Nilotinib,Pirfenidone,Afelimomab,Belinostat,Trabectedin,Interferon alfa,Glatiramer,Gallium nitrate,Briakinumab,Human interferon omega-1,Apremilast,Trastuzumab emtansine,Canakinumab,Tocilizumab,Temsirolimus,Rilonacept,Pazopanib,Panobinostat,Mepolizumab,Bosutinib,Abetimus,Golimumab,Belatacept,Bendamustine,Cabazitaxel,Pralatrexate,Wortmannin,Brentuximab vedotin,Eribulin,Ruxolitinib,Belimumab,Teriflunomide,Carfilzomib,Ponatinib,Certolizumab pegol,Fluticasone furoate,Dimethyl fumarate,Pomalidomide,Obinutuzumab,Fluprednidene,Secukinumab,Vedolizumab,Siltuximab,Blinatumomab,Ibrutinib,Idelalisib,Palbociclib,Olaparib,Dinutuximab,Vilanterol,Tixocortol,Peginterferon beta-1a,Antilymphocyte immunoglobulin (horse),Fluprednisolone,Meprednisone,Tepoxalin,Dexamethasone isonicotinate,Melengestrol,Ixekizumab,Ravulizumab,Pirarubicin,Voclosporin,Peficitinib,Sarilumab,Brodalumab,Sirukumab,Baricitinib,Guselkumab,Deflazacort,Ocrelizumab,Triptolide,Siponimod,Ozanimod,Mizoribine,Gusperimus,Cepeginterferon alfa-2B,Trofosfamide,Doxifluridine,Deoxyspergualin,Acteoside,Cortivazol,Hypericin,9-(N-methyl-L-isoleucine)-cyclosporin A,Prednylidene,Fluocortin,Begelomab,Fluperolone,Cloprednol,Fluclorolone,Fluticasone,Tetrandrine,Monomethyl fumarate,Mometasone furoate,Hydrocortisone acetate,Hydrocortisone succinate,Emapalumab,Risankizumab,Rozanolixizumab,Bleselumab,Clobetasol propionate,Fluocinonide,Hydrocortisone butyrate,Desoximetasone,Mometasone,Fluocortolone,Fluorometholone,Difluocortolone,Upadacitinib,Ponesimod,Lexacalcitol,Inolimomab,Fasitibant,Natalizumab,Pimecrolimus,Roflumilast,Sipuleucel-T,Aldesleukin,Clozapine,Methadone,Ribavirin,Zolmitriptan,Sulfamethoxazole,Telbivudine,Leflunomide,Tofacitinib,Trastuzumab,Fingolimod,Tacrolimus,Caffeine,Dyphylline,Pentoxifylline,Oxtriphylline,Theobromine,Fenethylline,8-azaguanine,7,9-Dimethylguanine,Xanthine,7-Deazaguanine,Guanine,9-Methylguanine,Peldesine,Hypoxanthine,9-Deazaguanine,Propentofylline,Valomaciclovir,3-isobutyl-1-methyl-7H-xanthine,Uric acid,Doxofylline,6-O-benzylguanine,Lisofylline,Lobucavir,Cafedrine,Theodrenaline,Bamifylline,Proxyphylline,Acefylline,Etamiphylline,Pentifylline,Bufylline,Bromotheophylline,Furafylline,8-chlorotheophylline,PCS-499,G17DT,PEV3A,INGN 225,Rindopepimut,SRP 299,GI-5005,Vitespen,TG4010,Anthrax immune globulin human,Rabies virus inactivated antigen, B,Haemophilus influenzae type B strain 1482 capsular polysaccharide tetanus toxoid conjugate antigen,Rotavirus vaccine,Rabies virus inactivated antigen, A,Haemophilus influenzae type B capsular polysaccharide meningococcal outer membrane protein conjugate antigen,Clostridium tetani toxoid antigen (formaldehyde inactivated),Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated),Influenza A virus A/California/7/2009 X-181 (H1N1) antigen (propiolactone inactivated),Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated),Influenza B virus B/Brisbane/60/2008 antigen (formaldehyde inactivated),Typhoid Vi polysaccharide vaccine,Hepatitis A Vaccine,Haemophilus influenzae type B strain 20752 capsular polysaccharide tetanus toxoid conjugate antigen,Influenza A virus A/Brisbane/59/2007(H1N1) hemagglutinin antigen (propiolactone inactivated),Influenza B virus B/Brisbane/60/2008 hemagglutinin antigen (propiolactone inactivated),Influenza A virus A/California/7/2009 X-181 (H1N1) hemagglutinin antigen (propiolactone inactivated),Influenza B virus B/Brisbane/60/2008 antigen (propiolactone inactivated),Rabies immune globulin, human,Hepatitis B Vaccine (Recombinant),Tecemotide,Typhoid vaccine,Influenza A virus A/Victoria/210/2009 X-187 (H3N2) hemagglutinin antigen (formaldehyde inactivated),Influenza B virus B/Brisbane/60/2008 hemagglutinin antigen (formaldehyde inactivated),Influenza A virus A/California/7/2009 (H1N1) live (attenuated) antigen,Influenza A virus A/Victoria/210/2009 X-187 (H3N2) antigen (formaldehyde inactivated),Influenza A virus A/Perth/16/2009 (H3N2) live (attenuated) antigen,Influenza A virus A/Uruguay/716/2007(H3N2) antigen (propiolactone inactivated),Influenza A virus A/Brisbane/59/2007(H1N1) antigen (propiolactone inactivated),Smallpox (Vaccinia) Vaccine, Live,Pertussis vaccine,Yersinia pestis 195/p antigen (formaldehyde inactivated),Varicella zoster vaccine (recombinant),Modified vaccinia ankara,Ebola Zaire vaccine (live, attenuated),Moderna COVID-19 Vaccine,Measles virus vaccine live attenuated,Abciximab,Eptifibatide,Ticlopidine,Tirofiban,Acetylsalicylic acid,Dipyridamole,Iloprost,Sulfinpyrazone,Ridogrel,Sevoflurane,Epoprostenol,Nimesulide,Tesmilifene,Defibrotide,Beraprost,Ibudilast,Andrographolide,Caplacizumab,Prasugrel,Cangrelor,Tranilast,Triflusal,Ticagrelor,Icosapent ethyl,Vorapaxar,Trapidil,Naftopidil,Sarpogrelate,Ifetroban,Nitroaspirin,Ketanserin,Indobufen,Butylphthalide,Hydroxytyrosol,Ramatroban,Picotamide,Cloricromen,Linsidomine,Buflomedil,Relcovaptan,Maritime pine extract,Resveratrol,Lipegfilgrastim,Rubella virus vaccine,Varicella zoster vaccine (live/attenuated),Bacillus calmette-guerin substrain tice live antigen,Bacillus calmette-guerin substrain connaught live antigen,Yellow fever vaccine,Anthrax vaccine,Typhoid Vaccine Live,Bacillus calmette-guerin substrain danish 1331 live antigen,BCG vaccine,Human adenovirus e serotype 4 strain cl-68578 antigen,Vibrio cholerae CVD 103-HgR strain live antigen,Adenovirus type 7 vaccine live,Palifermin,Fluvoxamine,Betaxolol,Disopyramide,Lidocaine,Conjugated estrogens,Ropivacaine,Acetaminophen,Olanzapine,Chlorzoxazone,Grepafloxacin,Mirtazapine,Mexiletine,Tacrine,Triamterene,Promazine,Zolpidem,Entecavir,Nabumetone,Quinine,Fluoxetine,Chlorpromazine,Flutamide,Haloperidol,Albendazole,Rofecoxib,Cinnarizine,Propranolol,Diclofenac,Guanabenz,Verapamil,Paroxetine,Thiabendazole,Riluzole,Zileuton,Clopidogrel,Estradiol,Acyclovir,Naproxen,Trifluoperazine,Perphenazine,Terbinafine,Ranitidine,Ethanol,Maprotiline,Alosetron,Lomefloxacin,Ramelteon,Frovatriptan,Levobupivacaine,Cinacalcet,Selegiline,Tocainide,Praziquantel,Melatonin,Primaquine,Hesperetin,Nifedipine,Carvedilol,Cilostazol,Propafenone,Domperidone,Dexfenfluramine,Rasagiline,Temafloxacin,Aminophenazone,Antipyrine,Bromazepam,Thiothixene,Etoricoxib,Genistein,Phenacetin,Estrone sulfate,Flunarizine,Lorcaserin,Lofexidine,Mianserin,Eltrombopag,Asenapine,Vadimezan,Dapagliflozin,Agomelatine,Benzyl alcohol,Capsaicin,(R)-warfarin,Perampanel,Tasimelteon,Stiripentol,Zotepine,Propacetamol,Ramosetron,Binimetinib,Voxilaprevir,Triclabendazole,Rucaparib,Dihydralazine,Estradiol acetate,Estradiol benzoate,Estradiol cypionate,Estradiol dienanthate,Estradiol valerate,Istradefylline,Azelastine,Efavirenz,Metoclopramide,Bicifadine,GTS-21,Flecainide,Ethinylestradiol,Amitriptyline,Doxepin,Mephenytoin,Cyclobenzaprine,Selumetinib,Penciclovir,Fenfluramine,Mefenamic acid,Ondansetron,Methylene blue,Benzocaine,Theophylline,Warfarin,Tizanidine,Pimozide,Aminophylline,Acenocoumarol,Anagrelide,Erlotinib,Axitinib,Tegafur,Enasidenib,Tamoxifen,Imipramine,Clonidine,Clomipramine,Lepirudin,Bivalirudin,Alteplase,Urokinase,Reteplase,Anistreplase,Tenecteplase,Drotrecogin alfa,Streptokinase,Dicoumarol,Argatroban,Ardeparin,Phenindione,Fondaparinux,Pentosan polysulfate,Phenprocoumon,Heparin,Enoxaparin,4-hydroxycoumarin,Coumarin,Ximelagatran,Desmoteplase,Ancrod,Fibrinolysin,Rivaroxaban,Sulodexide,Semuloparin,Idraparinux,Astaxanthin,Apixaban,Otamixaban,Amediplase,Dabigatran etexilate,Danaparoid,Dalteparin,Tinzaparin,Ferulic acid,Ethyl biscoumacetate,Nadroparin,Ditazole,Edoxaban,Potassium citrate,Sodium citrate,Dextran,Bemiparin,Parnaparin,Desirudin,Zinc citrate,Antithrombin Alfa,Protein C,Antithrombin III human,Letaxaban,Darexaban,Betrixaban,Nafamostat,Monteplase,Gabexate,Fluindione,Protein S human,Brinase,Clorindione,Diphenadione,Tioclomarol,Melagatran,Saruplase,(S)-Warfarin,Tocopherylquinone,Edetate calcium disodium anhydrous,Dabigatran,Troxerutin,Edetic acid,Reviparin,Dermatan sulfate,SR-123781A,Dociparstat sodium,Methyclothiazide,Bendroflumethiazide,Benzthiazide,Cyclothiazide,Hydroflumethiazide,Chlorothiazide,Hydrochlorothiazide,Trichlormethiazide,Polythiazide,Mebutizide,Cyclopenthiazide,Buthiazide,Tedizolid phosphate,Cyclosporine,Ropinirole,Cyanocobalamin,Allopurinol,Magnesium,Lopinavir,Inebilizumab,Flupentixol,Bacillus calmette-guerin substrain russian BCG-I live antigen,Fexinidazole,Allogeneic processed thymus tissue,Tick-borne encephalitis vaccine (whole virus, inactivated),Ropeginterferon alfa-2b,Nuvaxovid | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon A Soln Inj 6 Million | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 6000000 unit / mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11373 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Alfa Interferons | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon A Sterile Pws 18m Unit/vial | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 18000000 unit / vial | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11374 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Antineoplastic and Immunomodulating Agents | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon A Sterile Pws 3m Unit/vial | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 3000000 unit / vial | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11375 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Cancer immunotherapy | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon A Sterile Pws 9m Unit/vial | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 9000000 unit / vial | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11376 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Cytochrome P-450 CYP1A2 Inhibitors | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A | Genentech, Inc. | Genentech, Inc. | Subcutaneous | 11.1 ug/0.5mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | Alpheon is a solution for injection that contains the active substance interferon alfa-2a. | Roferon-A (interferon alfa-2a, recombinant) is indicated for the treatment of chronic hepatitis C and hairy cell leukemia in patients 18 years of age or older. In addition, it is indicated for chronic phase, Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) patients who are minimally pretreated (within 1 year of diagnosis). | NA | NA | Link | Link | NA |
| 11377 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Cytochrome P-450 CYP1A2 Inhibitors (strength unknown) | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A | Genentech, Inc. | Genentech, Inc. | Subcutaneous | 22.2 ug/0.5mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | Alpheon is a solution for injection that contains the active substance interferon alfa-2a. | Roferon-A (interferon alfa-2a, recombinant) is indicated for the treatment of chronic hepatitis C and hairy cell leukemia in patients 18 years of age or older. In addition, it is indicated for chronic phase, Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) patients who are minimally pretreated (within 1 year of diagnosis). | NA | NA | Link | Link | NA |
| 11378 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Cytochrome P-450 Enzyme Inhibitors | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A | Genentech, Inc. | Genentech, Inc. | Subcutaneous | 33.3 ug/0.5mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | Alpheon is a solution for injection that contains the active substance interferon alfa-2a. | Roferon-A (interferon alfa-2a, recombinant) is indicated for the treatment of chronic hepatitis C and hairy cell leukemia in patients 18 years of age or older. In addition, it is indicated for chronic phase, Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) patients who are minimally pretreated (within 1 year of diagnosis). | NA | NA | Link | Link | NA |
| 11379 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Immunosuppressive Agents | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A Sol Inj 3million Iu/vial | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 3000000 unit / mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11380 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Immunotherapy | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A Soln-liq Im Sc 4.5million I.u/ml | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 4500000 IU/mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11381 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Interferon alpha | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A Soln-liq Im Sc 9million I.U./ml | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 9000000 IU/ml | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11382 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Interferons | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A Solution 18 Million I.U./3ml | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 18000000 IU/3mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11383 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | Myelosuppressive Agents | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A Solution 3 Million I.U./ml | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 3 m / mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11384 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | NA | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A Solution 6 Million I.U./ml | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 6000000 IU/mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11385 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | NA | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A Solution Inj 36000000unit/ml | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 36000000 unit / mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 11386 | Th1245 | Interferon alfa-2a | >Th1245_Interferon_alfa-2a CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE | 19241.1 | C860H1353N227O255S9 | 5.99 | -0.336 | NA | The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours). | Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences. | For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection. | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R. | Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. | Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair. | NA | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. | * 0.223 to 0.748 L/kg [healthy people] | * 2.14 - 3.62 mL/min/kg [healthy] | NA | NA | NA | NA | NA | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 | Roferon-A Solution Inj. 9million I.U./0.9ml | Hoffmann La Roche | Hoffmann La Roche | Intramuscular; Subcutaneous | 9000000 unit / .9 mL | Roferon-A (interferon alfa-2a, recombinant) is contraindicated in patients with: Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components Autoimmune hepatitis Hepatic decompensation (Child-Pugh class B and C) before or during treatment Roferon-A (interferon alfa-2a, recombinant) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal. | lu like symptoms such as fatigue (58% to 95%), fever (25% to 92%), myalgia (68% to 71%), headache (44% to 66%), chills (23% to 64%), arthralgia/bone pain (25% to 47%), asthenia (6%), sweating (5%), leg cramps (3%), and malaise (1%). Weight loss (25% to 33%), change in taste or smell (3% to 25%), pain (24%), back pain (16%), night sweats (8%), menstrual irregularity (4%), reversible hearing loss, and tinnitus have also been reported | NA | NA | NA | NA | Link | Link | NA |
| 12026 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12027 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Antibodies | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12028 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Antineoplastic Agents | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12029 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Antineoplastic Agents, Immunological | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12030 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Blood Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12031 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Globulins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12032 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Immunoglobulins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12033 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Immunoproteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12034 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12035 | Th1279 | Bavituximab | >Th1279_Bavituximab EVQLQQSGPELEKPGASVKLSCKASGYSFTGYNMNWVKQSHGKSLEWIGHIDPYYGDTSYNQKFRGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCVKGGYYGHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 30 Hrs | Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4. | Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), HIV infection, hepatitis (viral, C), and solid tumors. | NA | Bavituximab Anti-Cancer is a monoclonal antibody that binds to a basic component of the cell structure called a phospholipid that is exposed only on the surface of tumor blood vessel cells or on cells infected with certain viruses. Bavituximab binding to the tumor blood vessel cells alerts the body’s immune system to attack the tumor and its blood supply. This has been shown to inhibit tumor growth and development. Because in healthy cells the phospholipids are concealed inside the cell, the bavituximab does not bind to them. This targets the bavituximab to the malignant cells and potentially minimizes unwanted side effects. Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant. After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity. Bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta. Stimulating an immune response is a key proposed anti-viral mechanism of action of bavituximab. | Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab | NA | NA | NA | NA | Serum Globulins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12181 | Th1296 | Ciliary neurotrophic factor | >Th1296_Ciliary_neurotrophic_factor MAFTEHSPLTPHRRDLCSRSIWLARKIRSDLTALTESYVKHQGLNKNINLDSADGMPVASTDQWSELTEAERLQENLQAYRTFHVLLARLLEDQQVHFTPTEGDFHQAIHTLLLQVAAFAYQIEELMILLEYKIPRNEADGMPINVGDGGLFEKKLWGLKVLQELSQWTVRSIHDLRFISSHQTGIPARGSHYIANNKKM | NA | NA | NA | NA | NA | NA | Ciliary neurotrophic factor (NT-501) is Neurotech's lead product which is in two Phase II/III clinical trials for the treatment of visual loss associated with retinitis pigmentosa and a Phase II trial for the treatment of the dry form of age-related macular degeneration. Neurotech is also evaluating other factors that can be used with its proprietary delivery technology, Encapsulated Cell Technology (ECT), to treat additional retinal diseases. | Investigated for use/treatment in eye disorders/infections, macular degeneration, and retinal disorders (unspecified). | NA | NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, Ciliary Neurotrophic Factor (CNTF), directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT). | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12182 | Th1296 | Ciliary neurotrophic factor | >Th1296_Ciliary_neurotrophic_factor MAFTEHSPLTPHRRDLCSRSIWLARKIRSDLTALTESYVKHQGLNKNINLDSADGMPVASTDQWSELTEAERLQENLQAYRTFHVLLARLLEDQQVHFTPTEGDFHQAIHTLLLQVAAFAYQIEELMILLEYKIPRNEADGMPINVGDGGLFEKKLWGLKVLQELSQWTVRSIHDLRFISSHQTGIPARGSHYIANNKKM | NA | NA | NA | NA | NA | NA | Ciliary neurotrophic factor (NT-501) is Neurotech's lead product which is in two Phase II/III clinical trials for the treatment of visual loss associated with retinitis pigmentosa and a Phase II trial for the treatment of the dry form of age-related macular degeneration. Neurotech is also evaluating other factors that can be used with its proprietary delivery technology, Encapsulated Cell Technology (ECT), to treat additional retinal diseases. | Investigated for use/treatment in eye disorders/infections, macular degeneration, and retinal disorders (unspecified). | NA | NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, Ciliary Neurotrophic Factor (CNTF), directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT). | NA | NA | NA | NA | NA | Biological Factors | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12183 | Th1296 | Ciliary neurotrophic factor | >Th1296_Ciliary_neurotrophic_factor MAFTEHSPLTPHRRDLCSRSIWLARKIRSDLTALTESYVKHQGLNKNINLDSADGMPVASTDQWSELTEAERLQENLQAYRTFHVLLARLLEDQQVHFTPTEGDFHQAIHTLLLQVAAFAYQIEELMILLEYKIPRNEADGMPINVGDGGLFEKKLWGLKVLQELSQWTVRSIHDLRFISSHQTGIPARGSHYIANNKKM | NA | NA | NA | NA | NA | NA | Ciliary neurotrophic factor (NT-501) is Neurotech's lead product which is in two Phase II/III clinical trials for the treatment of visual loss associated with retinitis pigmentosa and a Phase II trial for the treatment of the dry form of age-related macular degeneration. Neurotech is also evaluating other factors that can be used with its proprietary delivery technology, Encapsulated Cell Technology (ECT), to treat additional retinal diseases. | Investigated for use/treatment in eye disorders/infections, macular degeneration, and retinal disorders (unspecified). | NA | NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, Ciliary Neurotrophic Factor (CNTF), directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT). | NA | NA | NA | NA | NA | Intercellular Signaling Peptides and Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12184 | Th1296 | Ciliary neurotrophic factor | >Th1296_Ciliary_neurotrophic_factor MAFTEHSPLTPHRRDLCSRSIWLARKIRSDLTALTESYVKHQGLNKNINLDSADGMPVASTDQWSELTEAERLQENLQAYRTFHVLLARLLEDQQVHFTPTEGDFHQAIHTLLLQVAAFAYQIEELMILLEYKIPRNEADGMPINVGDGGLFEKKLWGLKVLQELSQWTVRSIHDLRFISSHQTGIPARGSHYIANNKKM | NA | NA | NA | NA | NA | NA | Ciliary neurotrophic factor (NT-501) is Neurotech's lead product which is in two Phase II/III clinical trials for the treatment of visual loss associated with retinitis pigmentosa and a Phase II trial for the treatment of the dry form of age-related macular degeneration. Neurotech is also evaluating other factors that can be used with its proprietary delivery technology, Encapsulated Cell Technology (ECT), to treat additional retinal diseases. | Investigated for use/treatment in eye disorders/infections, macular degeneration, and retinal disorders (unspecified). | NA | NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, Ciliary Neurotrophic Factor (CNTF), directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT). | NA | NA | NA | NA | NA | Nerve Growth Factors | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12185 | Th1296 | Ciliary neurotrophic factor | >Th1296_Ciliary_neurotrophic_factor MAFTEHSPLTPHRRDLCSRSIWLARKIRSDLTALTESYVKHQGLNKNINLDSADGMPVASTDQWSELTEAERLQENLQAYRTFHVLLARLLEDQQVHFTPTEGDFHQAIHTLLLQVAAFAYQIEELMILLEYKIPRNEADGMPINVGDGGLFEKKLWGLKVLQELSQWTVRSIHDLRFISSHQTGIPARGSHYIANNKKM | NA | NA | NA | NA | NA | NA | Ciliary neurotrophic factor (NT-501) is Neurotech's lead product which is in two Phase II/III clinical trials for the treatment of visual loss associated with retinitis pigmentosa and a Phase II trial for the treatment of the dry form of age-related macular degeneration. Neurotech is also evaluating other factors that can be used with its proprietary delivery technology, Encapsulated Cell Technology (ECT), to treat additional retinal diseases. | Investigated for use/treatment in eye disorders/infections, macular degeneration, and retinal disorders (unspecified). | NA | NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, Ciliary Neurotrophic Factor (CNTF), directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT). | NA | NA | NA | NA | NA | Nerve Tissue Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12186 | Th1296 | Ciliary neurotrophic factor | >Th1296_Ciliary_neurotrophic_factor MAFTEHSPLTPHRRDLCSRSIWLARKIRSDLTALTESYVKHQGLNKNINLDSADGMPVASTDQWSELTEAERLQENLQAYRTFHVLLARLLEDQQVHFTPTEGDFHQAIHTLLLQVAAFAYQIEELMILLEYKIPRNEADGMPINVGDGGLFEKKLWGLKVLQELSQWTVRSIHDLRFISSHQTGIPARGSHYIANNKKM | NA | NA | NA | NA | NA | NA | Ciliary neurotrophic factor (NT-501) is Neurotech's lead product which is in two Phase II/III clinical trials for the treatment of visual loss associated with retinitis pigmentosa and a Phase II trial for the treatment of the dry form of age-related macular degeneration. Neurotech is also evaluating other factors that can be used with its proprietary delivery technology, Encapsulated Cell Technology (ECT), to treat additional retinal diseases. | Investigated for use/treatment in eye disorders/infections, macular degeneration, and retinal disorders (unspecified). | NA | NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, Ciliary Neurotrophic Factor (CNTF), directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT). | NA | NA | NA | NA | NA | Peptides | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12187 | Th1296 | Ciliary neurotrophic factor | >Th1296_Ciliary_neurotrophic_factor MAFTEHSPLTPHRRDLCSRSIWLARKIRSDLTALTESYVKHQGLNKNINLDSADGMPVASTDQWSELTEAERLQENLQAYRTFHVLLARLLEDQQVHFTPTEGDFHQAIHTLLLQVAAFAYQIEELMILLEYKIPRNEADGMPINVGDGGLFEKKLWGLKVLQELSQWTVRSIHDLRFISSHQTGIPARGSHYIANNKKM | NA | NA | NA | NA | NA | NA | Ciliary neurotrophic factor (NT-501) is Neurotech's lead product which is in two Phase II/III clinical trials for the treatment of visual loss associated with retinitis pigmentosa and a Phase II trial for the treatment of the dry form of age-related macular degeneration. Neurotech is also evaluating other factors that can be used with its proprietary delivery technology, Encapsulated Cell Technology (ECT), to treat additional retinal diseases. | Investigated for use/treatment in eye disorders/infections, macular degeneration, and retinal disorders (unspecified). | NA | NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, Ciliary Neurotrophic Factor (CNTF), directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT). | NA | NA | NA | NA | NA | Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12214 | Th1299 | QS-21 | NA | 1990.1319 | C92H148O46 | NA | NA | NA | NA | QS-21 is an investigational adjuvant, which is a substance added to vaccines and other immunotherapies that is designed to enhance the body’s immune response to the antigen contained within the treatment. It is the leading member of the Stimulon family of adjuvants. As a vaccine additive, it is currently being evaluated in clinical trials in a variety of disease areas by Antigenics. | Investigated for use/treatment in genital herpes, HIV infection, hepatitis (viral, B), influenza, malaria, melanoma, and viral infection. | NA | QS-21 has the potential ability to increase total vaccine-specific antibody response and T-cell response. In addition, QS-21 appears to increase potency of the vaccine with relatively small quantities of antigen and to exhibit synergy with other adjuvants. Because of the ability of QS-21 to improve the body’s immune response to very low doses of antigen, vaccine antigen may be ‘spared,’ which could significantly decrease the amount of antigen required for a given dose and make vaccine production more economical. | NA | NA | NA | NA | NA | Adjuvants, Immunologic | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12215 | Th1299 | QS-21 | NA | 1990.1319 | C92H148O46 | NA | NA | NA | NA | QS-21 is an investigational adjuvant, which is a substance added to vaccines and other immunotherapies that is designed to enhance the body’s immune response to the antigen contained within the treatment. It is the leading member of the Stimulon family of adjuvants. As a vaccine additive, it is currently being evaluated in clinical trials in a variety of disease areas by Antigenics. | Investigated for use/treatment in genital herpes, HIV infection, hepatitis (viral, B), influenza, malaria, melanoma, and viral infection. | NA | QS-21 has the potential ability to increase total vaccine-specific antibody response and T-cell response. In addition, QS-21 appears to increase potency of the vaccine with relatively small quantities of antigen and to exhibit synergy with other adjuvants. Because of the ability of QS-21 to improve the body’s immune response to very low doses of antigen, vaccine antigen may be ‘spared,’ which could significantly decrease the amount of antigen required for a given dose and make vaccine production more economical. | NA | NA | NA | NA | NA | Carbohydrates | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12216 | Th1299 | QS-21 | NA | 1990.1319 | C92H148O46 | NA | NA | NA | NA | QS-21 is an investigational adjuvant, which is a substance added to vaccines and other immunotherapies that is designed to enhance the body’s immune response to the antigen contained within the treatment. It is the leading member of the Stimulon family of adjuvants. As a vaccine additive, it is currently being evaluated in clinical trials in a variety of disease areas by Antigenics. | Investigated for use/treatment in genital herpes, HIV infection, hepatitis (viral, B), influenza, malaria, melanoma, and viral infection. | NA | QS-21 has the potential ability to increase total vaccine-specific antibody response and T-cell response. In addition, QS-21 appears to increase potency of the vaccine with relatively small quantities of antigen and to exhibit synergy with other adjuvants. Because of the ability of QS-21 to improve the body’s immune response to very low doses of antigen, vaccine antigen may be ‘spared,’ which could significantly decrease the amount of antigen required for a given dose and make vaccine production more economical. | NA | NA | NA | NA | NA | Glycosides | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12217 | Th1299 | QS-21 | NA | 1990.1319 | C92H148O46 | NA | NA | NA | NA | QS-21 is an investigational adjuvant, which is a substance added to vaccines and other immunotherapies that is designed to enhance the body’s immune response to the antigen contained within the treatment. It is the leading member of the Stimulon family of adjuvants. As a vaccine additive, it is currently being evaluated in clinical trials in a variety of disease areas by Antigenics. | Investigated for use/treatment in genital herpes, HIV infection, hepatitis (viral, B), influenza, malaria, melanoma, and viral infection. | NA | QS-21 has the potential ability to increase total vaccine-specific antibody response and T-cell response. In addition, QS-21 appears to increase potency of the vaccine with relatively small quantities of antigen and to exhibit synergy with other adjuvants. Because of the ability of QS-21 to improve the body’s immune response to very low doses of antigen, vaccine antigen may be ‘spared,’ which could significantly decrease the amount of antigen required for a given dose and make vaccine production more economical. | NA | NA | NA | NA | NA | Immunologic Factors | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12261 | Th1307 | CPG 10101 | NA | NA | NA | NA | NA | NA | NA | CPG 10101 is a synthetic oligodeoxynucleotide (ODN) in clinical trials. It is a toll-like receptor 9 (TLR9) agonist with antiviral and immunomodulatory properties that could potentially influence chronic infection with HCV. | Investigated for use/treatment in hepatitis (viral, C) and viral infection. | NA | NA | NA | NA | NA | NA | NA | Carbohydrates | NA | NA | NA | NA | Toll-like receptor 9 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12262 | Th1307 | CPG 10101 | NA | NA | NA | NA | NA | NA | NA | CPG 10101 is a synthetic oligodeoxynucleotide (ODN) in clinical trials. It is a toll-like receptor 9 (TLR9) agonist with antiviral and immunomodulatory properties that could potentially influence chronic infection with HCV. | Investigated for use/treatment in hepatitis (viral, C) and viral infection. | NA | NA | NA | NA | NA | NA | NA | Glycosides | NA | NA | NA | NA | Toll-like receptor 9 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12263 | Th1307 | CPG 10101 | NA | NA | NA | NA | NA | NA | NA | CPG 10101 is a synthetic oligodeoxynucleotide (ODN) in clinical trials. It is a toll-like receptor 9 (TLR9) agonist with antiviral and immunomodulatory properties that could potentially influence chronic infection with HCV. | Investigated for use/treatment in hepatitis (viral, C) and viral infection. | NA | NA | NA | NA | NA | NA | NA | Nucleic Acids, Nucleotides, and Nucleosides | NA | NA | NA | NA | Toll-like receptor 9 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12264 | Th1307 | CPG 10101 | NA | NA | NA | NA | NA | NA | NA | CPG 10101 is a synthetic oligodeoxynucleotide (ODN) in clinical trials. It is a toll-like receptor 9 (TLR9) agonist with antiviral and immunomodulatory properties that could potentially influence chronic infection with HCV. | Investigated for use/treatment in hepatitis (viral, C) and viral infection. | NA | NA | NA | NA | NA | NA | NA | Nucleotides | NA | NA | NA | NA | Toll-like receptor 9 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12265 | Th1307 | CPG 10101 | NA | NA | NA | NA | NA | NA | NA | CPG 10101 is a synthetic oligodeoxynucleotide (ODN) in clinical trials. It is a toll-like receptor 9 (TLR9) agonist with antiviral and immunomodulatory properties that could potentially influence chronic infection with HCV. | Investigated for use/treatment in hepatitis (viral, C) and viral infection. | NA | NA | NA | NA | NA | NA | NA | Oligonucleotides | NA | NA | NA | NA | Toll-like receptor 9 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12266 | Th1307 | CPG 10101 | NA | NA | NA | NA | NA | NA | NA | CPG 10101 is a synthetic oligodeoxynucleotide (ODN) in clinical trials. It is a toll-like receptor 9 (TLR9) agonist with antiviral and immunomodulatory properties that could potentially influence chronic infection with HCV. | Investigated for use/treatment in hepatitis (viral, C) and viral infection. | NA | NA | NA | NA | NA | NA | NA | Polynucleotides | NA | NA | NA | NA | Toll-like receptor 9 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12415 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12416 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Antigens | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12417 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Antigens, Surface | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12418 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Biological Factors | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12419 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Blood Proteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12420 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Carbohydrates | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12421 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Cell Adhesion Molecules | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12422 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Globulins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12423 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Glycoconjugates | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12424 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Glycoproteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12425 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | HIV Fusion Inhibitors | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12426 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Immunoglobulin Constant Regions | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12427 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Immunoglobulin Fc Fragments | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12428 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Immunoglobulin Fragments | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12429 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Immunoglobulins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12430 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Immunoproteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12431 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Membrane Glycoproteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12432 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Membrane Proteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12433 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Peptide Fragments | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12434 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Peptides | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12435 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Proteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12436 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Recombinant Fusion Proteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12437 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Recombinant Proteins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12438 | Th1321 | PRO-542 | NA | NA | NA | NA | NA | NA | NA | PRO 542 belongs to a new class of drugs, viral-entry inhibitor, which is intended to prevent HIV from entering and infecting cells. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. | Investigated for use/treatment in acquired immune deficiency syndrome (AIDS) and aids-related infections, HIV infection, and pediatric indications. | NA | PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells.Unlike currently approved therapies that block viral replication in cells already infected with HIV, PRO 542 is an antibody-like molecule that is designed to target and neutralize the virus in the bloodstream. Single doses of PRO 542 reduced concentrations of the human immunodeficiency (HIV) in the blood by 60% to 80% in a target population of highly treatment-experienced patients with PRO 542-sensitive virus. | NA | NA | NA | NA | NA | Serum Globulins | NA | NA | NA | NA | Free fatty acid receptor 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12668 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12669 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Antibodies | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12670 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Antibodies, Monoclonal | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12671 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Antibodies, Monoclonal, Humanized | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12672 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Antiinfectives for Systemic Use | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12673 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Blood Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12674 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Globulins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12675 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Immune Sera and Immunoglobulins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12676 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Immunoglobulins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12677 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Immunoproteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12678 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12679 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Serum Globulins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12680 | Th1344 | Motavizumab | >Th1344_Motavizumab QVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | 0 | Investigated for use/treatment in viral infection and pediatric indications. | NA | Motavizumab is a second generation, ultra-potent, affinity-matured, humanized mAb derived from palivizumab that reduces replication of Respiratory Syncytial Virus (RSV), a pathogen which causes lower respiratory tract disease. | NA | NA | NA | NA | NA | Specific Immunoglobulins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14612 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | Trogarzo | Theratechnologies Europe Limited | Theratechnologies Europe Limited | Intravenous | 200 mg | TROGARZO is contraindicated in patients with a prior hypersensitivity reaction to TROGARZO or any components of the product [see WARNINGS AND PRECAUTIONS]. | diarrhea, dizziness, nausea, and rash | Trogarzo is an antiviral medicine that prevents human immunodeficiency virus (HIV) from multiplying in your body. Trogarzo is used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). Ibalizumab-uiyk is not a cure for HIV or AIDS. Trogarzo is usually given after other treatments... | TROGARZO, in combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen. | NA | TROGARZO is a CD4-directed post-attachment HIV-1 inhibitor. | Link | Link | NA |
| 14613 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Anti-HIV Agents | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | Trogarzo | Theratechnologies Inc. | Theratechnologies Inc. | Intravenous | 150 mg/1mL | TROGARZO is contraindicated in patients with a prior hypersensitivity reaction to TROGARZO or any components of the product [see WARNINGS AND PRECAUTIONS]. | diarrhea, dizziness, nausea, and rash | Trogarzo is an antiviral medicine that prevents human immunodeficiency virus (HIV) from multiplying in your body. Trogarzo is used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). Ibalizumab-uiyk is not a cure for HIV or AIDS. Trogarzo is usually given after other treatments... | TROGARZO, in combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen. | NA | TROGARZO is a CD4-directed post-attachment HIV-1 inhibitor. | Link | Link | NA |
| 14614 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Anti-Infective Agents | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14615 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Anti-Retroviral Agents | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14616 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Antibodies | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14617 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Antibodies, Monoclonal | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14618 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Antibodies, Monoclonal, Humanized | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14619 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Antiinfectives for Systemic Use | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14620 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Antiviral Agents | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14621 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Antivirals for Systemic Use | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14622 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Blood Proteins | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14623 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | CD4-directed Antibody Interactions | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14624 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | CD4-directed Blocking Antibody | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14625 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Direct Acting Antivirals | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14626 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Globulins | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14627 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | HIV 1 Post-attachment Fusion Inhibitors | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14628 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | HIV Fusion Inhibitors | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14629 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Human Immunodeficiency Virus 1 Post-attachment Fusion Inhibitor | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14630 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Immunoglobulins | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14631 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Immunoproteins | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14632 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Proteins | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 14633 | Th1522 | Ibalizumab | >Th1522_Ibalizumab QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | NA | NA | NA | NA | NA | The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV [L1555]. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) [FDA label]. | Ibalizumab (also known as _ibalizumab-uiyk_ and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies [L1558, L1554]. This drug was approved in March 2018 for the management of treatment-resistant HIV [L1554]. | Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen [FDA label]. The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with =10 antiretroviral medications [L1554]. | Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo [L1554]. Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail [L1554]. | Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 [FDA label]. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion [L1555]. CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function [A32076]. In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action [L1559]. | Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment [FDA label]. | Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism [L1560]. | NA | 4.8 L [FDA label] | Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg [FDA label]. | Serum Globulins | NA | NA | NA | NA | T-cell surface glycoprotein CD4,C-C chemokine receptor type 5,C-X-C chemokine receptor type 4 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15037 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Clostridium difficile Toxin B | Zinplava | Merck Sharp & Dohme Corp. | Merck Sharp & Dohme Corp. | Intravenous | 25 mg/1mL | None. | nausea, fever, and headache. | Zinplava is a monoclonal antibody. Monoclonal antibodies are made to target only certain cells in the body. Bezlotoxumab works by binding to a specific toxin produced by the Clostridium difficile bacteria, to help neutralize the toxin's effects. Zinplava is used together with antibiotic medicine in adults... | Zinplava is a prescription medicine used to treat the symptoms of Clostridium difficile infection (CDI). Zinplava may be used alone or with other medications. | NA | Bezlotoxumab is a human monoclonal antibody that binds to C. difficile toxin B and neutralizes its effects. Bezlotoxumab is an IgG1 immunoglobulin with an approximate molecular weight of 148.2 kDa. | Link | Link | NA |
| 15038 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Antibodies | NA | NA | NA | NA | Clostridium difficile Toxin B | Zinplava | Merck Sharp & Dohme B.V. | Merck Sharp & Dohme B.V. | Intravenous | 25 mg/ml | None. | nausea, fever, and headache. | Zinplava is a monoclonal antibody. Monoclonal antibodies are made to target only certain cells in the body. Bezlotoxumab works by binding to a specific toxin produced by the Clostridium difficile bacteria, to help neutralize the toxin's effects. Zinplava is used together with antibiotic medicine in adults... | Zinplava is a prescription medicine used to treat the symptoms of Clostridium difficile infection (CDI). Zinplava may be used alone or with other medications. | NA | Bezlotoxumab is a human monoclonal antibody that binds to C. difficile toxin B and neutralizes its effects. Bezlotoxumab is an IgG1 immunoglobulin with an approximate molecular weight of 148.2 kDa. | Link | Link | NA |
| 15039 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Antibodies, Monoclonal | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15040 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Antiinfectives for Systemic Use | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15041 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Blood Proteins | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15042 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Globulins | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15043 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Immune Sera and Immunoglobulins | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15044 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Immunoglobulins | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15045 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Immunoproteins | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15046 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Proteins | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15047 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Serum Globulins | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15048 | Th1564 | Bezlotoxumab | >Th1564_Bezlotoxumab EVQLVQSGAEVKKSGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIFYPGDSSTRYSPSFQGQVTISADKSVNTAYLQWSSLKASDTAMYYCARRRNWGNAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | 19 Days | Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence. | Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence. | Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells. | A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. | No data available on overdosage. | Catabolism | Not absorbed since give IV | 7.33L | 0.317 L/day | Specific Immunoglobulins | NA | NA | NA | NA | Clostridium difficile Toxin B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15359 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Carcinoembryonic antigen | Scintimun | Cis Bio International | Cis Bio International | Intravenous | 1 mg | NA | The most common side effect with Scintimun (seen in more than 1 patient in 10) is the production of anti-mouse antibodies. | Scintimun is a kit for the preparation of a radioactive solution for injection. It contains the active substance besilesomab. | It is used to locate areas of infection or inflammation in adults with suspected osteomyelitis (bone infection) in the limbs, in combination with other appropriate imaging methods. | NA | NA | Link | Link | NA |
| 15360 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Antibodies | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15361 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Antibodies, Monoclonal | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15362 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Blood Proteins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15363 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Globulins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15364 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Immunoglobulins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15365 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Immunoproteins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15366 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Proteins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15367 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Radiopharmaceuticals | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15368 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Serum Globulins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15576 | Th1609 | Elapegademase | >Th1609_Elapegademase AQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPEFLAKFDYYMPAIAGSREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQAEGDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAIDLAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGYHTLEDTTLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIFKSTLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPA | 115000 | C1797H2795N477O544S12 | NA | NA | NA | This pharmacokinetic property has not been fully studied. | Elapegademase is a PEGylated recombinant adenosine deaminase. It can be defined molecularly as a genetically modified bovine adenosine deaminase with a modification in cysteine 74 for serine and with about 13 methoxy polyethylene glycol chains bound via carbonyl group in alanine and lysine residues.[F1937] Elapegademase is generated in _E. coli_, developed by Leadiant Biosciences and FDA approved on October 5, 2018.[L4654,F1939] | Elapegademase is approved for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.[L4654] This condition was previously treated by the use of bovine pegamedase as part of an enzyme replacement therapy.[L4655] ADA-SCID is a genetically inherited disorder that is very rare and characterized by a deficiency in the adenosine deaminase enzyme. The patients suffering from this disease often present with a compromised immune system. This condition is characterized by very low levels of white blood cells and immunoglobulin levels which results in severe and recurring infections.[L4656] | In clinical trials, elapegademase was shown to increase adenosine deaminase activity while reducing the concentrations of toxic metabolites which are the hallmark of ADA-SCID. As well, it was shown to improve the total lymphocyte count.[F1940] | The ADA-SCID is caused by the presence of mutations in the ADA gene which is responsible for the synthesis of adenosine deaminase. This enzyme is found throughout the body but it is mainly active in lymphocytes. The normal function of adenosine deaminase is to eliminate deoxyadenosine, created when DNA is degraded, by converting it into deoxyinosine. This degradation process is very important as deoxyadenosine is cytotoxic, especially for lymphocytes. Immature lymphocytes are particularly vulnerable as deoxyadenosine kills them before maturation making them unable to produce their immune function.[L4656] Therefore, based on the causes of ADA-SCID, elapegademase works by supplementing the levels of adenosine deaminase. Being a recombinant and an _E. coli_-produced molecule, the use of this drug eliminates the need to source the enzyme from animals, as it was previously.[L4654] | As elapegademase is a therapeutic protein, there is a potential risk of immunogenicity. There are no studies related to overdose but the highest weekly prescribed dose in clinical trials was 0.4 mg/kg. In nonclinical studies, a dosage of 1.8 fold of the clinical dose produced a slight increase in the activated partial thromboplastin time.[FDA label] | Metabolism studies have not been performed but it is thought to be degraded by proteases to small peptides and individual amino acids. | Elapegademase is administered intramuscularly and the reported Tmax, Cmax and AUC are approximately 60 hours, 240 mmol.h/L and 33000 hr.mmol/L as reported during a week.[FDA label] | This pharmacokinetic property has not been fully studied. | This pharmacokinetic property has not been fully studied. | Adjuvants, Immunologic | NA | NA | NA | NA | Adenosine | Revcovi | Leadiant Biosciences, Inc. | Leadiant Biosciences, Inc. | Intramuscular | 1.6 mg/1mL | None. | cough and vomiting | Revcovi is a man-made form of an enzyme called adenosine deaminase (ADA). ADA is important in the body for preventing the buildup of certain proteins harmful to the white blood cells that help your body fight infections. Revcovi is used to replace ADA in adults and children with adenosine deaminase severe... | Revcovi (elapegademase-lvlr) is a recombinant adenosine deaminase indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients. | (2S)-2-amino-6-(2-methoxyethoxycarbonylamino)hexanoic acid | NA | Link | Link | NA |
| 15577 | Th1609 | Elapegademase | >Th1609_Elapegademase AQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPEFLAKFDYYMPAIAGSREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQAEGDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAIDLAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGYHTLEDTTLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIFKSTLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPA | 115000 | C1797H2795N477O544S12 | NA | NA | NA | This pharmacokinetic property has not been fully studied. | Elapegademase is a PEGylated recombinant adenosine deaminase. It can be defined molecularly as a genetically modified bovine adenosine deaminase with a modification in cysteine 74 for serine and with about 13 methoxy polyethylene glycol chains bound via carbonyl group in alanine and lysine residues.[F1937] Elapegademase is generated in _E. coli_, developed by Leadiant Biosciences and FDA approved on October 5, 2018.[L4654,F1939] | Elapegademase is approved for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.[L4654] This condition was previously treated by the use of bovine pegamedase as part of an enzyme replacement therapy.[L4655] ADA-SCID is a genetically inherited disorder that is very rare and characterized by a deficiency in the adenosine deaminase enzyme. The patients suffering from this disease often present with a compromised immune system. This condition is characterized by very low levels of white blood cells and immunoglobulin levels which results in severe and recurring infections.[L4656] | In clinical trials, elapegademase was shown to increase adenosine deaminase activity while reducing the concentrations of toxic metabolites which are the hallmark of ADA-SCID. As well, it was shown to improve the total lymphocyte count.[F1940] | The ADA-SCID is caused by the presence of mutations in the ADA gene which is responsible for the synthesis of adenosine deaminase. This enzyme is found throughout the body but it is mainly active in lymphocytes. The normal function of adenosine deaminase is to eliminate deoxyadenosine, created when DNA is degraded, by converting it into deoxyinosine. This degradation process is very important as deoxyadenosine is cytotoxic, especially for lymphocytes. Immature lymphocytes are particularly vulnerable as deoxyadenosine kills them before maturation making them unable to produce their immune function.[L4656] Therefore, based on the causes of ADA-SCID, elapegademase works by supplementing the levels of adenosine deaminase. Being a recombinant and an _E. coli_-produced molecule, the use of this drug eliminates the need to source the enzyme from animals, as it was previously.[L4654] | As elapegademase is a therapeutic protein, there is a potential risk of immunogenicity. There are no studies related to overdose but the highest weekly prescribed dose in clinical trials was 0.4 mg/kg. In nonclinical studies, a dosage of 1.8 fold of the clinical dose produced a slight increase in the activated partial thromboplastin time.[FDA label] | Metabolism studies have not been performed but it is thought to be degraded by proteases to small peptides and individual amino acids. | Elapegademase is administered intramuscularly and the reported Tmax, Cmax and AUC are approximately 60 hours, 240 mmol.h/L and 33000 hr.mmol/L as reported during a week.[FDA label] | This pharmacokinetic property has not been fully studied. | This pharmacokinetic property has not been fully studied. | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Adenosine | Revcovi | Chiesi USA, Inc. | Chiesi USA, Inc. | Intramuscular | 1.6 mg/1mL | None. | cough and vomiting | Revcovi is a man-made form of an enzyme called adenosine deaminase (ADA). ADA is important in the body for preventing the buildup of certain proteins harmful to the white blood cells that help your body fight infections. Revcovi is used to replace ADA in adults and children with adenosine deaminase severe... | Revcovi (elapegademase-lvlr) is a recombinant adenosine deaminase indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients. | (2S)-2-amino-6-(2-methoxyethoxycarbonylamino)hexanoic acid | NA | Link | Link | NA |
| 15578 | Th1609 | Elapegademase | >Th1609_Elapegademase AQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPEFLAKFDYYMPAIAGSREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQAEGDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAIDLAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGYHTLEDTTLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIFKSTLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPA | 115000 | C1797H2795N477O544S12 | NA | NA | NA | This pharmacokinetic property has not been fully studied. | Elapegademase is a PEGylated recombinant adenosine deaminase. It can be defined molecularly as a genetically modified bovine adenosine deaminase with a modification in cysteine 74 for serine and with about 13 methoxy polyethylene glycol chains bound via carbonyl group in alanine and lysine residues.[F1937] Elapegademase is generated in _E. coli_, developed by Leadiant Biosciences and FDA approved on October 5, 2018.[L4654,F1939] | Elapegademase is approved for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.[L4654] This condition was previously treated by the use of bovine pegamedase as part of an enzyme replacement therapy.[L4655] ADA-SCID is a genetically inherited disorder that is very rare and characterized by a deficiency in the adenosine deaminase enzyme. The patients suffering from this disease often present with a compromised immune system. This condition is characterized by very low levels of white blood cells and immunoglobulin levels which results in severe and recurring infections.[L4656] | In clinical trials, elapegademase was shown to increase adenosine deaminase activity while reducing the concentrations of toxic metabolites which are the hallmark of ADA-SCID. As well, it was shown to improve the total lymphocyte count.[F1940] | The ADA-SCID is caused by the presence of mutations in the ADA gene which is responsible for the synthesis of adenosine deaminase. This enzyme is found throughout the body but it is mainly active in lymphocytes. The normal function of adenosine deaminase is to eliminate deoxyadenosine, created when DNA is degraded, by converting it into deoxyinosine. This degradation process is very important as deoxyadenosine is cytotoxic, especially for lymphocytes. Immature lymphocytes are particularly vulnerable as deoxyadenosine kills them before maturation making them unable to produce their immune function.[L4656] Therefore, based on the causes of ADA-SCID, elapegademase works by supplementing the levels of adenosine deaminase. Being a recombinant and an _E. coli_-produced molecule, the use of this drug eliminates the need to source the enzyme from animals, as it was previously.[L4654] | As elapegademase is a therapeutic protein, there is a potential risk of immunogenicity. There are no studies related to overdose but the highest weekly prescribed dose in clinical trials was 0.4 mg/kg. In nonclinical studies, a dosage of 1.8 fold of the clinical dose produced a slight increase in the activated partial thromboplastin time.[FDA label] | Metabolism studies have not been performed but it is thought to be degraded by proteases to small peptides and individual amino acids. | Elapegademase is administered intramuscularly and the reported Tmax, Cmax and AUC are approximately 60 hours, 240 mmol.h/L and 33000 hr.mmol/L as reported during a week.[FDA label] | This pharmacokinetic property has not been fully studied. | This pharmacokinetic property has not been fully studied. | Antineoplastic and Immunomodulating Agents | NA | NA | NA | NA | Adenosine | NA | NA | NA | NA | NA | NA | NA | NA | NA | (2S)-2-amino-6-(2-methoxyethoxycarbonylamino)hexanoic acid | NA | Link | NA | NA |
| 15579 | Th1609 | Elapegademase | >Th1609_Elapegademase AQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPEFLAKFDYYMPAIAGSREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQAEGDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAIDLAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGYHTLEDTTLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIFKSTLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPA | 115000 | C1797H2795N477O544S12 | NA | NA | NA | This pharmacokinetic property has not been fully studied. | Elapegademase is a PEGylated recombinant adenosine deaminase. It can be defined molecularly as a genetically modified bovine adenosine deaminase with a modification in cysteine 74 for serine and with about 13 methoxy polyethylene glycol chains bound via carbonyl group in alanine and lysine residues.[F1937] Elapegademase is generated in _E. coli_, developed by Leadiant Biosciences and FDA approved on October 5, 2018.[L4654,F1939] | Elapegademase is approved for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.[L4654] This condition was previously treated by the use of bovine pegamedase as part of an enzyme replacement therapy.[L4655] ADA-SCID is a genetically inherited disorder that is very rare and characterized by a deficiency in the adenosine deaminase enzyme. The patients suffering from this disease often present with a compromised immune system. This condition is characterized by very low levels of white blood cells and immunoglobulin levels which results in severe and recurring infections.[L4656] | In clinical trials, elapegademase was shown to increase adenosine deaminase activity while reducing the concentrations of toxic metabolites which are the hallmark of ADA-SCID. As well, it was shown to improve the total lymphocyte count.[F1940] | The ADA-SCID is caused by the presence of mutations in the ADA gene which is responsible for the synthesis of adenosine deaminase. This enzyme is found throughout the body but it is mainly active in lymphocytes. The normal function of adenosine deaminase is to eliminate deoxyadenosine, created when DNA is degraded, by converting it into deoxyinosine. This degradation process is very important as deoxyadenosine is cytotoxic, especially for lymphocytes. Immature lymphocytes are particularly vulnerable as deoxyadenosine kills them before maturation making them unable to produce their immune function.[L4656] Therefore, based on the causes of ADA-SCID, elapegademase works by supplementing the levels of adenosine deaminase. Being a recombinant and an _E. coli_-produced molecule, the use of this drug eliminates the need to source the enzyme from animals, as it was previously.[L4654] | As elapegademase is a therapeutic protein, there is a potential risk of immunogenicity. There are no studies related to overdose but the highest weekly prescribed dose in clinical trials was 0.4 mg/kg. In nonclinical studies, a dosage of 1.8 fold of the clinical dose produced a slight increase in the activated partial thromboplastin time.[FDA label] | Metabolism studies have not been performed but it is thought to be degraded by proteases to small peptides and individual amino acids. | Elapegademase is administered intramuscularly and the reported Tmax, Cmax and AUC are approximately 60 hours, 240 mmol.h/L and 33000 hr.mmol/L as reported during a week.[FDA label] | This pharmacokinetic property has not been fully studied. | This pharmacokinetic property has not been fully studied. | Enzyme Replacement Therapy | NA | NA | NA | NA | Adenosine | NA | NA | NA | NA | NA | NA | NA | NA | NA | (2S)-2-amino-6-(2-methoxyethoxycarbonylamino)hexanoic acid | NA | Link | NA | NA |
| 15580 | Th1609 | Elapegademase | >Th1609_Elapegademase AQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPEFLAKFDYYMPAIAGSREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQAEGDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAIDLAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGYHTLEDTTLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIFKSTLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPA | 115000 | C1797H2795N477O544S12 | NA | NA | NA | This pharmacokinetic property has not been fully studied. | Elapegademase is a PEGylated recombinant adenosine deaminase. It can be defined molecularly as a genetically modified bovine adenosine deaminase with a modification in cysteine 74 for serine and with about 13 methoxy polyethylene glycol chains bound via carbonyl group in alanine and lysine residues.[F1937] Elapegademase is generated in _E. coli_, developed by Leadiant Biosciences and FDA approved on October 5, 2018.[L4654,F1939] | Elapegademase is approved for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.[L4654] This condition was previously treated by the use of bovine pegamedase as part of an enzyme replacement therapy.[L4655] ADA-SCID is a genetically inherited disorder that is very rare and characterized by a deficiency in the adenosine deaminase enzyme. The patients suffering from this disease often present with a compromised immune system. This condition is characterized by very low levels of white blood cells and immunoglobulin levels which results in severe and recurring infections.[L4656] | In clinical trials, elapegademase was shown to increase adenosine deaminase activity while reducing the concentrations of toxic metabolites which are the hallmark of ADA-SCID. As well, it was shown to improve the total lymphocyte count.[F1940] | The ADA-SCID is caused by the presence of mutations in the ADA gene which is responsible for the synthesis of adenosine deaminase. This enzyme is found throughout the body but it is mainly active in lymphocytes. The normal function of adenosine deaminase is to eliminate deoxyadenosine, created when DNA is degraded, by converting it into deoxyinosine. This degradation process is very important as deoxyadenosine is cytotoxic, especially for lymphocytes. Immature lymphocytes are particularly vulnerable as deoxyadenosine kills them before maturation making them unable to produce their immune function.[L4656] Therefore, based on the causes of ADA-SCID, elapegademase works by supplementing the levels of adenosine deaminase. Being a recombinant and an _E. coli_-produced molecule, the use of this drug eliminates the need to source the enzyme from animals, as it was previously.[L4654] | As elapegademase is a therapeutic protein, there is a potential risk of immunogenicity. There are no studies related to overdose but the highest weekly prescribed dose in clinical trials was 0.4 mg/kg. In nonclinical studies, a dosage of 1.8 fold of the clinical dose produced a slight increase in the activated partial thromboplastin time.[FDA label] | Metabolism studies have not been performed but it is thought to be degraded by proteases to small peptides and individual amino acids. | Elapegademase is administered intramuscularly and the reported Tmax, Cmax and AUC are approximately 60 hours, 240 mmol.h/L and 33000 hr.mmol/L as reported during a week.[FDA label] | This pharmacokinetic property has not been fully studied. | This pharmacokinetic property has not been fully studied. | Pegylated agents | NA | NA | NA | NA | Adenosine | NA | NA | NA | NA | NA | NA | NA | NA | NA | (2S)-2-amino-6-(2-methoxyethoxycarbonylamino)hexanoic acid | NA | Link | NA | NA |
| 15581 | Th1609 | Elapegademase | >Th1609_Elapegademase AQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPEFLAKFDYYMPAIAGSREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQAEGDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAIDLAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGYHTLEDTTLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIFKSTLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPA | 115000 | C1797H2795N477O544S12 | NA | NA | NA | This pharmacokinetic property has not been fully studied. | Elapegademase is a PEGylated recombinant adenosine deaminase. It can be defined molecularly as a genetically modified bovine adenosine deaminase with a modification in cysteine 74 for serine and with about 13 methoxy polyethylene glycol chains bound via carbonyl group in alanine and lysine residues.[F1937] Elapegademase is generated in _E. coli_, developed by Leadiant Biosciences and FDA approved on October 5, 2018.[L4654,F1939] | Elapegademase is approved for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.[L4654] This condition was previously treated by the use of bovine pegamedase as part of an enzyme replacement therapy.[L4655] ADA-SCID is a genetically inherited disorder that is very rare and characterized by a deficiency in the adenosine deaminase enzyme. The patients suffering from this disease often present with a compromised immune system. This condition is characterized by very low levels of white blood cells and immunoglobulin levels which results in severe and recurring infections.[L4656] | In clinical trials, elapegademase was shown to increase adenosine deaminase activity while reducing the concentrations of toxic metabolites which are the hallmark of ADA-SCID. As well, it was shown to improve the total lymphocyte count.[F1940] | The ADA-SCID is caused by the presence of mutations in the ADA gene which is responsible for the synthesis of adenosine deaminase. This enzyme is found throughout the body but it is mainly active in lymphocytes. The normal function of adenosine deaminase is to eliminate deoxyadenosine, created when DNA is degraded, by converting it into deoxyinosine. This degradation process is very important as deoxyadenosine is cytotoxic, especially for lymphocytes. Immature lymphocytes are particularly vulnerable as deoxyadenosine kills them before maturation making them unable to produce their immune function.[L4656] Therefore, based on the causes of ADA-SCID, elapegademase works by supplementing the levels of adenosine deaminase. Being a recombinant and an _E. coli_-produced molecule, the use of this drug eliminates the need to source the enzyme from animals, as it was previously.[L4654] | As elapegademase is a therapeutic protein, there is a potential risk of immunogenicity. There are no studies related to overdose but the highest weekly prescribed dose in clinical trials was 0.4 mg/kg. In nonclinical studies, a dosage of 1.8 fold of the clinical dose produced a slight increase in the activated partial thromboplastin time.[FDA label] | Metabolism studies have not been performed but it is thought to be degraded by proteases to small peptides and individual amino acids. | Elapegademase is administered intramuscularly and the reported Tmax, Cmax and AUC are approximately 60 hours, 240 mmol.h/L and 33000 hr.mmol/L as reported during a week.[FDA label] | This pharmacokinetic property has not been fully studied. | This pharmacokinetic property has not been fully studied. | Proteins | NA | NA | NA | NA | Adenosine | NA | NA | NA | NA | NA | NA | NA | NA | NA | (2S)-2-amino-6-(2-methoxyethoxycarbonylamino)hexanoic acid | NA | Link | NA | NA |
| 15582 | Th1609 | Elapegademase | >Th1609_Elapegademase AQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPEFLAKFDYYMPAIAGSREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQAEGDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAIDLAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGYHTLEDTTLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIFKSTLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPA | 115000 | C1797H2795N477O544S12 | NA | NA | NA | This pharmacokinetic property has not been fully studied. | Elapegademase is a PEGylated recombinant adenosine deaminase. It can be defined molecularly as a genetically modified bovine adenosine deaminase with a modification in cysteine 74 for serine and with about 13 methoxy polyethylene glycol chains bound via carbonyl group in alanine and lysine residues.[F1937] Elapegademase is generated in _E. coli_, developed by Leadiant Biosciences and FDA approved on October 5, 2018.[L4654,F1939] | Elapegademase is approved for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.[L4654] This condition was previously treated by the use of bovine pegamedase as part of an enzyme replacement therapy.[L4655] ADA-SCID is a genetically inherited disorder that is very rare and characterized by a deficiency in the adenosine deaminase enzyme. The patients suffering from this disease often present with a compromised immune system. This condition is characterized by very low levels of white blood cells and immunoglobulin levels which results in severe and recurring infections.[L4656] | In clinical trials, elapegademase was shown to increase adenosine deaminase activity while reducing the concentrations of toxic metabolites which are the hallmark of ADA-SCID. As well, it was shown to improve the total lymphocyte count.[F1940] | The ADA-SCID is caused by the presence of mutations in the ADA gene which is responsible for the synthesis of adenosine deaminase. This enzyme is found throughout the body but it is mainly active in lymphocytes. The normal function of adenosine deaminase is to eliminate deoxyadenosine, created when DNA is degraded, by converting it into deoxyinosine. This degradation process is very important as deoxyadenosine is cytotoxic, especially for lymphocytes. Immature lymphocytes are particularly vulnerable as deoxyadenosine kills them before maturation making them unable to produce their immune function.[L4656] Therefore, based on the causes of ADA-SCID, elapegademase works by supplementing the levels of adenosine deaminase. Being a recombinant and an _E. coli_-produced molecule, the use of this drug eliminates the need to source the enzyme from animals, as it was previously.[L4654] | As elapegademase is a therapeutic protein, there is a potential risk of immunogenicity. There are no studies related to overdose but the highest weekly prescribed dose in clinical trials was 0.4 mg/kg. In nonclinical studies, a dosage of 1.8 fold of the clinical dose produced a slight increase in the activated partial thromboplastin time.[FDA label] | Metabolism studies have not been performed but it is thought to be degraded by proteases to small peptides and individual amino acids. | Elapegademase is administered intramuscularly and the reported Tmax, Cmax and AUC are approximately 60 hours, 240 mmol.h/L and 33000 hr.mmol/L as reported during a week.[FDA label] | This pharmacokinetic property has not been fully studied. | This pharmacokinetic property has not been fully studied. | Recombinant Proteins | NA | NA | NA | NA | Adenosine | NA | NA | NA | NA | NA | NA | NA | NA | NA | (2S)-2-amino-6-(2-methoxyethoxycarbonylamino)hexanoic acid | NA | Link | NA | NA |
| 15948 | Th1655 | Atoltivimab | >Th1655_Atoltivimab QVQLVESGGGVVQPGRSLRLSCAASGFTFNNYGMHWVRQAPGMGLEWVAVIWHDGSDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWNLFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 145097.54 | C6448H9954N1726O2002S44 | NA | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Atoltivimab is indicated in combination with [Odesivimab] and [Maftivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Atoltivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Atoltivimab is a fully-humanized IgG1 | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-8 of 17,100 ± 4480 mg | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.[L17320] | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.[L17320] | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Envelope glycoprotein | Inmazeb | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | None. | fever, chills, fast heart rate, fast, shallow breathing, vomiting, low blood pressure (hypotension), diarrhea, and low blood oxygen (hypoxia) | Atoltivimab, maftivimab, and odesivimab-ebgn combination injection is used to treat infection cause by Zaire ebolavirus. This medicine is to be given only by or under the direct supervision of your doctor. Before using Inmazeb In deciding to use a medicine, the risks of taking the medicine must be weighed... | Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn) is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies used to treat infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. | NA | NA | Link | Link | NA |
| 15949 | Th1655 | Atoltivimab | >Th1655_Atoltivimab QVQLVESGGGVVQPGRSLRLSCAASGFTFNNYGMHWVRQAPGMGLEWVAVIWHDGSDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWNLFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 145097.54 | C6448H9954N1726O2002S44 | NA | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Atoltivimab is indicated in combination with [Odesivimab] and [Maftivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Atoltivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Atoltivimab is a fully-humanized IgG1 | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-8 of 17,100 ± 4480 mg | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.[L17320] | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.[L17320] | Antibodies, Monoclonal | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15950 | Th1655 | Atoltivimab | >Th1655_Atoltivimab QVQLVESGGGVVQPGRSLRLSCAASGFTFNNYGMHWVRQAPGMGLEWVAVIWHDGSDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWNLFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 145097.54 | C6448H9954N1726O2002S44 | NA | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Atoltivimab is indicated in combination with [Odesivimab] and [Maftivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Atoltivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Atoltivimab is a fully-humanized IgG1 | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-8 of 17,100 ± 4480 mg | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.[L17320] | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.[L17320] | Antibodies, Monoclonal, Humanized | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15951 | Th1655 | Atoltivimab | >Th1655_Atoltivimab QVQLVESGGGVVQPGRSLRLSCAASGFTFNNYGMHWVRQAPGMGLEWVAVIWHDGSDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWNLFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 145097.54 | C6448H9954N1726O2002S44 | NA | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Atoltivimab is indicated in combination with [Odesivimab] and [Maftivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Atoltivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Atoltivimab is a fully-humanized IgG1 | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-8 of 17,100 ± 4480 mg | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.[L17320] | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.[L17320] | Blood Proteins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15952 | Th1655 | Atoltivimab | >Th1655_Atoltivimab QVQLVESGGGVVQPGRSLRLSCAASGFTFNNYGMHWVRQAPGMGLEWVAVIWHDGSDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWNLFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 145097.54 | C6448H9954N1726O2002S44 | NA | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Atoltivimab is indicated in combination with [Odesivimab] and [Maftivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Atoltivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Atoltivimab is a fully-humanized IgG1 | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-8 of 17,100 ± 4480 mg | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.[L17320] | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.[L17320] | Immunoglobulins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15953 | Th1655 | Atoltivimab | >Th1655_Atoltivimab QVQLVESGGGVVQPGRSLRLSCAASGFTFNNYGMHWVRQAPGMGLEWVAVIWHDGSDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWNLFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 145097.54 | C6448H9954N1726O2002S44 | NA | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Atoltivimab is indicated in combination with [Odesivimab] and [Maftivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Atoltivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Atoltivimab is a fully-humanized IgG1 | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-8 of 17,100 ± 4480 mg | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.[L17320] | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.[L17320] | Proteins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15954 | Th1655 | Atoltivimab | >Th1655_Atoltivimab QVQLVESGGGVVQPGRSLRLSCAASGFTFNNYGMHWVRQAPGMGLEWVAVIWHDGSDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWNLFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 145097.54 | C6448H9954N1726O2002S44 | NA | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Atoltivimab is indicated in combination with [Odesivimab] and [Maftivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Atoltivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Atoltivimab is a fully-humanized IgG1 | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-8 of 17,100 ± 4480 mg | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.[L17320] | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.[L17320] | Serum Globulins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15955 | Th1655 | Atoltivimab | >Th1655_Atoltivimab QVQLVESGGGVVQPGRSLRLSCAASGFTFNNYGMHWVRQAPGMGLEWVAVIWHDGSDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWNLFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 145097.54 | C6448H9954N1726O2002S44 | NA | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Atoltivimab is indicated in combination with [Odesivimab] and [Maftivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Atoltivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Atoltivimab is a fully-humanized IgG1 | NA | NA | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-8 of 17,100 ± 4480 mg | Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.[L17320] | Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.[L17320] | Treatments for Ebola Virus Disease | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15956 | Th1656 | Maftivimab | >Th1656_Maftivimab EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143948.11 | C6368H9886N1706O2008S46 | NA | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Maftivimab is indicated in combination with [Odesivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Maftivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Maftivimab is a fully-humanized IgG1 | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Envelope glycoprotein | Inmazeb | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | None. | fever, chills, fast heart rate, fast, shallow breathing, vomiting, low blood pressure (hypotension), diarrhea, and low blood oxygen (hypoxia) | Atoltivimab, maftivimab, and odesivimab-ebgn combination injection is used to treat infection cause by Zaire ebolavirus. This medicine is to be given only by or under the direct supervision of your doctor. Before using Inmazeb In deciding to use a medicine, the risks of taking the medicine must be weighed... | Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn) is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies used to treat infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. | NA | NA | Link | Link | NA |
| 15957 | Th1656 | Maftivimab | >Th1656_Maftivimab EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143948.11 | C6368H9886N1706O2008S46 | NA | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Maftivimab is indicated in combination with [Odesivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Maftivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Maftivimab is a fully-humanized IgG1 | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] | Antibodies, Monoclonal | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15958 | Th1656 | Maftivimab | >Th1656_Maftivimab EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143948.11 | C6368H9886N1706O2008S46 | NA | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Maftivimab is indicated in combination with [Odesivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Maftivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Maftivimab is a fully-humanized IgG1 | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] | Antibodies, Monoclonal, Humanized | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15959 | Th1656 | Maftivimab | >Th1656_Maftivimab EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143948.11 | C6368H9886N1706O2008S46 | NA | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Maftivimab is indicated in combination with [Odesivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Maftivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Maftivimab is a fully-humanized IgG1 | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] | Blood Proteins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15960 | Th1656 | Maftivimab | >Th1656_Maftivimab EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143948.11 | C6368H9886N1706O2008S46 | NA | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Maftivimab is indicated in combination with [Odesivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Maftivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Maftivimab is a fully-humanized IgG1 | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] | Immunoglobulins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15961 | Th1656 | Maftivimab | >Th1656_Maftivimab EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143948.11 | C6368H9886N1706O2008S46 | NA | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Maftivimab is indicated in combination with [Odesivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Maftivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Maftivimab is a fully-humanized IgG1 | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] | Proteins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15962 | Th1656 | Maftivimab | >Th1656_Maftivimab EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143948.11 | C6368H9886N1706O2008S46 | NA | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Maftivimab is indicated in combination with [Odesivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Maftivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Maftivimab is a fully-humanized IgG1 | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] | Serum Globulins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15963 | Th1656 | Maftivimab | >Th1656_Maftivimab EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143948.11 | C6368H9886N1706O2008S46 | NA | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Maftivimab is indicated in combination with [Odesivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Maftivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Maftivimab is a fully-humanized IgG1 | NA | NA | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] | Treatments for Ebola Virus Disease | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15964 | Th1657 | Odesivimab | >Th1657_Odesivimab EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARTWFGELYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 146164.54 | C6506H10024N1720O2030S42 | NA | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Odesivimab is indicated in combination with [Maftivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Odesivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Odesivimab is a fully-humanized IgG1 | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1260 ± 81.2 mg/L and a mean AUC0-8 of 25,600 ± 5040 mg | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.[L17320] | Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.[L17320] | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Envelope glycoprotein | Inmazeb | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | None. | fever, chills, fast heart rate, fast, shallow breathing, vomiting, low blood pressure (hypotension), diarrhea, and low blood oxygen (hypoxia) | Atoltivimab, maftivimab, and odesivimab-ebgn combination injection is used to treat infection cause by Zaire ebolavirus. This medicine is to be given only by or under the direct supervision of your doctor. Before using Inmazeb In deciding to use a medicine, the risks of taking the medicine must be weighed... | Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn) is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies used to treat infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. | NA | NA | Link | Link | NA |
| 15965 | Th1657 | Odesivimab | >Th1657_Odesivimab EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARTWFGELYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 146164.54 | C6506H10024N1720O2030S42 | NA | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Odesivimab is indicated in combination with [Maftivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Odesivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Odesivimab is a fully-humanized IgG1 | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1260 ± 81.2 mg/L and a mean AUC0-8 of 25,600 ± 5040 mg | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.[L17320] | Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.[L17320] | Antibodies, Monoclonal | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15966 | Th1657 | Odesivimab | >Th1657_Odesivimab EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARTWFGELYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 146164.54 | C6506H10024N1720O2030S42 | NA | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Odesivimab is indicated in combination with [Maftivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Odesivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Odesivimab is a fully-humanized IgG1 | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1260 ± 81.2 mg/L and a mean AUC0-8 of 25,600 ± 5040 mg | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.[L17320] | Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.[L17320] | Antibodies, Monoclonal, Humanized | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15967 | Th1657 | Odesivimab | >Th1657_Odesivimab EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARTWFGELYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 146164.54 | C6506H10024N1720O2030S42 | NA | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Odesivimab is indicated in combination with [Maftivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Odesivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Odesivimab is a fully-humanized IgG1 | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1260 ± 81.2 mg/L and a mean AUC0-8 of 25,600 ± 5040 mg | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.[L17320] | Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.[L17320] | Blood Proteins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15968 | Th1657 | Odesivimab | >Th1657_Odesivimab EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARTWFGELYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 146164.54 | C6506H10024N1720O2030S42 | NA | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Odesivimab is indicated in combination with [Maftivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Odesivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Odesivimab is a fully-humanized IgG1 | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1260 ± 81.2 mg/L and a mean AUC0-8 of 25,600 ± 5040 mg | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.[L17320] | Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.[L17320] | Immunoglobulins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15969 | Th1657 | Odesivimab | >Th1657_Odesivimab EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARTWFGELYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 146164.54 | C6506H10024N1720O2030S42 | NA | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Odesivimab is indicated in combination with [Maftivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Odesivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Odesivimab is a fully-humanized IgG1 | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1260 ± 81.2 mg/L and a mean AUC0-8 of 25,600 ± 5040 mg | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.[L17320] | Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.[L17320] | Proteins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15970 | Th1657 | Odesivimab | >Th1657_Odesivimab EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARTWFGELYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 146164.54 | C6506H10024N1720O2030S42 | NA | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Odesivimab is indicated in combination with [Maftivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Odesivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Odesivimab is a fully-humanized IgG1 | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1260 ± 81.2 mg/L and a mean AUC0-8 of 25,600 ± 5040 mg | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.[L17320] | Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.[L17320] | Serum Globulins | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15971 | Th1657 | Odesivimab | >Th1657_Odesivimab EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSAIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARTWFGELYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 146164.54 | C6506H10024N1720O2030S42 | NA | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.[L17320] | Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.[A221825] Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.[A222078] The chief surface target of EBOV particles is the GP1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.[A221825, A221830] A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 | Odesivimab is indicated in combination with [Maftivimab] and [Atoltivimab] for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored.[L17320] | Odesivimab is a fully-humanized IgG1 | Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%.[A221825] EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.[A221825, A221830] Odesivimab is a fully-humanized IgG1 | NA | NA | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1260 ± 81.2 mg/L and a mean AUC0-8 of 25,600 ± 5040 mg | Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.[L17320] | Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.[L17320] | Treatments for Ebola Virus Disease | NA | NA | NA | NA | Envelope glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15972 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Spike glycoprotein | Casirivimab and Imdevimab | Hoffmann La Roche | Hoffmann La Roche | Intravenous | NA | NA | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, severe dizziness, rash, and itching | Regen-Cov is a prescription medicine used to treat the symptoms of COVID-19 (EUA). Regen-Cov may be used alone or with other medications. | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, severe dizziness, rash, and itching | NA | NA | Link | Link | NA |
| 15973 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Antibodies | NA | NA | NA | NA | Spike glycoprotein | Casirivimab With Imdevimab | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | NA | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, severe dizziness, rash, and itching | Regen-Cov is a prescription medicine used to treat the symptoms of COVID-19 (EUA). Regen-Cov may be used alone or with other medications. | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, severe dizziness, rash, and itching | NA | NA | Link | Link | NA |
| 15974 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Antibodies, Monoclonal | NA | NA | NA | NA | Spike glycoprotein | Imdevimab | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | 300 mg/2.5mL | NA | use in treating conditions caused by coronavirus. | Imdevimab is an experimental medicine being studied for use in treating conditions caused by coronavirus. It is not yet known if imdevimab is a safe and effective treatment for any condition. | throat irritation, swelling in your face or throat; dizziness, a light-headed feeling (like you might pass out); chest pain, wheezing, shortness of breath; fever, chills, sweating, nausea, flushing (sudden warmth, redness, or tingly feeling); fast or slow heartbeats, headache, pounding in your neck or ears; weakness, tiredness; rash, itching; or muscle pain. | NA | NA | Link | Link | NA |
| 15975 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Approved Treatments for COVID-19 | NA | NA | NA | NA | Spike glycoprotein | Imdevimab | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | 1332 mg/11.1mL | NA | use in treating conditions caused by coronavirus. | Imdevimab is an experimental medicine being studied for use in treating conditions caused by coronavirus. It is not yet known if imdevimab is a safe and effective treatment for any condition. | throat irritation, swelling in your face or throat; dizziness, a light-headed feeling (like you might pass out); chest pain, wheezing, shortness of breath; fever, chills, sweating, nausea, flushing (sudden warmth, redness, or tingly feeling); fast or slow heartbeats, headache, pounding in your neck or ears; weakness, tiredness; rash, itching; or muscle pain. | NA | NA | Link | Link | NA |
| 15976 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Blood Proteins | NA | NA | NA | NA | Spike glycoprotein | Regen-cov | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | None. | infusion-related reactions (hives, itching, flushing, fever, shortness of breath, chest tightness, nausea, vomiting, rash) and severe allergic reactions (anaphylaxis). | NA | Regen-Cov is a prescription medicine used to treat the symptoms of COVID-19 (EUA). Regen-Cov may be used alone or with other medications. | NA | Casirivimab, a human immunoglobulin G-1 (IgG1) monoclonal antibody (mAb), is a covalent heterotetramer consisting of 2 heavy chains and 2 light chains produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture and has an approximate molecular weight of 145.23 kDa. | Link | Link | NA |
| 15977 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Immunoglobulins | NA | NA | NA | NA | Spike glycoprotein | Regen-cov | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | None. | infusion-related reactions (hives, itching, flushing, fever, shortness of breath, chest tightness, nausea, vomiting, rash) and severe allergic reactions (anaphylaxis). | NA | Regen-Cov is a prescription medicine used to treat the symptoms of COVID-19 (EUA). Regen-Cov may be used alone or with other medications. | NA | Casirivimab, a human immunoglobulin G-1 (IgG1) monoclonal antibody (mAb), is a covalent heterotetramer consisting of 2 heavy chains and 2 light chains produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture and has an approximate molecular weight of 145.23 kDa. | Link | Link | NA |
| 15978 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Immunoproteins | NA | NA | NA | NA | Spike glycoprotein | Ronapreve | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | NA | NA | The most common side effects with Ronapreve (which may affect up to 1 in 10 people) are allergic reactions, which include infusion related reactions and injection site reactions. | Ronapreve was found to be effective at preventing people from getting infected and developing symptoms after contact: amongst people who tested negative for SARS-CoV-2 following contact, fewer people given Ronapreve developed symptoms within 29 days of their test results compared with people given placebo (1.5% (11 out of 753) for Ronapreve compared with 7.8% (59 out of 752 people) for placebo). | Ronapreve is a medicine used for treating COVID-19 in adults and adolescents (from 12 years of age and weighing at least 40 kilograms) who do not require supplemental oxygen and who are at increased risk of their disease becoming severe. | NA | NA | Link | Link | NA |
| 15979 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Proteins | NA | NA | NA | NA | Spike glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15980 | Th1658 | Imdevimab | >Th1658_Imdevimab QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYAMYWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYCASGSDYGDYLLVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Imdevimab is a monoclonal antibody combined with [casirivimab] in Regeneron's antibody cocktail known as REGEN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21, 2020, the FDA authorized emergency approval of REGN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data on imdevimab are not yet available, and further evaluation of this investigational therapy will continue.[L23529,L23539,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23534,L23539] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Imdevimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the target cell by binding to the ACE2 receptor.[A224424,A224434,L23529] Together with casirivimab, imdevimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for imdevimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Serum Globulins | NA | NA | NA | NA | Spike glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15981 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Spike glycoprotein | Casirivimab | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | 300 mg/2.5mL | NA | pain, bleeding, bruising of the skin, soreness, swelling, or infection at injection site | On January 24, 2022, FDA reissued the emergency use authorization (EUA) for casirivimab and imdevimab stating that the combination regimen is not authorized for treatment of mild to moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency. Given the prevalence of the Omicron variant in the United States, casirivimab and imdevimab is not recommended for use anywhere for mild to moderate disease at the present time. | to treat mild to moderate symptoms of COVID-19. to prevent COVID-19 in those who are not fully vaccinated against COVID-19 or who are vaccinated, but have a weakened immune system, or are taking a medication that affects the immune system and who have had close contact or are at high risk of close contact to someone who is infected with the SARS-CoV-2 virus (for example, nursing homes, prisons). | NA | NA | Link | Link | NA |
| 15982 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Antibodies | NA | NA | NA | NA | Spike glycoprotein | Casirivimab | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | 1332 mg/11.1mL | NA | pain, bleeding, bruising of the skin, soreness, swelling, or infection at injection site | On January 24, 2022, FDA reissued the emergency use authorization (EUA) for casirivimab and imdevimab stating that the combination regimen is not authorized for treatment of mild to moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency. Given the prevalence of the Omicron variant in the United States, casirivimab and imdevimab is not recommended for use anywhere for mild to moderate disease at the present time. | to treat mild to moderate symptoms of COVID-19. to prevent COVID-19 in those who are not fully vaccinated against COVID-19 or who are vaccinated, but have a weakened immune system, or are taking a medication that affects the immune system and who have had close contact or are at high risk of close contact to someone who is infected with the SARS-CoV-2 virus (for example, nursing homes, prisons). | NA | NA | Link | Link | NA |
| 15983 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Antibodies, Monoclonal | NA | NA | NA | NA | Spike glycoprotein | Casirivimab and Imdevimab | Hoffmann La Roche | Hoffmann La Roche | Intravenous | NA | NA | pain, bleeding, bruising of the skin, soreness, swelling, or infection at injection site | On January 24, 2022, FDA reissued the emergency use authorization (EUA) for casirivimab and imdevimab stating that the combination regimen is not authorized for treatment of mild to moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency. Given the prevalence of the Omicron variant in the United States, casirivimab and imdevimab is not recommended for use anywhere for mild to moderate disease at the present time. | to treat mild to moderate symptoms of COVID-19. to prevent COVID-19 in those who are not fully vaccinated against COVID-19 or who are vaccinated, but have a weakened immune system, or are taking a medication that affects the immune system and who have had close contact or are at high risk of close contact to someone who is infected with the SARS-CoV-2 virus (for example, nursing homes, prisons). | NA | NA | Link | Link | NA |
| 15984 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Approved Treatments for COVID-19 | NA | NA | NA | NA | Spike glycoprotein | Casirivimab With Imdevimab | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | NA | pain, bleeding, bruising of the skin, soreness, swelling, or infection at injection site | On January 24, 2022, FDA reissued the emergency use authorization (EUA) for casirivimab and imdevimab stating that the combination regimen is not authorized for treatment of mild to moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency. Given the prevalence of the Omicron variant in the United States, casirivimab and imdevimab is not recommended for use anywhere for mild to moderate disease at the present time. | to treat mild to moderate symptoms of COVID-19. to prevent COVID-19 in those who are not fully vaccinated against COVID-19 or who are vaccinated, but have a weakened immune system, or are taking a medication that affects the immune system and who have had close contact or are at high risk of close contact to someone who is infected with the SARS-CoV-2 virus (for example, nursing homes, prisons). | NA | NA | Link | Link | NA |
| 15985 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Blood Proteins | NA | NA | NA | NA | Spike glycoprotein | Regen-cov | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | None. | infusion-related reactions (hives, itching, flushing, fever, shortness of breath, chest tightness, nausea, vomiting, rash) and severe allergic reactions (anaphylaxis). | NA | Regen-Cov is a prescription medicine used to treat the symptoms of COVID-19 (EUA). Regen-Cov may be used alone or with other medications. | NA | Casirivimab, a human immunoglobulin G-1 (IgG1) monoclonal antibody (mAb), is a covalent heterotetramer consisting of 2 heavy chains and 2 light chains produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture and has an approximate molecular weight of 145.23 kDa. | Link | Link | NA |
| 15986 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Immunoglobulins | NA | NA | NA | NA | Spike glycoprotein | Regen-cov | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | NA | None. | infusion-related reactions (hives, itching, flushing, fever, shortness of breath, chest tightness, nausea, vomiting, rash) and severe allergic reactions (anaphylaxis). | NA | Regen-Cov is a prescription medicine used to treat the symptoms of COVID-19 (EUA). Regen-Cov may be used alone or with other medications. | NA | Casirivimab, a human immunoglobulin G-1 (IgG1) monoclonal antibody (mAb), is a covalent heterotetramer consisting of 2 heavy chains and 2 light chains produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture and has an approximate molecular weight of 145.23 kDa. | Link | Link | NA |
| 15987 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Immunoproteins | NA | NA | NA | NA | Spike glycoprotein | Ronapreve | Roche Registration Gmb H | Roche Registration Gmb H | Intravenous; Subcutaneous | NA | NA | The most common side effects with Ronapreve (which may affect up to 1 in 10 people) are allergic reactions, which include infusion related reactions and injection site reactions. | Ronapreve was found to be effective at preventing people from getting infected and developing symptoms after contact: amongst people who tested negative for SARS-CoV-2 following contact, fewer people given Ronapreve developed symptoms within 29 days of their test results compared with people given placebo (1.5% (11 out of 753) for Ronapreve compared with 7.8% (59 out of 752 people) for placebo). | Ronapreve is a medicine used for treating COVID-19 in adults and adolescents (from 12 years of age and weighing at least 40 kilograms) who do not require supplemental oxygen and who are at increased risk of their disease becoming severe. | NA | NA | Link | Link | NA |
| 15988 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Proteins | NA | NA | NA | NA | Spike glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15989 | Th1659 | Casirivimab | >Th1659_Casirivimab QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYITYSGSTIYYADSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCARDRGTTMVPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | NA | NA | NA | NA | NA | NA | Casirivimab is a monoclonal antibody combined with [Imdevimab] in Regeneron's antibody cocktail known as REGN-COV2 for the treatment of COVID-19.[L23539] This drug is a combination of antibodies derived from humanized VelocImmune® mice in addition to blood samples from patients who have recovered from COVID-19.[A224429] These antibodies have been formulated to bind to multiple locations on the SARS-COV-2 spike protein, preventing viral escape.[A221495] On November 21 2020, the FDA authorized emergency approval of REGEN-COV2 to treat mild to moderate COVID-19 in patients aged 12 years and older. Casirivimab and imdevimab are investigational recombinant human IgG1 monoclonal antibodies that, at this time, are not officially approved by the FDA. They are reserved for Emergency Use Authorization (EUA) only.[L23524] In November 2021, the same indication was approved by the EMA.[L39130,L39135] Full safety and efficacy data are not yet available, and further evaluation of this investigational therapy will continue.[L23539,L23529,L14303] | According to the Emergency Use Authorization (EUA) by the FDA and EMA, indevimab is used only with casirivimab to prevent COVID-19 and treat mild to moderate COVID-19 from laboratory-confirmed SARS-CoV-2 infection in patients aged 12 years of age and older who weigh at least 40 kg. Treatment is reserved for patients who are at high risk for progressing to require hospitalization or severe COVID-19.[L23524,L23534,L39135] This combination may only be administered by intravenous infusion in healthcare settings with immediate access to treatment for infusion reactions and anaphylaxis, and the ability to activate the emergency medical system (EMS), as required.[L23539,L23534] **Limitations of use** Imdevimab and casirivimab are not for use in patients currently hospitalized due to COVID-19, patients requiring oxygen therapy due to COVID-19, patients requiring increases in baseline oxygen flow rate from COVID-19, or patients on oxygen therapy for non-COVID-19 related morbidity.[L23524,L23534] | Casirivimab and imdevimab work to neutralize the spike protein of SARS-CoV-2.[L23524] In a clinical trial, casirivimab and imdevimab, when given together, reduced COVID-19-related hospitalization or emergency room visits in patients diagnosed with COVID-19 who were at high risk for disease progression within 28 days after treatment. No benefit has been shown in patients already hospitalized due to COVID-19 receiving this combination.[L23539] | Casirivimab is a recombinant human IgG1 monoclonal antibody targeting the receptor binding domain of the spike protein of SARS-CoV-2; a protein playing an important role in viral attachment, fusion, and entry into the cell.[A224434,L23529] Together with imdevimab, casirivimab neutralizes the spike protein of SARS-CoV-2.[L23529] | There is limited information on overdose. Up to 4000 mg, which is approximately seven times the recommended dose of the drug, was administered in clinical trials. There is no known specific antidote for casirivimab overdose so treatment of overdose should involve general supportive measures.[L39135] | NA | NA | NA | NA | Serum Globulins | NA | NA | NA | NA | Spike glycoprotein | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16180 | Th1693 | P113D | NA | NA | NA | NA | NA | NA | NA | P113D is a novel 12 amino-acid antimicrobial peptide drug derived from histatins, which are compounds found naturally in human saliva. It is being pursued as a potential treatment for cystic fibrosis by Demegen, Inc. | For the potential treatment of cystic fibrosis and bacterial infections. | P113D has demonstrated activity against CF patient clinical isolates of bacteria that are resistant to traditional antibiotics. The compound is stable and maintains activity in sputum of CF patients. P113 was determined to be the smallest histatin fragment which retained antimicrobial activity equivalent to that of the parent compound. Interestingly, synthesizing P113 with D-amino acids gave rise P113D, a compound that was impervious to enzymatic degradation and maintained the antimicrobial activity of the parent compound. P113D also has very potent in vitro activity against a variety of Gram negative and positive bacteria including P. aeruginosa, S. aureus, H. influenzae, S. typhimurium, E. coli, S. epidermidis, S. mutans and S. sobrinus. In the case of P. aeruginosa and S. aureus, antibacterial activity has been demonstrated against a variety of CF patient clinical isolates which are resistant to traditional antibiotics. P. aeruginosa isolates that produce thick alginate secretions (mucoid phenotype) are also susceptible to killing by P113D. | For both bacteria and fungi such as Candida albicans, P113D has been shown to kill cells as opposed to simply inhibiting their growth. It has been demonstrated that P113D acts by binding to the cell surface and increasing the permeability of both the outer and inner membranes of the cells of Gram negative bacteria, killing them within seconds. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16183 | Th1696 | LC16M8 | >Th1696_LC16M8 MEFDPAKINTSSIDHVTILQYIDEPNDIRLTVCIIRNINNITYYINITKINTHLANQFRAWKKRIAGRDYITNLSRDTGIQQSKLTETIRNCQKNRNIYGLYIHYNLVINVVIDWITDVIVQSILRGLVNWYIANNTYTPNNTTTISELDIIKILDKYEDVYRVSKEKECGICYEVVYSKRLENDRYFGLLDSCNHIFCITCINIWHKTRRETGASDNCPICRTRFRNITMSKFYKLVN | NA | NA | NA | NA | NA | NA | LC16m8 is a next-generation, attenuated smallpox vaccine that is designed to have a better safety profile, yet be equally effective, compared to conventional smallpox vaccines. It is the only attenuated vaccine to be licensed for use in humans to prevent smallpox infection. | Investigated for use/treatment in viral infection. | NA | LC16m8 is produced in cell culture from vaccinia virus that has been attenuated, or modified, so that it can initiate an immune response without causing serious adverse side effects. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16184 | Th1697 | MVA3000 | NA | NA | NA | NA | NA | NA | NA | MVA3000 is an attenuated smallpox vaccine that is being developed for use in people for whom the traditional smallpox vaccine is contraindicated, such as patients with disorders of the immune system or skin conditions such as eczema. | Investigated for use/treatment in viral infection. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16187 | Th1700 | VIR201 | NA | NA | NA | NA | NA | NA | NA | is an experimental therapeutic vaccine currently in clinical trial. The aim of therapeutic vaccines is to augment the body's immune response to HIV and to delay or prevent progression to AIDS. | Investigated for use/treatment in HIV infection. | NA | VIR201 uses DNA vaccine technology called Co-X-Gene in which HIV and human genetic material have been grafted on to a harmless fowlpox virus. This fowlpox vector carries genetic material for HIV proteins gag and pol. The aim of this component of the vaccine is to stimulate HIV-specific immune responses in people who have very low levels of HIV in their blood due to antiretroviral therapy. The vaccine also carries genetic material to stimulate the cytokine or immune system messenger called interferon gamma which is associated with delayed disease progression. The aim of this second component of the vaccine is to boost levels of interferon gamma and improve immune functioning. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16196 | Th1709 | KB001 | NA | NA | NA | NA | NA | NA | NA | KB001 is a Humaneered™ PEGylated monoclonal antibody fragment for the treatment of life-threatening Pseudomonas aeruginosa infections, a common problem of cystic fibrosis and mechanically ventilated patients. | For the treatment of infections caused by multi-drug resistant Pseudomonas aeruginosa. | KaloBios is developing KB001, a PEGylated engineered human Fab' fragment for the prevention and treatment of Pseudomonas aeruginosa infections. The Fab' fragment is specific for the PcrV antigen, an essential component of the Type III secretion system, a key virulence factor with multiple roles in both infection and pathogenesis. KB001 shows potent activity in mouse models of pulmonary infection, reducing mortality and leading to effective clearance of bacteria from infected lungs. This molecule therefore represents an attractive candidate for clinical evaluation in the prevention or treatment of Pseudomonas infection in Cystic Fibrosis, pneumonia, and other indications. | KB001 targets and neutralizes the PcrV protein of the Type III secretion system of the Pseudomonas bacterium, which directly inhibits its toxic effects. This mechanism of action is different from that of other antibiotics and represents a new approach in the treatment of bacterial infections. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | PcrV | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16198 | Th1711 | rhMBL | >Th1711_rhMBL MSLFPSLPLLLLSMVAASYSETVTCEDAQKTCPAVIACSSPGINGFPGKDGRDGTKGEKG | NA | NA | NA | NA | NA | NA | rhMBL is a protein therapeutic being developed by Enzon for the prevention and treatment of severe infections in individuals with low levels of Mannose-Binding Lectin (MBL). Over 10 percent of the general population is estimated to be MBL-deficient. Natural MBL is a 400-700kDa oligomer made of 3 identical 32kDa peptide chains. MBL forms different oligomers but must form at least a tetramer to be active. | Investigated for use/treatment in immunodeficiency and infectious and parasitic disease (unspecified). | NA | MBL deficiency may explain why some but not all individuals who are immunosuppressed develop infectious complications even when they receive prophylactic anti-infectious treatment. Studies have shown a correlation between low MBL levels and susceptibility to serious infections in patients immunosuppressed from chemotherapy, including patients with multiple myeloma undergoing high-dose chemotherapy and hematopoietic stem cell transplantation. rhMBL acts as natural MBL in the body, reducing susceptibility to serious infections. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16212 | Th1725 | PI-0824 | >Th1725_PI-0824 MMGLFPRTTGALAIFVVVILVHGELRIETKGQYDEEEMTMQQAKRRQKREWVKFAKPCREGEDNSKRNPIAKITSDYQATQKITYRISGVGIDQPPFGIFVVDKNTGDINITAIVDREETPSFLITCRALNAQGLDVEKPLILTVKILDINDNPPVFSQQIFMGEIEENSASNSLVMILNATDADEPNHLNSKIAFKIVSQEPAGTPMFLLSRNTGEVRTLTNSLDREQASSYRLVVSGADKDGEGLSTQCECNIKVKDVNDNFPMFRDSQYSARIEENILSSELLRFQVTDLDEEYTDNWLAVYFFTSGNEGNWFEIQTDPRTNEGILKVVKALDYEQLQSVKLSIAVKNKAEFHQSVISRYRVQSTPVTIQVINVREGIAFRPASKTFTVQKGISSKKLVDYILGTYQAIDEDTNKAASNVKYVMGRNDGGYLMIDSKTAEIKFVKNMNRDSTFIVNKTITAEVLAIDEYTGKTSTGTVYVRVPDFNDNCPTAVLEKDAVCSSSPSVVVSARTLNNRYTGPYTFALEDQPVKLPAVWSITTLNATSALLRAQEQIPPGVYHISLVLTDSQNNRCEMPRSLTLEVCQCDNRGICGTSYPTTSPGTRYGRPHSGRLGPAAIGLLLLGLLLLLLAPLLLLTCDCGAGSTGGVTGGFIPVPDGSEGTIHQWGIEGAHPEDKEITNICVPPVTANGADFMESSEVCTNTYARGTAVEGTSGMEMTTKLGAATESGGAAGFATGTVSGAASGFGAATGVGICSSGQSGTMRTRHSTGGTNKDYADGAISMNFLDSYFSQKAFACAEEDDGQEANDCLLIYDNEGADATGSPVGSVGCCSFIADDLDDSFLDSLGPKFKKLAEISLGVDGEGKEVQPPSKDSGYGIESCGHPIEVQQTGFVKCQTLSGSQGASALSTSGSVQPAVSIPDPLQHGNYLVTETYSASGSLVQPSTAGFDPLLTQNVIVTERVICPISSVPGNLAGPTQLRGSHTMLCTEDPCSRLI | NA | NA | NA | NA | NA | NA | Pemphigus vulgaris (PV) is an autoimmune disease affecting approximately 40,000 people worldwide. People with PV produce antibodies that attack the cells of the skin, resulting in blisters which, if left untreated, can lead to devastating infections and discomfort. Currently, most doctors who treat patients with PV will prescribe high-dose steroids and drugs that suppress the immune system in an effort to decrease the production of these antibodies. Unfortunately these medications are associated with serious and difficult side effects that often result in the discontinuation of their use. Peptimmune, Inc. has developed a new therapy for the treatment of PV, PI-0824. The goal of this therapy is to reduce the production of antibodies that cause PV blisters by acting only on the disease causing components of the immune system. It is hoped that use of PI-0824 will reduce or potentially eliminate the need for high dose steroids and drugs that suppress the immune system. | Investigated for use/treatment in autoimmune diseases and skin infections/disorders. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16220 | Th1733 | HGTV-43 | NA | NA | NA | NA | NA | NA | NA | HGTV43 is an anti-sense treatment designed to produce T cells that are genetically resistant to HIV infection. HGTV43 is one of a number of so-called 'gene transfer vectors' developed by the biotechnology company Enzo Biochem, Inc. | Investigated for use/treatment in HIV infection. | NA | HGTV43 works by 'turning off' the genes which HIV needs to grow and reproduce in human cells. Engineered genes are inserted directly into cells to regulate the function of the genes essential for HIV replication. These genetically modified CD4 cells are then transferred back to the individual. The theory is that these individuals will thus have a pool of fully functioning CD4 cells immune to HIV infection. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16238 | Th1751 | CCR5 mAb | >Th1751_CCR5_mAb MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKRLKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFIILLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSSHFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTIMIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFVGEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL | NA | NA | NA | NA | NA | NA | CCR5 mAb is a fully human monoclonal antibody that specifically recognizes and binds the chemokine receptor CCR5, which is known to be a key facilitator of infection with human immunodeficiency virus (HIV-1). It was generated by HGS using the Abgenix XenoMouse technology. | Investigated for use/treatment in HIV infection. | NA | The chemokine receptor CCR5 provides a portal of entry for HIV-1 and serves a target for potential new antiretroviral therapies. CCR5 monoclonal antibodies (mAb) and small-molecule CCR5 antagonists potently block HIV-1 entry in vitro, and controlled clinical trials have provided initial proof-of-concept for this mode of therapy. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | C-C chemokine receptor type 5 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16239 | Th1752 | MDX-1303 | NA | NA | NA | NA | NA | NA | NA | MDX-1303 is a fully human antibody against the inhalation anthrax, the most lethal form of illness in humans caused by the Bacillus anthracis bacterium, and targets a protein component of these lethal toxins known as the anthrax protective antigen. | Investigated for use/treatment in anthrax exposure and bacterial infection. | NA | MDX-1303 targets a protein component of lethal toxins produced by the bacterium known as the anthrax protective antigen. The anthrax protective antigen initiates the onset of the illness by attaching to cells in the infected person, and then facilitates the entry of additional destructive toxins into the cells. MDX-1303 is designed to target anthrax protective antigen and protect the cells from damage by the anthrax toxins. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Anthrax toxin receptor 2,Anthrax toxin receptor 1 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16293 | Th1803 | Bulevirtide | NA | NA | NA | NA | NA | NA | The half-life of bulevirtide ranges between 4 and 7 hours in healthy adults.[L30290] | Hepatitis D is considered the most severe type of viral hepatitis and leads to the rapid development of cirrhosis, severe decompensation of liver function, and an increased risk of mortality.[A226340,L30235] Until recently, there have been extremely limited treatments available for Hepatitis D infection.[A226305] Bulevirtide, also known as Hepcludex, is a first-in-class entry inhibitor for the treatment of chronic Hepatitis D infection developed by MYR Pharmaceuticals, now part of Gilead. It was first approved for use in the EU on May 28, 2020; bulevirtide has been granted PRIME scheme eligibility and Orphan Drug Designation by the European Medicines Agency.[L30215] In the USA, bulevirtide has been granted Orphan Drug Designation and Breakthrough Therapy Designation.[L30260,L30275] Due to potentially beneficial synergistic effects in treating chronic Hepatitis D, bulevirtide is also under investigation in clinical trial NCT03852433 (Phase 2b Study of Bulevirtide With [Peginterferon Alfa-2a]) in Patients With CHD. Completion of this clinical trial is anticipated in early 2023.[L30240] | Bulevirtide is indicated for the treatment of chronic Hepatitis D infection in HDV-RNA positive adult patients with compensated liver disease.[L30215] | Bulevirtide prevents Hepatitis D entry into cells. It is effective in the reduction of Hepatitis D virus (HDV) RNA levels and improvement of liver inflammation in cases of Hepatitis D infection.[L30215,L30220,L30260] | The sodium taurocholate co-transporting polypeptide (NTCP) serves to transport bile acids in the sodium salt form to the liver from the portal circulation. It is an important component of enterohepatic circulation. The Hepatitis D virus replicates independently within liver cells but requires the hepatitis B surface antigen in order to propagate. Hepatitis B and D viruses enter hepatocytes through the binding of NTCP (sodium/taurocholate cotransporting polypeptide) to the Hepatitis B virus preS1 surface protein domain.[L30260] Bulevirtide binds and subsequently inactivates the hepatitis B (HBV) and HDV receptors on hepatocytes. Bulevirtide blocks the NTCP binding site, subsequently blocking the entry of the viruses into cells. This prevents viral entry and replication, reducing symptoms of Hepatitis D infection.[L30260] | There are no reports of overdose with bulevirtide. In the case of an overdose, monitor the patient and provide supportive treatment.[L30290] | To date, metabolism studies have not been conducted on bulevirtide. It is expected to be catabolized by peptidases to smaller peptides and amino acids, with no active metabolites.[L30215,L30290] | Human pharmacokinetic data for bulevirtide is limited in the literature. In rats, bulevirtide administered by subcutaneous injection is rapidly absorbed with a Cmax of 4 to 6 hours.[L30215] The estimated bioavailability is 85% in humans, and steady-state concentrations are expected to occur within weeks of initiating treatment.[A226375,L30290] The AUC for bulevirtide after a 2mg subcutaneous dose was found to be approximately 46 ng/ml.h with a Tmax of 0.5 hours.[L30215] | The volume of distribution of bulevirtide is estimated to be lower than total body water.[L30290] In animals, bulevirtide distributes into the liver, gastrointestinal tract, kidney, and bladder.[L30215] | The clearance after of bulevirtide after subcutaneous administration (CL/F) in healthy volunteers ranged from 7.98 L/h (±2.02) to 62 L/h (±16.7), depending on the dose administered.[L30215] The clearance of bulevirtide decreases as the dose increases.[L30290] | NA | NA | NA | NA | NA | Sodium/bile acid cotransporter | Hepcludex | Gilead Sciences Ireland Uc | Gilead Sciences Ireland Uc | Subcutaneous | 2 mg | NA | The most common side effects with Hepcludex are raised levels of bile salts in the blood (which may affect more than 1 in 10 people) and reactions at the site of injection (which may affect up to 1 in 10 people). The most common serious side effect is worsening of liver disease after stopping Hepcludex (which may affect up to 1 in 10 people). | Hepcludex is an antiviral medicine used to treat chronic (long-term) hepatitis delta virus (HDV) infection in adults with compensated liver disease (when the liver is damaged but is still able to work), when the presence of viral RNA (genetic material) has been confirmed by blood tests. | N.Achronic (long-term) hepatitis delta virus (HDV) infection | NA | https://www.ema.europa.eu/en/medicines/human/EPAR/hepcludex | Link | Link | NA |
| 16380 | Th1890 | Bebtelovimab | >Th1890_Bebtelovimab QITLKESGPTLVKPTQTLTLTCTFSGFSLSISGVGVGWLRQPPGKALEWLALIYWDDDKRYSPSLKSRLTISKDTSKNQVVLKMTNIDPVDTATYYCAHHSISTIFDHWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144000.0 Da | NA | NA | NA | NA | Following a single intravenous dose of 175mg, the mean elimination half-life of bebtelovimab was 11.5 days | Bebtelovimab (LY-COV1404, LY-3853113) is a human monoclonal antibody approved for emergency use in the treatment of COVID-19. It binds to a portion of the SARS-CoV-2 spike (S) protein's receptor-binding domain, thereby preventing spike protein interaction with ACE2 and subsequent viral entry into host cells. Bebtelovimab is notable in that the epitope to which it binds appears infrequently mutated, making it a viable candidate for use in resistant SARS-CoV-2 strains (i.e. variants of concern, VOCs), including the B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants.1 This is in contrast to previously developed COVID-19 monoclonal antibody treatments - including bamlanivimab, etesevimab, casirivimab, and imdevimab - which have been found ineffective in the treatment of COVID-19 caused by the Omicron variant. | The FDA has issued an emergency use authorization (EUA) for the use of bebtelovimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients (≥12 years old and ≥40 kg) who are positive for SARS-CoV-2 infection, are at a high risk of progression to severe COVID-19, and for whom alternative treatment options are not accessible or clinically appropriate. | Bebtelovimab binds the SARS-CoV-2 spike protein with a dissocation constant KD = 0.046 - 0.075 nM and blocks spike protein attachment to the human ACE2 receptor with an IC50 value of 0.39 nM. | Bebtelovimab is a neutralizing human IgG1κ monoclonal antibody targeted against the spike (S) protein of SARS-CoV-2,2 which is responsible for facilitating viral entry into host cells. More specifically, bebtelovimab binds to an epitope of the S protein receptor-binding domain (RBD) which overlaps the ACE2-interacting site, effectively inhibiting the interaction between ACE2 and the S protein required for viral entry. | Single doses of up to 1750mg of bebtelovimab (10 times the authorized dose) have been administered in clinical trials without evidence of dose-limited toxicity. Treatment of bebtelovimab overdose should consist of general supportive measures. | As with other therapeutic proteins, bebtelovimab is likely degraded via catabolic processes into smaller peptides and amino acids. | Following a single intravenous dose of 175mg, the mean Cmax and AUCinf of bebtelovimab were 59.8 mcg/mL and 522 mcg.day/mL, respectively. | At steady-state, the volume of distribution of bebtelovimab is 4.61 L. | Following a single intravenous dose of 175mg, the mean clearance of bebtelovimab was 0.335 L/day. | Amino Acids, Peptides, and Proteins,Antibodies,Approved Treatments for COVID-19,Blood Proteins,Globulins,Immunoglobulins,Immunoproteins,Proteins,Serum Globulins | NA | NA | NA | NA | Spike glycoprotein | Bebtelovimab | Eli Lilly and Company | Eli Lilly and Company | Injection, solution | 87.5 mg/1mL | NA | fever difficulty breathing low oxygen level in your blood chills tiredness fast or slow heart rate chest discomfort or pain weakness confusion nausea headache shortness of breath low or high blood pressure wheezing swelling of your lips, face, or throat rash including hives itching muscle aches dizziness feeling faint, and sweating. | Bebtelovimab has not undergone the same type of review as an FDA-approved product. In issuing an EUA under the COVID-19 public health emergency, the FDA has determined, among other things, that based on the total amount of scientific evidence available, including data from adequate and well-controlled clinical trials, it is reasonable to believe that the product may be effective for diagnosing, treating, or preventing COVID-19, or a serious or life-threatening disease or condition caused by COVID-19; that the known and potential benefits of the product, when used to diagnose, treat, or prevent such disease or condition, outweigh the known and potential risks of such product; and that there are no adequate, approved and available alternatives. | Bebtelovimab is an investigational medicine used under Emergency Use Authorization (EUA) for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and children (12 years of age and older weighing at least 88 pounds [40 kg]) | NA | NA | Link | Link | NA |