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
10327	Th1046	Abciximab	>Th1046_Abciximab EVQLQQSGTVLARPGASVKMSCEASGYTFTNYWMHWVKQRPGQGLEWIGAIYPGNSDTSYIQKFKGKAKLTAVTSTTSVYMELSSLTNEDSAVYYCTLYDGYYVFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH	145651.1	C6462H9964N1690O2049S48	6.16	-0.424	71	initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes	Abciximab is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules. It also binds to vitronectin (ÃƒÅ½Ã‚Â±vÃƒÅ½Ã‚Â²3) receptor found on platelets and vessel wall endothelial and smooth muscle cells.	Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.	Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes.	Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/orconformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the ÃƒÅ½Ã‚Â±vÃƒÅ½Ã‚Â²3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion.	NA	Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally.	NA	NA	NA	Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Anticoagulants, Antiplatelet agents, Blood and Blood Forming Organs, Blood Proteins, Globulins, Hematologic Agents, Immunoglobulin Fab Fragments, Immunoglobulin Fragments, Immunoglobulins, Immunoproteins, Miscellaneous Therapeutic Agents, Peptide Fragments, Peptides, Platelet Aggregation Inhibitors Excl. Heparin, Proteins, Serum Globulins	CA1341357	7-May-2002	7-May-2019	Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided with Ginkgo biloba.	Integrin beta-3,Integrin alpha-IIb,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 immuno	ReoPro	Eli Lilly and Company, Janssen Pharmaceuticals, Janssen Biotech, Inc.	Eli Lilly and Company, Janssen Pharmaceuticals, Janssen Biotech, Inc.	ReoPro is used to lessen the chance of heart attack in people who need percutaneous coronary intervention (PCI), a procedure to open blocked arteries of the heart.	NA	Each single use vial contains 2 mg/mL of Abciximab in a buffered solution (pH 7.2) of 0.01 M sodium phosphate, 0.15 M sodium chloride and 0.001% polysorbate 80 in Water for Injection. No preservatives are added.	Clear, colorless, Sterile, non-pyrogenic solution	Intravenous administartion	The recommended dosage of Abciximab in adults is a 0.25 mg/kg intravenous bolus administered 10-60 minutes before the start of PCI, followed by a continuous Intravenous infusion of 0.125 _g/kg/min (to a maximum of 10 _g/min) for 12 hours.	Active internal bleeding, Recent (within six weeks) gastrointestinal (GI) or genitourinary (GU) bleeding of clinical significance, History of cerebrovascular accident (CVA) within two years, or CVA with a significant residual neurological deficit, Bleeding diathesis; Administration of oral anticoagulants within seven days unless prothrombin time is I 1.2 times control; Thrombocytopenia (< 100,000 cells/pL); Recent (within six weeks) major surgery or trauma; Intracranial neoplasm, arteriovenous malformation, or aneurysm; Severe uncontrolled hypertension; Presumed or documented history of vasculitis; Use of intravenous dextran before percutaneous coronary intervention, or intent to use it during an intervention.	Bleeding; blurred vision; confusion; dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly; sweating; unusual tiredness or weakness	Link	NA	NA
10328	Th1046	Abciximab	>Th1046_Abciximab EVQLQQSGTVLARPGASVKMSCEASGYTFTNYWMHWVKQRPGQGLEWIGAIYPGNSDTSYIQKFKGKAKLTAVTSTTSVYMELSSLTNEDSAVYYCTLYDGYYVFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH	145651.1	C6462H9964N1690O2049S48	6.16	-0.424	71	initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes	Abciximab is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules. It also binds to vitronectin (ÃƒÅ½Ã‚Â±vÃƒÅ½Ã‚Â²3) receptor found on platelets and vessel wall endothelial and smooth muscle cells.	Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.	Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes.	Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/orconformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the ÃƒÅ½Ã‚Â±vÃƒÅ½Ã‚Â²3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion.	NA	Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally.	NA	NA	NA	Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Anticoagulants, Antiplatelet agents, Blood and Blood Forming Organs, Blood Proteins, Globulins, Hematologic Agents, Immunoglobulin Fab Fragments, Immunoglobulin Fragments, Immunoglobulins, Immunoproteins, Miscellaneous Therapeutic Agents, Peptide Fragments, Peptides, Platelet Aggregation Inhibitors Excl. Heparin, Proteins, Serum Globulins	NA	NA	NA	Tirofiban has additive effects. Concomitant use is contraindicated.	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Black, tarry stools; bleeding gums; blood in urine or stools; pinpoint red spots on skin; unusual bleeding or bruising	Link	NA	NA
10329	Th1046	Abciximab	>Th1046_Abciximab EVQLQQSGTVLARPGASVKMSCEASGYTFTNYWMHWVKQRPGQGLEWIGAIYPGNSDTSYIQKFKGKAKLTAVTSTTSVYMELSSLTNEDSAVYYCTLYDGYYVFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH	145651.1	C6462H9964N1690O2049S48	6.16	-0.424	71	initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes	Abciximab is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules. It also binds to vitronectin (ÃƒÅ½Ã‚Â±vÃƒÅ½Ã‚Â²3) receptor found on platelets and vessel wall endothelial and smooth muscle cells.	Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.	Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes.	Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/orconformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the ÃƒÅ½Ã‚Â±vÃƒÅ½Ã‚Â²3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion.	NA	Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally.	NA	NA	NA	Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Anticoagulants, Antiplatelet agents, Blood and Blood Forming Organs, Blood Proteins, Globulins, Hematologic Agents, Immunoglobulin Fab Fragments, Immunoglobulin Fragments, Immunoglobulins, Immunoproteins, Miscellaneous Therapeutic Agents, Peptide Fragments, Peptides, Platelet Aggregation Inhibitors Excl. Heparin, Proteins, Serum Globulins	NA	NA	NA	Abciximab may increase the risk of a hypersensitivy reaction to Trastuzumab.	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Chest pain or discomfort; chills; cough; eye pain; fever; general feeling of illness; headache; pale skin; rapid weight gain; shortness of breath; slow or irregular heartbeat; sneezing; sore throat; swelling of hands, ankles, feet, or lower legs.	Link	NA	NA
10330	Th1046	Abciximab	>Th1046_Abciximab EVQLQQSGTVLARPGASVKMSCEASGYTFTNYWMHWVKQRPGQGLEWIGAIYPGNSDTSYIQKFKGKAKLTAVTSTTSVYMELSSLTNEDSAVYYCTLYDGYYVFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH	145651.1	C6462H9964N1690O2049S48	6.16	-0.424	71	initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes	Abciximab is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules. It also binds to vitronectin (ÃƒÅ½Ã‚Â±vÃƒÅ½Ã‚Â²3) receptor found on platelets and vessel wall endothelial and smooth muscle cells.	Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.	Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes.	Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/orconformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the ÃƒÅ½Ã‚Â±vÃƒÅ½Ã‚Â²3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion.	NA	Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally.	NA	NA	NA	Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Anticoagulants, Antiplatelet agents, Blood and Blood Forming Organs, Blood Proteins, Globulins, Hematologic Agents, Immunoglobulin Fab Fragments, Immunoglobulin Fragments, Immunoglobulins, Immunoproteins, Miscellaneous Therapeutic Agents, Peptide Fragments, Peptides, Platelet Aggregation Inhibitors Excl. Heparin, Proteins, Serum Globulins	NA	NA	NA	The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Abciximab. Monitor for increased bleeding during concomitant thearpy.	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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-1 [A33079].	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
11870	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11871	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11872	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11873	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11874	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Biochemical Phenomena	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11875	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11876	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11877	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Immunoglobulin Fab Fragments	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11878	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Immunoglobulin Fragments	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11879	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Immunoglobulin Variable Region	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11880	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11881	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11882	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Information Science	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11883	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Information Services	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11884	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Molecular Sequence Data	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11885	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Molecular Structure	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11886	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	NA	NA	NA	NA	NA	Peptide Fragments	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
11887	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11888	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
11889	Th1264	Pexelizumab	>Th1264_Pexelizumab MADIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQRKPGKAPKLLIYGATNLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTGGGGSGGGGSGGGGSQVQLVQSGAEVEKPGASVKKVSCKASGYIFSNYWIQWVRQAPGQGLEWMGEILPGSGSTEYAQKFQGRVTMTADTSTSTAYMELSSLRSEDTAVYYCARYFFGSSPNYWYFDVWGQGTLVTVSS	NA	NA	NA	NA	NA	7.0 hours to 14.5 hours.	Pexelizumab is a humanized monoclonal antibody used as an immunosuppressive drug. It is being investigated by Alexion Pharmaceuticals.	For the treatment of inflammation during cardiac surgery.	Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms.	Although inflammation is a normal response, continued exposure to foreign surfaces, toxic antigens, and tissue injury results in pathologic local and systemic inflammation (SIRS). This response involves multiple humoral and cellular components, including the coagulation (Factor XII, thrombin, Proteins C and S, platelets) and complement systems, cytokines (TNF-alpha, interleukins), leukocytes, monocytes, adhesion molecules (ICAM-1), and endothelial cells, among others. The complement system is a group of glycoproteins, which, when activated, results in the formation of C3-convertase, which converts C3 to C3a and C3b. C3a cleaves C5 to C5a and C5b. C5b, in conjunction with C6, C7, C8, and C9, forms the membrane attack or terminal complement complex (TCC) C5b-9. Both C5a and C5b-9 activate, promote, and amplify inflammatory components, and likely play central roles in the development of SIRS, tissue injury, reperfusion injury, and apoptosis. Pexelizumab, a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9.	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
13130	Th1384	Albumin iodinated I-131 serum	NA	NA	NA	NA	NA	NA	NA	Iodinated I-131 serum albumin is a radiopharmaceutical agent used for several diagnostic purposes, including the determination of body fluid volumes and the imaging of certain tissues.[L12783]	Iodinated I-131 albumin is indicated for use in determinations of total blood and plasma volumes, cardiac output, cardiac and pulmonary blood volumes and circulation times, and in protein turnover studies, heart and great vessel delineation, localization of the placenta, and localization of cerebral neoplasms.[L12783]	NA	NA	NA	NA	NA	NA	NA	Radiopharmaceutical Activity	NA	NA	NA	NA	NA	Megatope	Iso-Tex Diagnostics, Inc.	Iso-Tex Diagnostics, Inc.	Intravenous	1 mCi/1mL	None Known.	allergic reactions	NA	Megatope (Iodinated I 131 Albumin Injection) is indicated for use in determinations of total blood and plasma volumes, cardiac output, cardiac and pulmonary blood volumes and circulation times, and in protein turnover studies, heart and great vessel dilineation, localization of the placenta, and localization of celebral neospasms.	NA	TABLE 1	Link	Link	NA
13131	Th1384	Albumin iodinated I-131 serum	NA	NA	NA	NA	NA	NA	NA	Iodinated I-131 serum albumin is a radiopharmaceutical agent used for several diagnostic purposes, including the determination of body fluid volumes and the imaging of certain tissues.[L12783]	Iodinated I-131 albumin is indicated for use in determinations of total blood and plasma volumes, cardiac output, cardiac and pulmonary blood volumes and circulation times, and in protein turnover studies, heart and great vessel delineation, localization of the placenta, and localization of cerebral neoplasms.[L12783]	NA	NA	NA	NA	NA	NA	NA	Radiopharmaceutical Activity	NA	NA	NA	NA	NA	Volumex	Iso-Tex Diagnostics, Inc.	Iso-Tex Diagnostics, Inc.	Intravenous	0.025 mCi/1mL	NA	Ã¯Â»Â¿Although the immunological properties of albumin human are believed to be virtuallyÃ‚Â unaltered by the iodination process, there is a theoretical possibility that allergic reactions may occur in patients receiving additional doses a number of weeks after an initial dose.	NA	NA	NA	NA	Link	Link	NA
13132	Th1385	Technetium Tc-99m red blood cells	NA	NA	NA	NA	NA	NA	Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours. The technetium Tc 99m is well retained in the blood pool with an estimated biological half-life of approximately 29 hours [FDA Label].	Technetium Tc-99m red blood cells is a radiopharmaceutical diagnostic agent that is intravenously administered to be used in blood pool imaging, including cardiac first pass and gated equilibrium imaging and for detection of sites of gastrointestinal bleeding. It is clinically useful in early detection and localization of bleeding sites, and preoperative diagnosis of hemangioma [A32178, A32179]. Autologous red blood cells are radiolabeled with sodium pertechnetate Tc 99m in the reaction vial. Radiolabeled red blood cells are re-injected intravenously into the patient for gamma scintigraphic imaging [FDA Label]. It is suggested that _in vitro_ labelling improves the heart-to-background ratio during imaging [A32181].	Indicated for blood pool imaging, including cardiac first pass and gated equilibrium imaging and for detection of sites of gastrointestinal bleeding [FDA Label].	Technetium Tc-99m red blood cells are diagnostic agents that are distributed within the circulation to assess the vascular nature of hemangiomas and diagnosis of venous occlusion [A32186]. Blood abnormalities can be detected during gamma scintigraphic imaging.	Autologous red blood cells (RBC) are collected from the patient and put into the reaction vial for radiolabeling, followed by anticoagulation with heparin or Anticoagulant Citrate Dextrose Solution (ACD). In the reaction vial, stannous ion diffuses across the RBC membrane and accumulates intracellularly. Sodium hypochlorite, which does not cross the RBC membrane, is then added to the reaction vial to oxidize the extracellular stannous ion. Finally, sodium pertechnetate Tc 99m is added to the oxidized reaction vial to diffuse across the red blood cell membrane and be reduced by the intracellular stannous ion. Upon reduction, Tc 99m cannot diffuse out of the RBC. Technetium Tc 99m-labeled red blood cells are injected again into the patient for gamma scintigraphic imaging [FDA Label].	No long term animal studies have been performed to evaluate carcinogenic or mutagenic potential or to determine the effects on male or female fertility [FDA Label].	NA	NA	Following intravenous injection, the technetium Tc 99m-labeled red blood cells distribute within the blood pool with an estimated volume of distribution of approximately 5.6% of bodyweight [FDA Label].	NA	Radioactive Diagnostic Agent	NA	NA	NA	NA	NA	UltraTag RBC	Mallinckrodt	Mallinckrodt	Intravenous	0.05 mg/9.5mg	None known.	NA	NA	Technetium Tc 99m-labeled red blood cells are used for blood pool imaging, including cardiac first pass and gated equilibrium imaging and for detection of sites of gastrointestinal bleeding.	NA	1. A 10 milliliter reaction vial containing:	Link	NA	NA
13133	Th1385	Technetium Tc-99m red blood cells	NA	NA	NA	NA	NA	NA	Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours. The technetium Tc 99m is well retained in the blood pool with an estimated biological half-life of approximately 29 hours [FDA Label].	Technetium Tc-99m red blood cells is a radiopharmaceutical diagnostic agent that is intravenously administered to be used in blood pool imaging, including cardiac first pass and gated equilibrium imaging and for detection of sites of gastrointestinal bleeding. It is clinically useful in early detection and localization of bleeding sites, and preoperative diagnosis of hemangioma [A32178, A32179]. Autologous red blood cells are radiolabeled with sodium pertechnetate Tc 99m in the reaction vial. Radiolabeled red blood cells are re-injected intravenously into the patient for gamma scintigraphic imaging [FDA Label]. It is suggested that _in vitro_ labelling improves the heart-to-background ratio during imaging [A32181].	Indicated for blood pool imaging, including cardiac first pass and gated equilibrium imaging and for detection of sites of gastrointestinal bleeding [FDA Label].	Technetium Tc-99m red blood cells are diagnostic agents that are distributed within the circulation to assess the vascular nature of hemangiomas and diagnosis of venous occlusion [A32186]. Blood abnormalities can be detected during gamma scintigraphic imaging.	Autologous red blood cells (RBC) are collected from the patient and put into the reaction vial for radiolabeling, followed by anticoagulation with heparin or Anticoagulant Citrate Dextrose Solution (ACD). In the reaction vial, stannous ion diffuses across the RBC membrane and accumulates intracellularly. Sodium hypochlorite, which does not cross the RBC membrane, is then added to the reaction vial to oxidize the extracellular stannous ion. Finally, sodium pertechnetate Tc 99m is added to the oxidized reaction vial to diffuse across the red blood cell membrane and be reduced by the intracellular stannous ion. Upon reduction, Tc 99m cannot diffuse out of the RBC. Technetium Tc 99m-labeled red blood cells are injected again into the patient for gamma scintigraphic imaging [FDA Label].	No long term animal studies have been performed to evaluate carcinogenic or mutagenic potential or to determine the effects on male or female fertility [FDA Label].	NA	NA	Following intravenous injection, the technetium Tc 99m-labeled red blood cells distribute within the blood pool with an estimated volume of distribution of approximately 5.6% of bodyweight [FDA Label].	NA	Radiopharmaceutical Activity	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
15101	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Amino Acids, Peptides, and Proteins	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	Beriplex P/n 1000	Csl Behring	Csl Behring	Intravenous	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
15102	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Biological Factors	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	Beriplex P/n 500	Csl Behring	Csl Behring	Intravenous	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
15103	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Blood and Blood Forming Organs	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	Feiba Vh Immuno Anti Inhibitor	Osterreichisches Institut Fur Haemoderivate Ges M.B.H.	Osterreichisches Institut Fur Haemoderivate Ges M.B.H.	Intravenous	NA	Known anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components, including factors of the kinin generating system. Disseminated intravascular coagulation (DIC). Acute thrombosis or embolism (including myocardial infarction).	headache flushing pain around the IV needle numbness or tingling, especially in your faceV	NA	NA	NA	NA	Link	Link	NA
15104	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Blood Coagulation Factors	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	Kcentra	CSL Behring GmbH	CSL Behring GmbH	Intravenous	NA	Kcentra is contraindicated in: Patients with known anaphylactic or severe systemic reactions to Kcentra or any components in Kcentra including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and Human albumin. Patients with disseminated intravascular coagulation (DIC). Patients with known heparin-induced thrombocytopenia (HIT). Kcentra contains heparin [see DESCRIPTION].	headache, nausea, vomiting, joint pain, low blood pressure (hypotension), and low levels of iron in the blood (anemia)	Kcentra is a blood coagulation factor replacement product. Kcentra is used to quickly reverse the effects of a blood-thinning medicine (such as warfarin) during a major bleeding episode, or when there is a need for emergency surgery or invasive medical procedure. Kcentra is for use in adults and dosing...	Kcentra is a prescription medicine used to treat the symptoms of Vitamin K Antagonist Reversal. Kcentra may be used alone or with other medications.	NA	NA	Link	Link	NA
15105	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Blood Proteins	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	Octaplex	Octapharma Pharmazeutika Produktionsges M B H	Octapharma Pharmazeutika Produktionsges M B H	Intravenous	NA	NA	Immune system disorders; General disorders and administration site conditions; Vascular disorders; Nervous system disorders;	NA	NA	NA	NA	Link	Link	NA
15106	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Enzyme Precursors	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
15107	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Enzymes and Coenzymes	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
15108	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Hemostatics	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
15109	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Increased Coagulation Activity	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
15110	Th1566	Coagulation factor VII human	>Th1566_Coagulation_factor_VII_human MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP	NA	NA	NA	NA	NA	5 h	Coagulation factor VII is human serine protease type enzyme that is involved in the extrinsic coagulation cascade which results in blood clotting.	May be administered in cases of uncontrolled bleeding. Factor VII alone can be used in the treatment of congenital hemophilia A or B, acquired hemophilia, congenital factor VII deficiency, and Glanzmann's thrombasthenia. Off label use in the treatment of refractory bleeding after cardiac surgery and warfarin related intracerebral hemorrhage. Brands for human factor VII are currently only in combination with other vitamin K coagulation factors and can be used to reverse vitamin K antagonist activity in patients with acute major bleeds or for urgent surgery/invasive procedures.	Human Factor VII complexes with tissue factor resulting in its activation to VIIa. It is the activated Factor VIIa that then binds to Factor X activating it to Factor Xa, as well as coagulation Factor IX is activated to Factor IXa. Factor Xa continues the coagulation cascade to eventually convert prothrombin to thrombin, which leads to the formation of a clot by converting fibrinogen to fibrin.	Factor VII is required in the extrinsic clotting cascade. When there is vascular damage tissue factor (TF) is released which then interacts with Factor VII resulting in the formation of the activated complex VIIa. Factor VIIa then continues to activate coagulation factors in the cascade until a clot is formed.	No evidence of toxicity. Adverse effect of excessive clotting in certain individuals.	Degraded by catabolism	No absorption since given IV.	45 ml/kg	7.4 ml/kgh	Proteins	NA	NA	NA	NA	Tissue factor,Coagulation factor X,Coagulation factor IX	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
16216	Th1729	FX06	>Th1729_FX06 MKHLLLLLLCVFLVKSQGVNDNEEGFFS	NA	NA	NA	NA	NA	NA	FX06 is a naturally occurring peptide derived from the neo-N-terminus of fibrin (Bbeta(15-42)). It prevents leukocyte migration through the gap junctions of endothelial cells. FX06 has proven safe in acute and subchronic toxicological studies and recently entered clinical development. It is being developed by Fibrex Medical Inc.	Investigated for use/treatment in cardiac reperfusion injury and myocardial infarction.	NA	FX06 has a novel mechanism of action: it is a competitive inhibitor of the binding of fibrin E1 fragments to vascular endothelial (VE)-cadherin. Through this inhibition, it potently blocks the transmigration of inflammatory leukocytes through the endothelial barrier and prevents the downstream release of tissue-damaging mediators.	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Cadherin-5	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Link	NA	NA
16243	Th1756	ACY001	NA	NA	NA	NA	NA	NA	NA	0	Investigated for use/treatment in cardiac ischemia and cardiovascular disorders.	NA	Hemangioblasts are stem cells which can differentiate into hematopoietic cells (blood cells)and angiogenic (blood vessel endothelium forming) cells. These cells are being investigated for use in repairing damaged cardiac tissue and preventing the deteriation of the retina in diabetic retinopathy.	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

IIITD

Raghava's Group