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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.
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| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 10022 | Th1003 | Dornase alfa | >Th1003_Dornase_alfa LKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQEVRDSHLTAVGKLLDNLNQDAPDTYHYVVSEPLGRNSYKERYLFVYRPDQVSAVDSYYYDDGCEPCGNDTFNREPAIVRFFSRFTEVREFAIVPLHAAPGDAVAEIDALYDVYLDVQEKWGLEDVMLMGDFNAGCSYVRPSQWSSIRLWTSPTFQWLIPDSADTTATPTHCAYDRIVVAGMLLRGAVVPDSALPFNFQAAYGLSDQLAQAISDHYPVEVMLK | 29253.9 | C1321H1999N339O396S9 | 4.58 | -0.083 | 67 | NA | It is a biosynthetic form of human enzyme DNase I, produced in genetically modified CHO cells using recombinant DNA technology. The 260 amino acid synthetic sequence of dornase alfa is identical to the endogenous human enzyme. Dornase alfa cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products(without affecting intracellular DNA). In individuals with cystic fibrosis, extracellular DNA, an extremely viscous anion, is released by degenerating leukocytes which accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA causes reduction in sputum viscosity and viscoelasticity. | Used in the treatment of cystic fibrosis as adjunct therapy. | Cystic fibrosis (CF) is characterized by retention of viscous purulent secretions in the airways. These thick secretions contribute to reduced pulmonary function and to frequent pulmonary infection. Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections. Dornase alfa hydrolyzes the DNA in sputum of CF patients and reduces sputum viscosity and viscoelasticity. The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection, nor does it affect the sputum of healthy individuals. | Dornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products. It has no effect on intracellular DNA. Optimal activity dependent on the presence of divalent cations such as calcium and magnesium. Extracellular DNA is a viscous anionic polymer and its breakdown appears to improve the viscosity and viscoelasticity of purulent sputum of individuals with CF. | Adverse reactions occur at a rate of 1/1000 and are usually mild and transient in nature. Reported adverse effects include decreased lung function, rash, urticaria, chest pain (pleuritic/non-cardiac), dyspepsia, voice alteration (hoarseness), pharyngitis | NA | Systemic absorption is undetectable when administered via inhalation. | NA | NA | Amino Acids, Peptides, and Proteins, Cough and Cold Preparations, Decreased Respiratory Secretion Viscosity, Deoxyribonucleases, Endodeoxyribonucleases, Endonucleases, Enzymes, Enzymes and Coenzymes, Esterases, Expectorants, Hydrolases, Proteins, Recombinant Human Deoxyribonuclease 1 | CA2184581 | 22-Feb-2005 | 28-Feb-2015 | Afrezza (insulin inhalation, rapid acting) | DNA | Pulmozyme | Genentech Inc | Genentech Inc | Pulmozyme is used to improve lung function by thinning pulmonary secretions and reducing the risk of respiratory tract infections in people with cystic fibrosis. | NA | The aqueous formulation contains 1.0 mg/mL dornase alfa, 0.15 mg/mL calcium chloride dihydrate and 8.77 mg/mL sodium chloride. The solution contains no preservative and supports a pH of 6.3. | NA | Administered by inhalation of an aerosol mist prod | NA | allergic | Serious side effects include difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives; increased difficulty breathing; chest pain; or fever. Less serious side effects may be voice alteration; sore throat; rash. | Link | NA | NA |
| 10023 | Th1003 | Dornase alfa | >Th1003_Dornase_alfa LKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQEVRDSHLTAVGKLLDNLNQDAPDTYHYVVSEPLGRNSYKERYLFVYRPDQVSAVDSYYYDDGCEPCGNDTFNREPAIVRFFSRFTEVREFAIVPLHAAPGDAVAEIDALYDVYLDVQEKWGLEDVMLMGDFNAGCSYVRPSQWSSIRLWTSPTFQWLIPDSADTTATPTHCAYDRIVVAGMLLRGAVVPDSALPFNFQAAYGLSDQLAQAISDHYPVEVMLK | 29253.9 | C1321H1999N339O396S9 | 4.58 | -0.083 | 67 | NA | It is a biosynthetic form of human enzyme DNase I, produced in genetically modified CHO cells using recombinant DNA technology. The 260 amino acid synthetic sequence of dornase alfa is identical to the endogenous human enzyme. Dornase alfa cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products(without affecting intracellular DNA). In individuals with cystic fibrosis, extracellular DNA, an extremely viscous anion, is released by degenerating leukocytes which accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA causes reduction in sputum viscosity and viscoelasticity. | Used in the treatment of cystic fibrosis as adjunct therapy. | Cystic fibrosis (CF) is characterized by retention of viscous purulent secretions in the airways. These thick secretions contribute to reduced pulmonary function and to frequent pulmonary infection. Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections. Dornase alfa hydrolyzes the DNA in sputum of CF patients and reduces sputum viscosity and viscoelasticity. The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection, nor does it affect the sputum of healthy individuals. | Dornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products. It has no effect on intracellular DNA. Optimal activity dependent on the presence of divalent cations such as calcium and magnesium. Extracellular DNA is a viscous anionic polymer and its breakdown appears to improve the viscosity and viscoelasticity of purulent sputum of individuals with CF. | Adverse reactions occur at a rate of 1/1000 and are usually mild and transient in nature. Reported adverse effects include decreased lung function, rash, urticaria, chest pain (pleuritic/non-cardiac), dyspepsia, voice alteration (hoarseness), pharyngitis, | NA | Systemic absorption is undetectable when administered via inhalation. | NA | NA | Amino Acids, Peptides, and Proteins, Cough and Cold Preparations, Decreased Respiratory Secretion Viscosity, Deoxyribonucleases, Endodeoxyribonucleases, Endonucleases, Enzymes, Enzymes and Coenzymes, Esterases, Expectorants, Hydrolases, Proteins, Recombinant Human Deoxyribonuclease 1 | NA | NA | NA | Exubera (insulin inhalation, rapid acting) | NA | NA | Cardinal Health, Catalent Pharma Solutions, F Hoffmann-La Roche Ltd., Meda AB, Medpointe Pharmaceuticals | Cardinal Health, Catalent Pharma Solutions, F Hoffmann-La Roche Ltd., Meda AB, Medpointe Pharmaceuticals | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10024 | Th1003 | Dornase alfa | >Th1003_Dornase_alfa LKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQEVRDSHLTAVGKLLDNLNQDAPDTYHYVVSEPLGRNSYKERYLFVYRPDQVSAVDSYYYDDGCEPCGNDTFNREPAIVRFFSRFTEVREFAIVPLHAAPGDAVAEIDALYDVYLDVQEKWGLEDVMLMGDFNAGCSYVRPSQWSSIRLWTSPTFQWLIPDSADTTATPTHCAYDRIVVAGMLLRGAVVPDSALPFNFQAAYGLSDQLAQAISDHYPVEVMLK | 29253.9 | C1321H1999N339O396S9 | 4.58 | -0.083 | 67 | NA | It is a biosynthetic form of human enzyme DNase I, produced in genetically modified CHO cells using recombinant DNA technology. The 260 amino acid synthetic sequence of dornase alfa is identical to the endogenous human enzyme. Dornase alfa cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products(without affecting intracellular DNA). In individuals with cystic fibrosis, extracellular DNA, an extremely viscous anion, is released by degenerating leukocytes which accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA causes reduction in sputum viscosity and viscoelasticity. | Used in the treatment of cystic fibrosis as adjunct therapy. | Cystic fibrosis (CF) is characterized by retention of viscous purulent secretions in the airways. These thick secretions contribute to reduced pulmonary function and to frequent pulmonary infection. Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections. Dornase alfa hydrolyzes the DNA in sputum of CF patients and reduces sputum viscosity and viscoelasticity. The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection, nor does it affect the sputum of healthy individuals. | Dornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products. It has no effect on intracellular DNA. Optimal activity dependent on the presence of divalent cations such as calcium and magnesium. Extracellular DNA is a viscous anionic polymer and its breakdown appears to improve the viscosity and viscoelasticity of purulent sputum of individuals with CF. | Adverse reactions occur at a rate of 1/1000 and are usually mild and transient in nature. Reported adverse effects include decreased lung function, rash, urticaria, chest pain (pleuritic/non-cardiac), dyspepsia, voice alteration (hoarseness), pharyngitis, | NA | Systemic absorption is undetectable when administered via inhalation. | NA | NA | Amino Acids, Peptides, and Proteins, Cough and Cold Preparations, Decreased Respiratory Secretion Viscosity, Deoxyribonucleases, Endodeoxyribonucleases, Endonucleases, Enzymes, Enzymes and Coenzymes, Esterases, Expectorants, Hydrolases, Proteins, Recombinant Human Deoxyribonuclease 1 | CA2137237 | 26-Oct-2004 | 28-May-2013 | NA | NA | Viscozyme | Roche (Chile) | Roche (Chile) | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10205 | Th1027 | Insulin Regular | >Th1027_Insulin_Regular GIVEQCCTSICSLYQLENYCN | 5808 | C257H383N65O77S6 | 5.39 | 0.218 | 81 | 2-3.4 hours | Insulin regular is a 51 residue peptide hormone, composed of two amino acid chains covalently linked by disulfide bonds. The structure is identical to native human insulin. Recombinant insulin is synthesized by recombinant DNA techncology. Inserting the human insulin gene into the Escherichia coli bacteria or Saccharomyces cerevisiae produces insulin for human use. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 1 and type 2 diabetes mellitus. | Insulin regular is a short-acting insulin. When subcutaneously administered, the onset of action (as evidenced by a decrease in glucose level) occurs 30 minutes post-dose. Maximal effect occurs between 1.5 and 3.5 hours post-dose. The glucose-lowering effect occurs 8 hours post-dose. Compared to other rapid-acting insulin analogs, insulin regular has a slower onset of action and longer duration of action. | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism. | Hypoglycemia is caused due to insulin toxicity. | Predominantly cleared by metabolic degradation via a receptor-mediated process. | Generally well absorbed. | 0.15 L/kg | NA | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin, metabolism, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | Liraglutide's coadministration may increase the risk of hypoglycemia. A lower dose of the antidiabetic agent may be needed. | Insulin receptor,Insulin-like growth factor 1 receptor,Retinoblastoma-associated protein,Cathepsin D,Insulin-degrading enzyme,Neuroendocrine convertase 2,Carboxypeptidase E,Neuroendocrine convertase 1,Protein NOV homolog,Low-density lipoprotein receptor-r | Humulin R | Eli Lilly and Company | Eli Lilly and Company | Treating diabetes mellitus. | NA | It contains human insulin (rDNA origin) 100 units/mL, glycerin 16 mg/mL and metacresol 2.5 mg/mL, endogenous zinc (approximately 0.015 mg/100 units) and water for injection. The pH is 7.0 to 7.8. Sodiumhydroxide and/or hydrochloric acid may be added durin | Sterile, clear, aqueous, and colorless solution | Subcutaneous Injection in the abdominal wall, the | Humulin R (insulin (human recombinant)) U-100, when used subcutaneously, is usually given three or more times daily before meals. The average range of total daily insulin requirement for maintenance therapy in insulin-treated patients without severe insulin resistance lies between 0.5 and 1 unit/kg/day. | During episodes of hypoglycemia and in patients hypersensitive to humulin R. | Rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; wheezing; muscle pain; changes in vision; chills; confusion; dizziness; drowsiness; fainting; fast or irregular heartbeat; headache; loss of apetite. | Link | NA | NA |
| 10206 | Th1027 | Insulin Regular | >Th1027_Insulin_Regular GIVEQCCTSICSLYQLENYCN | 5808 | C257H383N65O77S6 | 5.39 | 0.218 | 81 | 2-3.4 hours | Insulin regular is a 51 residue peptide hormone, composed of two amino acid chains covalently linked by disulfide bonds. The structure is identical to native human insulin. Recombinant insulin is synthesized by recombinant DNA techncology. Inserting the human insulin gene into the Escherichia coli bacteria or Saccharomyces cerevisiae produces insulin for human use. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 1 and type 2 diabetes mellitus. | Insulin regular is a short-acting insulin. When subcutaneously administered, the onset of action (as evidenced by a decrease in glucose level) occurs 30 minutes post-dose. Maximal effect occurs between 1.5 and 3.5 hours post-dose. The glucose-lowering effect occurs 8 hours post-dose. Compared to other rapid-acting insulin analogs, insulin regular has a slower onset of action and longer duration of action. | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism. | Hypoglycemia is caused due to insulin toxicity. | Predominantly cleared by metabolic degradation via a receptor-mediated process. | Generally well absorbed. | 0.15 L/kg | NA | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin, metabolism, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | NA | NA | ACTRAPID INJECTION 100 IU/ml | NOVO NORDISK PHARMA (SINGAPORE) PTE LTD | NOVO NORDISK PHARMA (SINGAPORE) PTE LTD | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10207 | Th1027 | Insulin Regular | >Th1027_Insulin_Regular GIVEQCCTSICSLYQLENYCN | 5808 | C257H383N65O77S6 | 5.39 | 0.218 | 81 | 2-3.4 hours | Insulin regular is a 51 residue peptide hormone, composed of two amino acid chains covalently linked by disulfide bonds. The structure is identical to native human insulin. Recombinant insulin is synthesized by recombinant DNA techncology. Inserting the human insulin gene into the Escherichia coli bacteria or Saccharomyces cerevisiae produces insulin for human use. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 1 and type 2 diabetes mellitus. | Insulin regular is a short-acting insulin. When subcutaneously administered, the onset of action (as evidenced by a decrease in glucose level) occurs 30 minutes post-dose. Maximal effect occurs between 1.5 and 3.5 hours post-dose. The glucose-lowering effect occurs 8 hours post-dose. Compared to other rapid-acting insulin analogs, insulin regular has a slower onset of action and longer duration of action. | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism. | Hypoglycemia is caused due to insulin toxicity. | Predominantly cleared by metabolic degradation via a receptor-mediated process. | Generally well absorbed. | 0.15 L/kg | NA | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin, metabolism, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | NA | NA | INSULATARD INJECTION 100 iu/ml | NOVO NORDISK PHARMA (SINGAPORE) PTE LTD | NOVO NORDISK PHARMA (SINGAPORE) PTE LTD | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10208 | Th1027 | Insulin Regular | >Th1027_Insulin_Regular GIVEQCCTSICSLYQLENYCN | 5808 | C257H383N65O77S6 | 5.39 | 0.218 | 81 | 2-3.4 hours | Insulin regular is a 51 residue peptide hormone, composed of two amino acid chains covalently linked by disulfide bonds. The structure is identical to native human insulin. Recombinant insulin is synthesized by recombinant DNA techncology. Inserting the human insulin gene into the Escherichia coli bacteria or Saccharomyces cerevisiae produces insulin for human use. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 1 and type 2 diabetes mellitus. | Insulin regular is a short-acting insulin. When subcutaneously administered, the onset of action (as evidenced by a decrease in glucose level) occurs 30 minutes post-dose. Maximal effect occurs between 1.5 and 3.5 hours post-dose. The glucose-lowering effect occurs 8 hours post-dose. Compared to other rapid-acting insulin analogs, insulin regular has a slower onset of action and longer duration of action. | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism. | Hypoglycemia is caused due to insulin toxicity. | Predominantly cleared by metabolic degradation via a receptor-mediated process. | Generally well absorbed. | 0.15 L/kg | NA | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin, metabolism, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | NA | NA | Novolin R | Novo Nordisk | Novo Nordisk | Used for the treatment of patients with diabetes mellitus, for the control of hyperglycemia | NA | It contains human insulin (rDNA origin) 100 units/mL, glycerol 16 mg/mL, metacresol 3 mg/mL, zinc chloride approximately 7 mcg/mL and water for injection. The pH is adjusted to 7.4. Hydrochloric acid 2N or sodium hydroxide 2N may be added to adjust pH. No | Sterile, clear, aqueous, and colorless solution | Subcutaneous and Intravenous infusion | The injection of Novolin R (recombinant dna origin) should be followed by a meal within approximately 30 minutes of administration The average range of total daily insulin requirement for maintenance therapy in insulin-treated patients lies between 0.5 and 1.0 IU/kg. | During episodes of hypoglycemia and in patients with hypersensitivity to Novolin R | Hypoglycemia, or low blood sugar, is the most common side effect. Symptoms include headache, hunger, dizziness, sweating, irritability, trouble concentrating, rapid breathing, fast heartbeat, fainting, or seizure (severe hypoglycemia can be fatal). | Link | NA | NA |
| 10209 | Th1027 | Insulin Regular | >Th1027_Insulin_Regular GIVEQCCTSICSLYQLENYCN | 5808 | C257H383N65O77S6 | 5.39 | 0.218 | 81 | 2-3.4 hours | Insulin regular is a 51 residue peptide hormone, composed of two amino acid chains covalently linked by disulfide bonds. The structure is identical to native human insulin. Recombinant insulin is synthesized by recombinant DNA techncology. Inserting the human insulin gene into the Escherichia coli bacteria or Saccharomyces cerevisiae produces insulin for human use. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 1 and type 2 diabetes mellitus. | Insulin regular is a short-acting insulin. When subcutaneously administered, the onset of action (as evidenced by a decrease in glucose level) occurs 30 minutes post-dose. Maximal effect occurs between 1.5 and 3.5 hours post-dose. The glucose-lowering effect occurs 8 hours post-dose. Compared to other rapid-acting insulin analogs, insulin regular has a slower onset of action and longer duration of action. | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism. | Hypoglycemia is caused due to insulin toxicity. | Predominantly cleared by metabolic degradation via a receptor-mediated process. | Generally well absorbed. | 0.15 L/kg | NA | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin, metabolism, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10275 | Th1040 | Insulin Lispro | >Th1040_Insulin_Lispro GIVEQCCTSICSLYQLENYCN | 5808 | C257H387N65O76S6 | 5.39 | 0.218 | 81 | On subcutaneous administration = 1 hour | Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. | To treat type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. | Insulin lispro binds to the insulin receptor(IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and -cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweat | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. | Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. Aft | When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively). | Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively. | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin Analog, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | US5474978 | 12-Dec-1995 | 16-Jun-2014 | The beta-blocker, acebutolol, atenolol, bisoprolol, carvedilol, may decrease symptoms of hypoglycemia. | Insulin receptor,Insulin-like growth factor 1 receptor | Humalog | Eli Lilly | Eli Lilly | Humalog is used to treat type 1 diabetes in adults. It is usually given together with another long-acting insulin. Humalog is also used together with oral medications to treat type 2 diabetes in adults. | NA | Each milliliter of HUMALOG contains insulin lispro 100 units, 16 mg glycerin, 1.88 mg dibasic sodium phosphate, 3.15 mg Metacresol, zinc oxide content adjusted to provide 0.0197 mg zinc ion, trace amounts of phenol, and Water for Injection. Insulin lispro | Sterile, aqueous, clear, and colorless solution | Subcutaneous and Intravenous infusion | The total daily insulin requirement may vary and is usually between 0.5 to 1 unit/kg/day. Insulin requirements may be altered during stress, major illness, or with changes in exercise, meal patterns, or coadministered drugs. Usual maintenance range is 0.5-1 unit/kg/day in divided doses; nonobese may require 0.4-0.6 unit/kg/day; obese may require 0.8-1.2 units/kg/day. | During episodes of hypoglycemia in patients who are hypersensitive to HUMALOG or to any of its excipients. | Low blood sugar--headache, hunger, weakness, sweating, confusion, irritability, dizziness, fast heart rate, or feeling jittery. | Link | NA | NA |
| 10276 | Th1040 | Insulin Lispro | >Th1040_Insulin_Lispro GIVEQCCTSICSLYQLENYCN | 5808 | C257H387N65O76S6 | 5.39 | 0.218 | 81 | On subcutaneous administration = 1 hour | Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. | To treat type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. | Insulin lispro binds to the insulin receptor(IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and -cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweat | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. | Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. Aft | When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively). | Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively. | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin Analog, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | US5514646 | 7-May-1996 | 7-May-2013 | Concomitant therapy with drugs like Dextropropoxyphene, Pentoxifylline, Pramlintide, Fluoxetine, Fenofibrate and Disopyramide that may increase the blood-glucose-lowering effect of insulin lispro | NA | Admelog | Sanofi Aventis, REMEDYREPACK INC. | Sanofi Aventis, REMEDYREPACK INC. | symptoms of Type 1 or 2 Diabetes Mellitus. | C257H383N65O77S6 | Insulin lispro is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli. Insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. | sterile, aqueous, clear, and colorless solution. | Subcutaneous Injection | Dilute ADMELOG to concentrations from 0.1 unit/mL to 1 unit/mL using 0.9% sodium chloride. Administer ADMELOG intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia | ADMELOG is contraindicated: during episodes of hypoglycemia. in patients who are hypersensitive to insulin lispro or to any of the excipients. Clinical Pharmacology | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, redness or swelling where an injection was given, itchy skin rash over the entire body, fast heartbeats, lightheadedness, weight gain, swelling in your hands or feet, shortness of breath, headache, hunger, sweating, irritability, dizziness, anxiety, shakiness, leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness, and limp feeling | Link | NA | NA |
| 10277 | Th1040 | Insulin Lispro | >Th1040_Insulin_Lispro GIVEQCCTSICSLYQLENYCN | 5808 | C257H387N65O76S6 | 5.39 | 0.218 | 81 | On subcutaneous administration = 1 hour | Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. | To treat type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. | Insulin lispro binds to the insulin receptor(IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and -cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweat | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. | Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. Aft | When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively). | Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively. | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin Analog, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | CA2151564 | 11-Feb-2003 | 12-Jun-2015 | Concomitant therapy with ACE inhibitors like Enalapril and Ramipril may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely. | NA | Insulin Lispro | A-S Medication Solutions, Eli Lilly and Company, REMEDYREPACK INC., ImClone LLC | A-S Medication Solutions, Eli Lilly and Company, REMEDYREPACK INC., ImClone LLC | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10278 | Th1040 | Insulin Lispro | >Th1040_Insulin_Lispro GIVEQCCTSICSLYQLENYCN | 5808 | C257H387N65O76S6 | 5.39 | 0.218 | 81 | On subcutaneous administration = 1 hour | Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. | To treat type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. | Insulin lispro binds to the insulin receptor(IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and -cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweat | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. | Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. Aft | When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively). | Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively. | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin Analog, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | CA2151560 | 9-May-2000 | 12-Jun-2015 | Concomitant therapy with diuretics like Hydrochlorothiazide may reduce the blood-glucose-lowering effect of insulin lispro. | NA | Humalog KwikPen | Eli Lilly | Eli Lilly | Insulin lispro is used to treat type 1 diabetes in adults. It is usually given together with another long-acting insulin. Insulin lispro is also used together with oral medication to treat type 2 diabetes in adults. | NA | NA | Solution | Subcutaneous injection | Insulin lispro can be administered intravenously under medical supervision at concentrations from 0.1 unit/mL to 1 unit/mL in infusion systems containing 0.9% sodium chloride. Blood glucose and potassium levels should be closely monitored to avoid hypoglycemia. | During episodes of hypoglycemia in patients who are hypersensitive to HUMALOG or to any of its excipients. | Low blood sugar is the most common side effect. There are many causes of low blood sugar, including taking too much Humalog. Severe life-threatening allergic reactions (whole-body reactions) can happen.Reactions at the injection site (local allergic reaction. | Link | NA | NA |
| 10279 | Th1040 | Insulin Lispro | >Th1040_Insulin_Lispro GIVEQCCTSICSLYQLENYCN | 5808 | C257H387N65O76S6 | 5.39 | 0.218 | 81 | On subcutaneous administration = 1 hour | Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. | To treat type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. | Insulin lispro binds to the insulin receptor(IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and -cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweat | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. | Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. Aft | When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively). | Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively. | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin Analog, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | Concomitant therapy with angiotensin II receptor blockers like Losartan may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely. | NA | Liprelog | Eli Lilly & Co. Ltd. | Eli Lilly & Co. Ltd. | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10280 | Th1040 | Insulin Lispro | >Th1040_Insulin_Lispro GIVEQCCTSICSLYQLENYCN | 5808 | C257H387N65O76S6 | 5.39 | 0.218 | 81 | On subcutaneous administration = 1 hour | Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. | To treat type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. | Insulin lispro binds to the insulin receptor(IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and -cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweat | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. | Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. Aft | When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively). | Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively. | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin Analog, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | Concomitant therapy with somatostatin analogs like Octreotide may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely. | NA | Humalog Pen | Eli Lilly | Eli Lilly | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10281 | Th1040 | Insulin Lispro | >Th1040_Insulin_Lispro GIVEQCCTSICSLYQLENYCN | 5808 | C257H387N65O76S6 | 5.39 | 0.218 | 81 | On subcutaneous administration = 1 hour | Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. | To treat type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. | Insulin lispro binds to the insulin receptor(IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and -cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweat | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. | Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. Aft | When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively). | Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively. | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin Analog, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | The beta-blocker, esmolol, may decrease symptoms of hypoglycemia. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10282 | Th1040 | Insulin Lispro | >Th1040_Insulin_Lispro GIVEQCCTSICSLYQLENYCN | 5808 | C257H387N65O76S6 | 5.39 | 0.218 | 81 | On subcutaneous administration = 1 hour | Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. | To treat type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis. | Insulin lispro binds to the insulin receptor(IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and -cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweat | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. | Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. Aft | When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively). | Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively. | Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Blood Glucose Lowering Agents, Cytochrome P-450 CYP1A2 Inducers, Cytochrome P-450 CYP1A2 Inducers (strength unknown), Cytochrome P-450 Enzyme Inducers, Drugs Used in Diabetes, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Hypoglycemia-Associated Agents, Insulin, Insulin Analog, Insulin, Short-Acting, Insulins and Analogues for Injection, Fast-Acting, Pancreatic Hormones, Peptide Hormones, Peptides | NA | NA | NA | Concomitant therapy with sympathomimetic agents like Epinephrine may reduce the blood-glucose-lowering effect of insulin lispro. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 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 (αvβ3) 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 αvβ3 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 (αvβ3) 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 αvβ3 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 (αvβ3) 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 αvβ3 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 (αvβ3) 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 αvβ3 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 |
| 10368 | Th1054 | Infliximab | NA | 144190.3 | C6428H9912N1694O1987S46 | 8.25 | -0.441 | 71 | 9.5 days | Tumor necrosis factor (TNF-alpha) binding antibody (chimeric IgG1). It is composed of human constant and murine variable regions. Infliximab is produced by a recombinant cell line cultured by continuous perfusion. | To manage the signs and symptoms, as well as to induce and maintain clinical remission in adults with moderate to severe active Crohn's disease or ulcerative colitis. Also used to manage signs and symptoms of rheumatoid arthritis (in conjunction with methotrexate), ankylosing spondylitis, psoriatic arthritis, and juvenile arthritis. | Infliximab is a chimeric human-murine anti-human tumor necrosis factor (TNF) monoclonal antibody. It binds to tumor necrosis factor alpha (TNFa) and inhibits binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as interleukins (IL) 1 and 6. This also limits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Infliximab decreases synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal. | Infliximab neutralizes the biological activity of TNFa by binding with high affinity to the soluble and transmembrane forms of TNFa and inhibits binding of TNFa with its receptors. Infliximab does not neutralize TNFb (lymphotoxin a), a related cytokine that utilizes the same receptors as TNFa. Neutralization of the biological activity of TNFa leads to an overall reduction in inflammation. | NA | Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production | NA | NA | In patients with Crohn's disease, the total body clearance (CL) of infliximab following single doses of 5 mg/kg and 10 mg/kg was 18.4 mL/h and 14.3 mL/h, respectively. In a maintenance therapy study, multiple infusions of infliximab (at week 0, 2 and 6) at the same dose of 5 mg/kg and 10 mg/kg resulted in CL of 15.2 mL/h and 15.2 mL/h, respectively. | Agents Causing Muscle Toxicity, Agents reducing cytokine levels, Amino Acids, Peptides, and Proteins, Anti-Inflammatory Agents, Antibodies, Antibodies, Monoclonal, Antineoplastic and Immunomodulating Agents, Antirheumatic Agents, Biological Products, Biologics for Rheumatoid Arthritis Treatment, Blood Proteins, Complex Mixtures, Dermatologicals, Disease-modifying Antirheumatic Agents, Gastrointestinal Agents, Globulins, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Proteins, Serum Globulins, Tumor Necrosis Factor Blockers, Tumor Necrosis Factor Receptor Blocking Activity | CA2106299 | 6-Feb-2001 | 18-Mar-2012 | Golimumab avoid combination with infliximab due to the potential increased immunosuppression of infliximab | Tumor necrosis factor | REMICADE | Centocor Inc | Centocor Inc | used in crohn disease, Ankylosing pondylitis, Psoriatic Arthritis, Plaque Psoriasis and ulcerative colitis | NA | Each single-use vial contains 100 mg infliximab, 500 mg sucrose, 0.5 mg polysorbate 80, 2.2 mg monobasic sodium phosphate, monohydrate, and 6.1 mg dibasic sodium phosphate, dihydrate. No preservatives are present. | REMICADE is supplied as a Sterile, white, lyophilized powder, Following reconstitution with 10 mL of Sterile Water for Injection, USP, the resulting pH is approximately 7.2. | Intravenous infusion | for crohn disease, Ankylosing pondylitis, Psoriatic Arthritis, Plaque Psoriasis and ulcerative colitis : The recommended dose of REMICADE is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks for rhematoid arthritis: The recommended dose of REMICADE is 3 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks | REMICADE at doses > 5 mg/kg should not be administered to patients with moderate to severe heart failure.; REMICADE should not be re-administered to patients who have experienced a severe hypersensitivity reaction to REMICADE | Hepatotoxicity, Immunogenicity, Nausea, Diarrhea, Dysepsia, Sinusitis, Bronchitis, Phrayngitis, Rash, Fatigue, Fever, urinary tract infections. | Link | NA | NA |
| 10369 | Th1054 | Infliximab | NA | 144190.3 | C6428H9912N1694O1987S46 | 8.25 | -0.441 | 71 | 9.5 days | Tumor necrosis factor (TNF-alpha) binding antibody (chimeric IgG1). It is composed of human constant and murine variable regions. Infliximab is produced by a recombinant cell line cultured by continuous perfusion. | To manage the signs and symptoms, as well as to induce and maintain clinical remission in adults with moderate to severe active Crohn's disease or ulcerative colitis. Also used to manage signs and symptoms of rheumatoid arthritis (in conjunction with methotrexate), ankylosing spondylitis, psoriatic arthritis, and juvenile arthritis. | Infliximab is a chimeric human-murine anti-human tumor necrosis factor (TNF) monoclonal antibody. It binds to tumor necrosis factor alpha (TNFa) and inhibits binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as interleukins (IL) 1 and 6. This also limits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Infliximab decreases synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal. | Infliximab neutralizes the biological activity of TNFa by binding with high affinity to the soluble and transmembrane forms of TNFa and inhibits binding of TNFa with its receptors. Infliximab does not neutralize TNFb (lymphotoxin a), a related cytokine that utilizes the same receptors as TNFa. Neutralization of the biological activity of TNFa leads to an overall reduction in inflammation. | NA | Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production | NA | NA | In patients with rheumatoid arthritis, the CL of infliximab following a single dose infusion of 5 mg/kg, 10 mg/kg and 20 mg/kg were 11±7.5 mL/h, 11.4±5 mL/h, and 11±8.9 mL/h, respectively. | Agents Causing Muscle Toxicity, Agents reducing cytokine levels, Amino Acids, Peptides, and Proteins, Anti-Inflammatory Agents, Antibodies, Antibodies, Monoclonal, Antineoplastic and Immunomodulating Agents, Antirheumatic Agents, Biological Products, Biologics for Rheumatoid Arthritis Treatment, Blood Proteins, Complex Mixtures, Dermatologicals, Disease-modifying Antirheumatic Agents, Gastrointestinal Agents, Globulins, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Proteins, Serum Globulins, Tumor Necrosis Factor Blockers, Tumor Necrosis Factor Receptor Blocking Activity | NA | NA | NA | Rilonacept results in increased immunosuppressive effects; increases the risk of infection | NA | Avsola | AMGEN INC | AMGEN INC | Rheumatoid Arthritis -adults with moderately to severely active rheumatoid arthritis, along with the medicine methotrexate. Crohn's Disease -children 6 years and older and adults with Crohn's disease who have not responded well to other medicines. Ankylosing Spondylitis. Psoriatic Arthritis. Plaque Psoriasis -adult patients with plaque psoriasis that is chronic (does not go away), severe, extensive, and/or disabling. Ulcerative Colitis -children 6 years and older and adults with moderately to severely active ulcerative colitis who have not responded well to other medicines. | NA | Following reconstitution with 10 mL of Sterile Water for Injection, USP, the resulting pH is approximately 7.2. Each single-dose vial contains 100 mg infliximab-axxq, dibasic sodium phosphate, anhydrous (4.9 mg), monobasic sodium phosphate, monohydrate (2.2 mg), polysorbate 80 (0.5 mg), and sucrose (500 mg). | sterile, white to slightly yellow, lyophilized powder | intravenous infusion. | Crohn's Disease The recommended dose of AVSOLA is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn's disease or fistulizing Crohn's disease. For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg. Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue AVSOLA in these patients. Pediatric Crohn's Disease The recommended dose of AVSOLA for pediatric patients 6 years and older with moderately to severely active Crohn's disease is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks. Ulcerative Colitis The recommended dose of AVSOLA is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adult patients with moderately to severely active ulcerative colitis. Pediatric Ulcerative Colitis The recommended dose of AVSOLA for pediatric patients 6 years and older with moderately to severely active ulcerative colitis is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks. Rheumatoid Arthritis The recommended dose of AVSOLA is 3 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 3 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active rheumatoid arthritis. AVSOLA should be given in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dose up to 10 mg/kg or treating as often as every 4 weeks bearing in mind that risk of serious infections is increased at higher doses [see ADVERSE REACTIONS]. Ankylosing Spondylitis The recommended dose of AVSOLA is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 6 weeks thereafter for the treatment of active ankylosing spondylitis. Psoriatic Arthritis The recommended dose of AVSOLA is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of psoriatic arthritis. AVSOLA can be used with or without methotrexate. Plaque Psoriasis The recommended dose of AVSOLA is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of chronic severe (i.e., extensive and/or disabling) plaque psoriasis. | AVSOLA at doses >5 mg/kg should not be administered to patients with moderate to severe heart failure. In a randomized study evaluating infliximab in patients with moderate to severe heart failure (New York Heart Association [NYHA] Functional Class III/IV), infliximab treatment at 10 mg/kg was associated with an increased incidence of death and hospitalization due to worsening heart failure. AVSOLA should not be re-administered to patients who have experienced a severe hypersensitivity reaction to infliximab products. Additionally, AVSOLA should not be administered to patients with known hypersensitivity to inactive components of the product or to any murine proteins. | feel unwell tiredness (fatigue) poor appetite fever, skin rash, or joint pain | Link | NA | NA |
| 10370 | Th1054 | Infliximab | NA | 144190.3 | C6428H9912N1694O1987S46 | 8.25 | -0.441 | 71 | 9.5 days | Tumor necrosis factor (TNF-alpha) binding antibody (chimeric IgG1). It is composed of human constant and murine variable regions. Infliximab is produced by a recombinant cell line cultured by continuous perfusion. | To manage the signs and symptoms, as well as to induce and maintain clinical remission in adults with moderate to severe active Crohn's disease or ulcerative colitis. Also used to manage signs and symptoms of rheumatoid arthritis (in conjunction with methotrexate), ankylosing spondylitis, psoriatic arthritis, and juvenile arthritis. | Infliximab is a chimeric human-murine anti-human tumor necrosis factor (TNF) monoclonal antibody. It binds to tumor necrosis factor alpha (TNFa) and inhibits binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as interleukins (IL) 1 and 6. This also limits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Infliximab decreases synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal. | Infliximab neutralizes the biological activity of TNFa by binding with high affinity to the soluble and transmembrane forms of TNFa and inhibits binding of TNFa with its receptors. Infliximab does not neutralize TNFb (lymphotoxin a), a related cytokine that utilizes the same receptors as TNFa. Neutralization of the biological activity of TNFa leads to an overall reduction in inflammation. | NA | Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production | NA | NA | NA | Agents Causing Muscle Toxicity, Agents reducing cytokine levels, Amino Acids, Peptides, and Proteins, Anti-Inflammatory Agents, Antibodies, Antibodies, Monoclonal, Antineoplastic and Immunomodulating Agents, Antirheumatic Agents, Biological Products, Biologics for Rheumatoid Arthritis Treatment, Blood Proteins, Complex Mixtures, Dermatologicals, Disease-modifying Antirheumatic Agents, Gastrointestinal Agents, Globulins, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Proteins, Serum Globulins, Tumor Necrosis Factor Blockers, Tumor Necrosis Factor Receptor Blocking Activity | NA | NA | NA | Tofacitinib avoid combination with infliximab and other anti-TNF drugs due to the potential enhancement of tofacitinib related adverse effects | NA | Flixabi | Samsung Bioepis Nl B.V. | Samsung Bioepis Nl B.V. | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10371 | Th1054 | Infliximab | NA | 144190.3 | C6428H9912N1694O1987S46 | 8.25 | -0.441 | 71 | 9.5 days | Tumor necrosis factor (TNF-alpha) binding antibody (chimeric IgG1). It is composed of human constant and murine variable regions. Infliximab is produced by a recombinant cell line cultured by continuous perfusion. | To manage the signs and symptoms, as well as to induce and maintain clinical remission in adults with moderate to severe active Crohn's disease or ulcerative colitis. Also used to manage signs and symptoms of rheumatoid arthritis (in conjunction with methotrexate), ankylosing spondylitis, psoriatic arthritis, and juvenile arthritis. | Infliximab is a chimeric human-murine anti-human tumor necrosis factor (TNF) monoclonal antibody. It binds to tumor necrosis factor alpha (TNFa) and inhibits binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as interleukins (IL) 1 and 6. This also limits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Infliximab decreases synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal. | Infliximab neutralizes the biological activity of TNFa by binding with high affinity to the soluble and transmembrane forms of TNFa and inhibits binding of TNFa with its receptors. Infliximab does not neutralize TNFb (lymphotoxin a), a related cytokine that utilizes the same receptors as TNFa. Neutralization of the biological activity of TNFa leads to an overall reduction in inflammation. | NA | Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production | NA | NA | NA | Agents Causing Muscle Toxicity, Agents reducing cytokine levels, Amino Acids, Peptides, and Proteins, Anti-Inflammatory Agents, Antibodies, Antibodies, Monoclonal, Antineoplastic and Immunomodulating Agents, Antirheumatic Agents, Biological Products, Biologics for Rheumatoid Arthritis Treatment, Blood Proteins, Complex Mixtures, Dermatologicals, Disease-modifying Antirheumatic Agents, Gastrointestinal Agents, Globulins, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Proteins, Serum Globulins, Tumor Necrosis Factor Blockers, Tumor Necrosis Factor Receptor Blocking Activity | NA | NA | NA | Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events | NA | Inflectra | Pfizer Europe Ma Eeig | Pfizer Europe Ma Eeig | Crohn's Disease | NA | Following reconstitution with 10 mL of Sterile Water for Injection, USP, the resulting pH is approximately 7.2. Each single-use vial contains 100 mg infliximab-dyyb, 500 mg sucrose, 0.5 mg polysorbate 80, 2.2 mg sodium dihydrogen phosphate monohydrate, and 6.1 mg di-Sodium hydrogen phosphate dihydrate. No preservatives are present. | sterile, white, lyophilized powder | intravenous Injection | The recommended dose of INFLECTRA is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn's disease or fistulizing Crohn's disease. For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg. Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue INFLECTRA in these patients. | INFLECTRA at doses >5 mg/kg should not be administered to patients with moderate to severe heart failure. In a randomized study evaluating infliximab in patients with moderate to severe heart failure (New York Heart Association [NYHA] Functional Class III/IV), infliximab treatment at 10 mg/kg was associated with an increased incidence of death and hospitalization due to worsening heart failure. INFLECTRA should not be readministered to patients who have experienced a severe hypersensitivity reaction to infliximab products. Additionally, INFLECTRA should not be administered to patients with known hypersensitivity to inactive components of the product or to any murine proteins. | upper respiratory infections sinus infections runny or stuffy nose sore throat cough bronchitis infusion-related reactions headache abdominal pain nausea diarrhea indigestion rash itching fatigue pain fever oral thrush joint pain urinary tract infection, and high blood pressure (hypertension) | Link | NA | NA |
| 10505 | Th1098 | Exenatide | >Th1098_Exenatide HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS | 4186.6 | C184H282N50O60S | 4.86 | NA | NA | Mean terminal half-life is 2.4 hours. | Derived from a compound found in the saliva of the Gila monster, a large lizard native to the southwestern United States. It is a functional analog of Glucagon-Like Peptide-1 (GLP-1) peptide. | Indicated as adjunctive therapy to improve glycemic control in patients with Type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of both, but have not achieved adequate glycemic control. | Exenatide is an incretin mimetic, which has glucoregulatory effects. While it is has blood-sugar lowering actions alone, it can also be combined with other medications such as pioglitazone, metformin, sulfonylureas, and/or insulin to improve glucose control. The approved use of exenatide is with either sulfonylureas, metformin and thiazolinediones. The medication is injected twice per day using a pre-filled pen device. Typical human responses to exenatide plus eating include improvements in the initial rapid release of endogenous insulin, suppression of glucagon release by the pancreas, regulation of gastric empyting and reduced appetite; all behaviors more typical of individuals without blood sugar control problems. Exenatide is self-regulating in that in lowers blood sugar when levels are elevated but does not continue to lower blood sugar when levels return to normal, unlike with sulfonylureas or insulins. | Exenatide is a functional analog of the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meals. | In animal studies, exenatide was associated with fetal deformities of ribs and vertebrae as well as slowed growthLabel. In humans, uncontrolled hyperglycemia can be associated with an up to 25% risk of miscarriageLabel. No human studies in pregnancy have been performed with exenatide and so exenatide should only be prescribed in pregnancy if the benefit to the mother and fetus outweigh the risksLabel. In mice, exenatide is excreted in the milk at a concentration 2.5% of the plasma concentration though this data may not be applicable to humansLabel. The effect of exenatide on breastfed infants is also unknown and so the risk and benefit of breastfeeding while taking exenatide must be weighedLabel. There is no data for the use of exenatide in pediatric patientsLabel. Geriatric patients do not have different results for safety and efficacy of exenatide though caution should still be used in this group as they are at higher risk of renal impairment or other comorbidities that may affect the liklihood of adverse effectsLabel. No dosage adjustments are necessary for patients with creatinine clearance ≥50mL/min, though prescribing to patients with creatinine clearance 30-50mL/min should be done cautiouslyLabel. Exenatide is not recommended for patients with creatinine clearance <30mL/minLabel. Hepatic impairment is not expected to affect clearance of exenatide though no studies have been performed to confirm thisLabel. | Exenatide is filtered through the glomerulus before being degraded to smaller peptides and amino acids by dipeptidyl peptidase-4, metalloproteases, endopeptidase 24-11, amino proteases, and serine proteases. It is currently believed that the metalloproteases are responsible for most of the degradation of exenatide3. Exenatide is metabolised to small peptides <3 amino acids in length by enzymes in the kidney | Exenatide reaches a peak plasma concentration in 2.1 hoursLabel. Because exenatide is administerd subcutaneously, the bioavailability is 1 | 28.3 L | Apparent cl=9.1 L/hr | Hypoglycemic Agents | US6872700 | 29-Mar-2005 | 29-Mar-2005 | NA | Glucagon-like peptide 1 receptor | BYETTA | NA | NA | BYETTA (exenatide injection) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | NA | BYETTA (exenatide injection) is supplied for SC injection as a sterile, preserved isotonic solution in a glass cartridge that has been assembled in a pen-injector (pen). Each milliliter (mL) contains 250 micrograms (mcg) synthetic exenatide, 2.2 mg metacresol as an antimicrobial preservative, mannitol as a tonicity-adjusting agent, and glacial acetic acid and sodium acetate trihydrate in water for injection as a buffering solution at pH 4.5. Two prefilled pens are available to deliver unit doses of 5 mcg or 10 mcg. Each prefilled pen will deliver 60 doses to provide for 30 days of twice daily administration (BID). | NA | NA | BYETTA (exenatide injection) should be initiated at 5 mcg administered twice daily at any time within the 60-minute period before the morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart). BYETTA (exenatide injection) should not be administered after a meal. Based on clinical response, the dose of BYETTA (exenatide injection) can be increased to 10 mcg twice daily after 1 month of therapy. Initiation with 5 mcg reduces the incidence and severity of gastrointestinal side effects. Use BYETTA (exenatide injection) only if it is clear, colorless and contains no particles. | BYETTA (exenatide injection) is not a substitute for insulin. BYETTA (exenatide injection) should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. The concurrent use of BYETTA (exenatide injection) with insulin has not been studied and cannot be recommended.Based on postmarketing data BYETTA (exenatide injection) has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. BYETTA (exenatide injection) has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYETTA (exenatide injection) . Other antidiabetic therapies should be considered in patients with a history of pancreatitis. | Severe allergic reactions include severe rash or itching, swelling of your face, lips, and throat that may cause difficulty breathing or swallowing, feeling faint or dizzy and very rapid heartbeat. Inflammation of the pancreas (pancreatitis) may happen, which may be severe and lead to death. Your risk for getting low blood sugar (hypoglycemia) is higher. Signs and symptoms of low blood sugar may include headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, sweating, and feeling jittery. | NA | NA | NA |
| 10506 | Th1098 | Exenatide | >Th1098_Exenatide HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS | 4186.6 | C184H282N50O60S | 4.86 | NA | NA | Mean terminal half-life is 2.4 hours. | Derived from a compound found in the saliva of the Gila monster, a large lizard native to the southwestern United States. It is a functional analog of Glucagon-Like Peptide-1 (GLP-1) peptide. | Indicated as adjunctive therapy to improve glycemic control in patients with Type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of both, but have not achieved adequate glycemic control. | Exenatide is an incretin mimetic, which has glucoregulatory effects. While it is has blood-sugar lowering actions alone, it can also be combined with other medications such as pioglitazone, metformin, sulfonylureas, and/or insulin to improve glucose control. The approved use of exenatide is with either sulfonylureas, metformin and thiazolinediones. The medication is injected twice per day using a pre-filled pen device. Typical human responses to exenatide plus eating include improvements in the initial rapid release of endogenous insulin, suppression of glucagon release by the pancreas, regulation of gastric empyting and reduced appetite; all behaviors more typical of individuals without blood sugar control problems. Exenatide is self-regulating in that in lowers blood sugar when levels are elevated but does not continue to lower blood sugar when levels return to normal, unlike with sulfonylureas or insulins. | Exenatide is a functional analog of the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meals. | In animal studies, exenatide was associated with fetal deformities of ribs and vertebrae as well as slowed growthLabel. In humans, uncontrolled hyperglycemia can be associated with an up to 25% risk of miscarriageLabel. No human studies in pregnancy have been performed with exenatide and so exenatide should only be prescribed in pregnancy if the benefit to the mother and fetus outweigh the risksLabel. In mice, exenatide is excreted in the milk at a concentration 2.5% of the plasma concentration though this data may not be applicable to humansLabel. The effect of exenatide on breastfed infants is also unknown and so the risk and benefit of breastfeeding while taking exenatide must be weighedLabel. There is no data for the use of exenatide in pediatric patientsLabel. Geriatric patients do not have different results for safety and efficacy of exenatide though caution should still be used in this group as they are at higher risk of renal impairment or other comorbidities that may affect the liklihood of adverse effectsLabel. No dosage adjustments are necessary for patients with creatinine clearance ≥50mL/min, though prescribing to patients with creatinine clearance 30-50mL/min should be done cautiouslyLabel. Exenatide is not recommended for patients with creatinine clearance <30mL/minLabel. Hepatic impairment is not expected to affect clearance of exenatide though no studies have been performed to confirm thisLabel. | Exenatide is filtered through the glomerulus before being degraded to smaller peptides and amino acids by dipeptidyl peptidase-4, metalloproteases, endopeptidase 24-11, amino proteases, and serine proteases. It is currently believed that the metalloproteases are responsible for most of the degradation of exenatide3. Exenatide is metabolised to small peptides <3 amino acids in length by enzymes in the kidney | Exenatide reaches a peak plasma concentration in 2.1 hoursLabel. Because exenatide is administerd subcutaneously, the bioavailability is 1 | 28.3 L | Apparent cl=9.1 L/hr | Hypoglycemic Agents | US5424286 | 13-Jun-1995 | 1-Dec-2016 | NA | Glucagon-like peptide 1 receptor | BYDUREON | Amylin Pharmaceuticals | Amylin Pharmaceuticals | BYDUREON is an extended-release formulation of exenatide, administered as an injection once every 7 days (weekly). BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus | NA | Exenatide is incorporated in an extended-release microsphere formulation containing the 50:50 poly(D,L-lactide-co-glycolide) polymer (37.2 mg per dose) along with sucrose (0.8 mg per dose). The powder must be suspended in the diluent prior to injection. The diluent for the BYDUREON vial is supplied in a prefilled syringe within each single-dose tray. The diluent for the BYDUREON Pen is contained within each single-dose pen. Each configuration contains sufficient diluent to deliver 0.65 mL. The diluent is a clear, colorless to pale-yellow solution composed of carboxymethylcellulose sodium (19 mg), polysorbate 20 (0.63 mg), sodium phosphate monobasic monohydrate (0.61 mg), sodium phosphate dibasic heptahydrate (0.51 mg), sodium chloride (4.1 mg), and water for injection. Sodium hydroxide may be added during manufacture of BYDUREON Pen for pH adjustment. | White to off-white powder that is available in a dosage strength of 2 mg exenatide per vial or per pen | NA | BYDUREON (2 mg per dose) should be administered once every 7 days (weekly). The dose can be administered at any time of day, with or without meals. | BYDUREON is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise. BYDUREON is not a substitute for insulin. BYDUREON should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. BYDUREON and BYETTA (exenatide) injection both contain the same active ingredient, exenatide, and therefore should not be used together. BYDUREON has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYDUREON. Other antidiabetic therapies should be considered in patients with a history of pancreatitis. | Possible thyroid tumors, including cancer, Allergic reaction Pancreatitis, Hypoglycemia | Link | NA | NA |
| 10509 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S2 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | US5686411 | 11-Nov-1997 | 16-Mar-2019 | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | Symlin | Amylin Pharmaceuticals (now a wholly owned subsidiary of AstraZeneca) | Amylin Pharmaceuticals (now a wholly owned subsidiary of AstraZeneca) | SYMLIN is indicated as an adjunctive treatment in patients with type 1 or type 2 diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy. | NA | The disposable multidose SymlinPen pen-injector contains 1000 mcg/mL of pramlintide (as acetate). The formulation contains 2.25 mg/mL of metacresol as a preservative, D-mannitol as a tonicity modifier, acetic acid, sodium acetate as pH modifiers, and water for injection. SYMLIN has a pH of approximately 4.0 | Clear, isotonic, sterile solution for subcutaneous administration | Subcutaneous | Reduce mealtime insulin doses by 50%, then initiate SYMLIN at 15 mcg subcutaneously, injecting immediately prior to each major meal. Increase the SYMLIN dose to the next increment (30, 45, or 60 mcg) when no clinically significant nausea has occurred for at least 3 days. If significant nausea persists at the 45 or 60 mcg dose level, the SYMLIN dose should be decreased to 30 mcg. If the 30 mcg dose is not tolerated, discontinuation of SYMLIN therapy should be considered. | NA | Nausea, Anorexia, Vomiting, Arthralgia, Fatigue, Allergic Reaction, Dizziness | Link | NA | NA |
| 10510 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S3 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | US6610824 | 26-Aug-2003 | 29-May-2011 | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10511 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S4 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10512 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S5 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10513 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S6 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10514 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S7 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10515 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S8 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10516 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S9 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10517 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S10 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10518 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S11 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10519 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S12 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10520 | Th1100 | Pramlintide | >Th1100_Pramlintide KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY | 3949.44 | C171H267N51O53S13 | NA | NA | NA | Approximately 48 minutes | New adjunct treatment for type I and type II diabetes. It is developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone released after meal, in a pattern similar to insulin. Diabetic patients are also deficient in amylin. | For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy. | Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. | Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | NA | Metabolized primarily by the kidneys. | The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%. | NA | NA | NA | NA | NA | NA | NA | Calcitonin receptor,Receptor activity-modifying protein 1,Receptor activity-modifying protein 2,Receptor activity-modifying protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10529 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | US5866538 | 2-Feb-1999 | 20-Jun-2017 | NA | Insulin receptor,Insulin-like growth factor 1 receptor | NovoLog | Novo Nordisk | Novo Nordisk | NovoLog is an insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus | NA | NovoLog is a sterile, aqueous, clear, and colorless solution, that contains insulin aspart 100 Units/mL, glycerin 16 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 19.6 mcg/mL, disodium hydrogen phosphate dihydrate 1.25 mg/mL, sodium chloride 0.58 mg/mL and water for injection. NovoLog has a pH of 7.2-7.6. Hydrochloric acid 10% and/or sodium hydroxide 10% may be added to adjust pH | Sterile, aqueous, clear, and colorless solution | Subcutaneous, Intravenous | The total daily insulin requirement may vary and is usually between 0.5 to 1.0 units/kg/day. When used in a meal-related subcutaneous injection treatment regimen, 50 to 70% of total insulin requirements may be provided by NovoLog and the remainder provided by an intermediate-acting or long-acting insulin. Because of NovoLog's comparatively rapid onset and short duration of glucose lowering activity, some patients may require more basal insulin and more total insulin to prevent pre-meal hyperglycemia when using NovoLog than when using human regular insulin. | NovoLog is contraindicated during episodes of hypoglycemia in patients with hypersensitivity to NovoLog or one of its excipients | swelling in your hands or feet; or low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling). Hypoglycemia, Lipodystrophy, Weight gain, Peripheral Edema | Link | NA | NA |
| 10530 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | US5618913 | 8-Apr-1997 | 7-Jun-2014 | NA | Insulin receptor,Insulin-like growth factor 1 receptor | NovoLog Mix 50/50 | Novo Nordisk | Novo Nordisk | NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is indicated as an adjunct to diet and exercise to improve glycemic control in patients with diabetes mellitus. | NA | NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is a uniform, white, sterile suspension that contains insulin aspart (B28 asp regular human insulin analog) 100 Units/ml, 16 mg glycerol, 1.50 mg phenol, 1.72 mg metacreÂÂsol, 19.6 μg zinc, 1.25 mg disodium hydrogen phosphate dihydrate, 1.17 mg sodium chloride, and 0.23 mg protamine sulfate. NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has a pH of 7.10 - 7.44. Hydrochloric acid or sodium hydroxide may be added to adjust pH | Uniform, white, sterile suspension that contains insulin aspart (B28 asp regular human insulin analog) | Subcutaneous | NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should be administered within 15 minutes of meal initiation up to three times daily. It is intended only for subcutaneous injection into the abdominal wall, thigh, or upper arm. NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should not be administered intravenously. | NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) or any of the excipients. | During clinical trials the overall adverse event profile of NovoLog Mix 50/50 was comparable to Novolin 70/30. Adverse events commonly associated with human insulin therapy include the following: Body as whole: allergic reactions, Skin and Appendages: Injection site reaction, lipodystrophy, pruritus, rash, Hypoglycemia | Link | NA | NA |
| 10531 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | NA | NA | NA | NA | Insulin receptor,Insulin-like growth factor 1 receptor | NovoLog Mix 70/30 | Novo Nordisk | Novo Nordisk | NovoLog Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart injection) is indicated as an adjunct to diet and exercise to improve glycemic control in patients with diabetes mellitus. | NA | Inactive ingredients for the 10 mL vial are mannitol 36.4 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 19.6 μg/mL, disodium hydrogen phosphate dihydrate 1.25 mg/mL, sodium chloride 0.58 mg/mL, and protamine sulfate 0.32 mg/mL. Inactive ingredients for the NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart rdna origin) FlexPen are glycerol 16.0 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 19.6 μg/mL, disodium hydrogen phosphate dihydrate 1.25 mg/mL, sodium chloride 0.877 mg/mL, and protamine sulfate 0.32 mg/mL. NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart rdna origin) has a pH of 7.20 - 7.44. Hydrochloric acid or sodium hydroxide may be added to adjust pH. | NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart rdna origin) is a uniform, white, sterile suspension that contains insulin aspart 100 Units/mL. | Subcutaneous | NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart (rdna origin)) is an insulin analog with an earlier onset and intermediate duration of action in comparison to the basal human insulin premix. The addition of protamine to the rapid-acting aspart insulin analog (NovoLog) results in insulin activity that is 30% short-acting and 70% long-acting. NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart (rdna origin)) is typically dosed on a twice-daily basis (with each dose intended to cover 2 meals or a meal and a snack). The dosage of NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart (rdna origin)) must be individualized. The written prescription for NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart (rdna origin)) should include the full name, to avoid confusion with NovoLog (insulin aspart) and Novolin 70/30 (human premix). | NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart (rdna origin)) is contraindicated during episodes of hypoglycemia in patients with hypersensitivity to NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart (rdna origin)) or one of its excipients. | signs of insulin allergy: itching skin rash over the entire body, wheezing, trouble breathing, fast heart rate, sweating, or feeling like you might pass out. Hypoglycemia, or low blood sugar, is the most common side effect of insulin. Symptoms include headache, hunger, weakness, sweating, tremors, irritability, trouble concentrating, rapid breathing, fast heartbeat, fainting, or seizure (severe hypoglycemia can be fatal) | Link | NA | NA |
| 10532 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | NA | NA | NA | NA | Insulin receptor,Insulin-like growth factor 1 receptor | Fiasp | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10533 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | NA | NA | NA | NA | Insulin receptor,Insulin-like growth factor 1 receptor | Kirsty | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10534 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | NA | NA | NA | NA | Insulin receptor,Insulin-like growth factor 1 receptor | Kixelle | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10535 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | NA | NA | NA | NA | Insulin receptor,Insulin-like growth factor 1 receptor | Novorapid | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10536 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | NA | NA | NA | NA | Insulin receptor,Insulin-like growth factor 1 receptor | Novomix 30 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10537 | Th1105 | Insulin aspart | >Th1105_Insulin_aspart GIVEQCCTSICSLYQLENYCN | 5825.8 | C256H381N65O79S6 | NA | NA | NA | 81 mins. SC injection | Recombinant (from S. cerevisiae),fast-acting insulin analogue. It contains a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This results in a decreased hexamer formation and higher rate of absorption, compared to wild type insulin, following subcutaneous administration. | For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours. | Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action. | Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. | NA | Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption. | NA | 1.2 L/h/kg [healthy Caucasian male] | Hypoglycemic Agents and Antidiabetic Agents | NA | NA | NA | NA | Insulin receptor,Insulin-like growth factor 1 receptor | Ryzodeg | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10611 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | Simponi Injection | NA | NA | Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Ulcerative Colitis | NA | pH of approximately 5.5. SIMPONI is provided in two strengths: 50 mg of the golimumab antibody in 0.5 mL of solution and 100 mg of the golimumab antibody in 1 mL of solution. In the 50 mg strength, 0.5 mL of SIMPONI contains 50 mg of the golimumab antibody, 0.44 mg of L-histidine and L-histidine monohydrochloride monohydrate, 20.5 mg of sorbitol, 0.08 mg of polysorbate 80, and Water for Injection. In the 100 mg strength, 1 mL of SIMPONI contains 100 mg of the golimumab antibody, 0.87 mg of L-histidine and L-histidine monohydrochloride monohydrate, 41.0 mg of sorbitol, 0.15 mg of polysorbate 80, and Water for Injection. | The solution is clear to slightly opalescent, colorless to light yellow | Subcutaneous | 50 mg once a month | NA | sepsis, alanine aminotransferase, aspartate aminotransferase, tuberculosis, anemia | Link | NA | NA |
| 10612 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | Simponi Aria | NA | NA | rheumatoid arthritis. | NA | SIMPONI ARIA does not contain preservatives, natural rubber or latex. The solution is colorless to light yellow with a pH of approximately 5.5. Each 4 mL vial of SIMPONI ARIA contains 50 mg golimumab, 9.5 mM histidine, 4.5% (w/v) sorbitol, and 0.015% (w/v) polysorbate 80. | The SIMPONI ARIA drug product is a sterile concentrated solution of the golimumab antibody supplied in a 4 mL glass vial for Intravenous infusion. | Intravenous infusion | 2 mg per kg | NA | sepsis, pneumonia, cellulitis, abscess, opportunistic infections, tuberculosis (TB), and invasive fungal infections, Malignancies, Liver Enzyme Elevations, Autoimmune Disorders And Autoantibodies | Link | NA | NA |
| 10613 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10614 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10615 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10616 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10617 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10618 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10619 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10620 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10621 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10622 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10623 | Th1125 | Golimumab | NA | 146943.2 | C6530H10068N1752O2026S44 | NA | NA | NA | About 2 weeks | Human IgG1Ò› monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. | Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFαis associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. | As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. | The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed. | The metabolism of golimumab has yet to be determined. | After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 µg/mL. | After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. | After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. | Antipsoriatic Agents and Monoclonal antibodies and TNF inhibitor | NA | NA | NA | NA | Tumor necrosis factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10637 | Th1132 | Belimumab | NA | 147000 | C 6358 H 9904 N 1728 O 2010 S 44 | NA | NA | NA | Elimination half life- 19.4 days, Distribution half life- 1.75 days | RAV12 is a monoclonal antibody that is being studied in the treatment of certain cancers.It binds to a carbohydrate molecule found on gastric, colon, pancreatic, prostate, ovarian, breast, and kidney cancer cells. Administering RAV12 along with gemcitabine may kill more tumor cells than either one alone. | Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus. | By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA. | Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response. | The most commonly-reported adverse reactions, occurring in =5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections. | Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes. | Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-8), 10 mg/kg, SLE patients = 3083. | Vdss, 10 mg/kg, SLE patients = 5.29 L. | Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day. | Monoclonal antibodies | NA | NA | NA | NA | Tumor necrosis factor ligand superfamily member 13B | Benlysta | GlaxoSmithKline | GlaxoSmithKline | NA | NA | Upon reconstitution with Sterile Water for Injection, USP, each single-use vial delivers 80 mg/mL belimumab in 0.16 mg/mL citric acid, 0.4 mg/mL polysorbate 80, 2.7 mg/mL sodium citrate, and 80 mg/mL sucrose, with a pH of 6.5. | BENLYSTA is supplied as a sterile, white to off-white, preservative-free, lyophilized powder for Intravenous infusion | Intravenous infusion | 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter. Reconstitute, dilute, and administer as an Intravenous infusion only, over a period of 1 hour. | anaphylaxis with belimumab | Mortality, Serious Infections, Malignancy, Hypersensitivity Reactions, Including Anaphylaxis, Infusion Reactions, Depression | Link | NA | NA |
| 10638 | Th1132 | Belimumab | NA | 147000 | C 6358 H 9904 N 1728 O 2010 S 44 | NA | NA | NA | Elimination half life- 19.4 days, Distribution half life- 1.75 days | RAV12 is a monoclonal antibody that is being studied in the treatment of certain cancers.It binds to a carbohydrate molecule found on gastric, colon, pancreatic, prostate, ovarian, breast, and kidney cancer cells. Administering RAV12 along with gemcitabine may kill more tumor cells than either one alone. | Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus. | By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA. | Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response. | The most commonly-reported adverse reactions, occurring in =5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections. | Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes. | Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-8), 10 mg/kg, SLE patients = 3083. | Vdss, 10 mg/kg, SLE patients = 5.29 L. | Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day. | Monoclonal antibodies | NA | NA | NA | NA | Tumor necrosis factor ligand superfamily member 13B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10639 | Th1132 | Belimumab | NA | 147000 | C 6358 H 9904 N 1728 O 2010 S 44 | NA | NA | NA | Elimination half life- 19.4 days, Distribution half life- 1.75 days | RAV12 is a monoclonal antibody that is being studied in the treatment of certain cancers.It binds to a carbohydrate molecule found on gastric, colon, pancreatic, prostate, ovarian, breast, and kidney cancer cells. Administering RAV12 along with gemcitabine may kill more tumor cells than either one alone. | Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus. | By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA. | Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response. | The most commonly-reported adverse reactions, occurring in =5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections. | Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes. | Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-8), 10 mg/kg, SLE patients = 3083. | Vdss, 10 mg/kg, SLE patients = 5.29 L. | Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day. | Monoclonal antibodies | NA | NA | NA | NA | Tumor necrosis factor ligand superfamily member 13B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10640 | Th1132 | Belimumab | NA | 147000 | C 6358 H 9904 N 1728 O 2010 S 44 | NA | NA | NA | Elimination half life- 19.4 days, Distribution half life- 1.75 days | RAV12 is a monoclonal antibody that is being studied in the treatment of certain cancers.It binds to a carbohydrate molecule found on gastric, colon, pancreatic, prostate, ovarian, breast, and kidney cancer cells. Administering RAV12 along with gemcitabine may kill more tumor cells than either one alone. | Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus. | By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA. | Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response. | The most commonly-reported adverse reactions, occurring in =5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections. | Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes. | Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-8), 10 mg/kg, SLE patients = 3083. | Vdss, 10 mg/kg, SLE patients = 5.29 L. | Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day. | Monoclonal antibodies | NA | NA | NA | NA | Tumor necrosis factor ligand superfamily member 13B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10641 | Th1132 | Belimumab | NA | 147000 | C 6358 H 9904 N 1728 O 2010 S 44 | NA | NA | NA | Elimination half life- 19.4 days, Distribution half life- 1.75 days | RAV12 is a monoclonal antibody that is being studied in the treatment of certain cancers.It binds to a carbohydrate molecule found on gastric, colon, pancreatic, prostate, ovarian, breast, and kidney cancer cells. Administering RAV12 along with gemcitabine may kill more tumor cells than either one alone. | Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus. | By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA. | Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response. | The most commonly-reported adverse reactions, occurring in =5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections. | Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes. | Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-8), 10 mg/kg, SLE patients = 3083. | Vdss, 10 mg/kg, SLE patients = 5.29 L. | Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day. | Monoclonal antibodies | NA | NA | NA | NA | Tumor necrosis factor ligand superfamily member 13B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10642 | Th1132 | Belimumab | NA | 147000 | C 6358 H 9904 N 1728 O 2010 S 44 | NA | NA | NA | Elimination half life- 19.4 days, Distribution half life- 1.75 days | RAV12 is a monoclonal antibody that is being studied in the treatment of certain cancers.It binds to a carbohydrate molecule found on gastric, colon, pancreatic, prostate, ovarian, breast, and kidney cancer cells. Administering RAV12 along with gemcitabine may kill more tumor cells than either one alone. | Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus. | By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA. | Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response. | The most commonly-reported adverse reactions, occurring in =5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections. | Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes. | Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-8), 10 mg/kg, SLE patients = 3083. | Vdss, 10 mg/kg, SLE patients = 5.29 L. | Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day. | Monoclonal antibodies | NA | NA | NA | NA | Tumor necrosis factor ligand superfamily member 13B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10702 | Th1161 | Albiglutide | >Th1161_Albiglutide HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRHGEGTFTSDVSSYLEGQAAKEFIAWLVKGRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL | 72970 | C3232H5032N864O979S41 | NA | NA | NA | 4-7 days. | Albiglutide is a glucagon-like peptide-1 agonist (GLP-1) biologic drug indicated in the treatment of type 2 diabetes. It is marketed under the brands Eperzan and Tanzeum by GSK (GlaxoSmithKline). It is a dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin. Albiglutide was approved on April 15, 2014 by the FDA. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | It lowers fasting glucose and reduces postprandial glucose excursions in patients with type 2 diabetes mellitus. The majority of the observed reduction in fasting plasma glucose occurs after a single dose, consistent with the pharmacokinetic profile of albiglutide. | Albiglutide is an agonist of the GLP-1 (glucagon-like peptide 1) receptor and augments glucose-dependent insulin secretion. Albiglutide also slows gastric emptying. | -RISK OF THYROID C-CELL TUMORS -Albiglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with Albiglutide. | Biotransformation studies have not been performed. Because albiglutide is an albumin fusion protein, it likely follows a metabolic pathway similar to native human serum albumin, which is catabolized primarily in the vascular endothelium. | Maximum concentrations of albiglutide were reached at 3 to 5 days post-dosing following a single 30mg dose. The mean peak concentration (Cmax) and mean area under the time-concentration curve (AUC) of albiglutide were 1.74 mcg/mL and 465 mcg.h/mL, respectively | 11 L. | 67 mL/h. | Drugs used in diabetes; alimentary tract and metabolism; blood glucose lowering drugs, excl. insulins. | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Albiglutide; Albiglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Albiglutide; Albiglutide may increase the hypoglycemic activities of Insulin Regular; Albiglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Albiglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Albiglutide; Oxandrolone may increase the hypoglycemic activities of Albiglutide; Paroxetine may increase the hypoglycemic activities of Albiglutide; Pegvisomant may increase the hypoglycemic activities of Albiglutide. | Glucagon-like peptide 1 receptor | Eperzan | Glaxosmithkline Inc | Glaxosmithkline Inc | NA | NA | 50 mg | powder for solution | Subcutaneous | NA | NA | NA | NA | NA | NA |
| 10703 | Th1161 | Albiglutide | >Th1161_Albiglutide HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRHGEGTFTSDVSSYLEGQAAKEFIAWLVKGRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL | 72971 | C3232H5032N864O979S42 | NA | NA | NA | 4-7 days. | Albiglutide is a glucagon-like peptide-1 agonist (GLP-1) biologic drug indicated in the treatment of type 2 diabetes. It is marketed under the brands Eperzan and Tanzeum by GSK (GlaxoSmithKline). It is a dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin. Albiglutide was approved on April 15, 2014 by the FDA. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | It lowers fasting glucose and reduces postprandial glucose excursions in patients with type 2 diabetes mellitus. The majority of the observed reduction in fasting plasma glucose occurs after a single dose, consistent with the pharmacokinetic profile of albiglutide. | Albiglutide is an agonist of the GLP-1 (glucagon-like peptide 1) receptor and augments glucose-dependent insulin secretion. Albiglutide also slows gastric emptying. | -RISK OF THYROID C-CELL TUMORS -Albiglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with Albiglutide. | Biotransformation studies have not been performed. Because albiglutide is an albumin fusion protein, it likely follows a metabolic pathway similar to native human serum albumin, which is catabolized primarily in the vascular endothelium. | Maximum concentrations of albiglutide were reached at 3 to 5 days post-dosing following a single 30mg dose. The mean peak concentration (Cmax) and mean area under the time-concentration curve (AUC) of albiglutide were 1.74 mcg/mL and 465 mcg.h/mL, respectively | 11 L. | 67 mL/h. | Drugs used in diabetes; alimentary tract and metabolism; blood glucose lowering drugs, excl. insulins. | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Albiglutide; Albiglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Albiglutide; Albiglutide may increase the hypoglycemic activities of Insulin Regular; Albiglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Albiglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Albiglutide; Oxandrolone may increase the hypoglycemic activities of Albiglutide; Paroxetine may increase the hypoglycemic activities of Albiglutide; Pegvisomant may increase the hypoglycemic activities of Albiglutide. | Glucagon-like peptide 1 receptor | Eperzan | Glaxosmithkline Inc | Glaxosmithkline Inc | NA | NA | 30 mg | powder for solution | Subcutaneous | NA | NA | NA | NA | NA | NA |
| 10704 | Th1161 | Albiglutide | >Th1161_Albiglutide HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRHGEGTFTSDVSSYLEGQAAKEFIAWLVKGRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL | 72972 | C3232H5032N864O979S43 | NA | NA | NA | 4-7 days. | Albiglutide is a glucagon-like peptide-1 agonist (GLP-1) biologic drug indicated in the treatment of type 2 diabetes. It is marketed under the brands Eperzan and Tanzeum by GSK (GlaxoSmithKline). It is a dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin. Albiglutide was approved on April 15, 2014 by the FDA. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | It lowers fasting glucose and reduces postprandial glucose excursions in patients with type 2 diabetes mellitus. The majority of the observed reduction in fasting plasma glucose occurs after a single dose, consistent with the pharmacokinetic profile of albiglutide. | Albiglutide is an agonist of the GLP-1 (glucagon-like peptide 1) receptor and augments glucose-dependent insulin secretion. Albiglutide also slows gastric emptying. | -RISK OF THYROID C-CELL TUMORS -Albiglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with Albiglutide. | Biotransformation studies have not been performed. Because albiglutide is an albumin fusion protein, it likely follows a metabolic pathway similar to native human serum albumin, which is catabolized primarily in the vascular endothelium. | Maximum concentrations of albiglutide were reached at 3 to 5 days post-dosing following a single 30mg dose. The mean peak concentration (Cmax) and mean area under the time-concentration curve (AUC) of albiglutide were 1.74 mcg/mL and 465 mcg.h/mL, respectively | 11 L. | 67 mL/h. | Drugs used in diabetes; alimentary tract and metabolism; blood glucose lowering drugs, excl. insulins. | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Albiglutide; Albiglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Albiglutide; Albiglutide may increase the hypoglycemic activities of Insulin Regular; Albiglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Albiglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Albiglutide; Oxandrolone may increase the hypoglycemic activities of Albiglutide; Paroxetine may increase the hypoglycemic activities of Albiglutide; Pegvisomant may increase the hypoglycemic activities of Albiglutide. | Glucagon-like peptide 1 receptor | Tanzeum | Glaxo Smith Kline Llc | Glaxo Smith Kline Llc | A GLP-1 receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus | NA | 30 mg/.5mL | injection, powder, lyophilized, for solution | Subcutaneous | The recommended dosage of TANZEUM is 30 mg once weekly given as a subcutaneous injection in the abdomen, thigh, or upper arm region. The dosage may be increased to 50 mg once weekly if the glycemic response is inadequate. | Contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); in patients with a prior serious hypersensitivity reaction to albiglutide or to any of the product components | Risk of Thyroid C-cell Tumors; Acute Pancreatitis; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin ; Hypersensitivity Reactions; Renal Impairment. | Link | NA | NA |
| 10705 | Th1161 | Albiglutide | >Th1161_Albiglutide HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRHGEGTFTSDVSSYLEGQAAKEFIAWLVKGRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL | 72973 | C3232H5032N864O979S44 | NA | NA | NA | 4-7 days. | Albiglutide is a glucagon-like peptide-1 agonist (GLP-1) biologic drug indicated in the treatment of type 2 diabetes. It is marketed under the brands Eperzan and Tanzeum by GSK (GlaxoSmithKline). It is a dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin. Albiglutide was approved on April 15, 2014 by the FDA. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | It lowers fasting glucose and reduces postprandial glucose excursions in patients with type 2 diabetes mellitus. The majority of the observed reduction in fasting plasma glucose occurs after a single dose, consistent with the pharmacokinetic profile of albiglutide. | Albiglutide is an agonist of the GLP-1 (glucagon-like peptide 1) receptor and augments glucose-dependent insulin secretion. Albiglutide also slows gastric emptying. | -RISK OF THYROID C-CELL TUMORS -Albiglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with Albiglutide. | Biotransformation studies have not been performed. Because albiglutide is an albumin fusion protein, it likely follows a metabolic pathway similar to native human serum albumin, which is catabolized primarily in the vascular endothelium. | Maximum concentrations of albiglutide were reached at 3 to 5 days post-dosing following a single 30mg dose. The mean peak concentration (Cmax) and mean area under the time-concentration curve (AUC) of albiglutide were 1.74 mcg/mL and 465 mcg.h/mL, respectively | 11 L. | 67 mL/h. | Drugs used in diabetes; alimentary tract and metabolism; blood glucose lowering drugs, excl. insulins. | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Albiglutide; Albiglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Albiglutide; Albiglutide may increase the hypoglycemic activities of Insulin Regular; Albiglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Albiglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Albiglutide; Oxandrolone may increase the hypoglycemic activities of Albiglutide; Paroxetine may increase the hypoglycemic activities of Albiglutide; Pegvisomant may increase the hypoglycemic activities of Albiglutide. | Glucagon-like peptide 1 receptor | Tanzeum | Glaxo Smith Kline Llc | Glaxo Smith Kline Llc | A GLP-1 receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus | NA | 50 mg/.5mL | injection, powder, lyophilized, for solution | Subcutaneous | The recommended dosage of TANZEUM is 30 mg once weekly given as a subcutaneous injection in the abdomen, thigh, or upper arm region. The dosage may be increased to 50 mg once weekly if the glycemic response is inadequate. | Contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); in patients with a prior serious hypersensitivity reaction to albiglutide or to any of the product components | Risk of Thyroid C-cell Tumors; Acute Pancreatitis; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin ; Hypersensitivity Reactions; Renal Impairment. | Link | NA | NA |
| 10706 | Th1162 | Alirocumab | NA | 146000 | C6472H9996N1736O2032S42 | NA | NA | NA | In monotherapy, the median half-life of alirocumab at steady state was 17–20 days in patients receiving alirocumab at SC doses of 75 or 150 mg every 2 weeks. | Alirocumab is a biopharmaceutical drug approved by the FDA in July 2015 as a second line treatment for high cholesterol for adults whose LDL-cholesterol (LDL-C) is not controlled by diet and statin treatment. It is a human monoclonal antibody administered by subcutaneous injection that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. PCSK9 inhibition facilitates more LDL-C clearance from the blood. | Alirocumab is indicated as an adjunct to diet and maximally tolerated statin therapy in adults who require additional LDL-cholesterol (LDL-C) lowering due to heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease. | Alirocumab reduces levels of PCSK9 in a concentration-dependent manner. | Alirocumab is a fully human IgG1 monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have gain of function mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease. | NA | Antibodies are generally metabolized by the reticuloendothelial system and degraded into small peptides and individual amino acids - therefore specific metabolism studies were not conducted. Alirocumab did not show evidence of affecting CYP 450 enzymes or transporter proteins in co-administration with statins. | Following subcutaneous (SC) administration, alirocumab is absorbed into the bloodstream and maximum concentrations are reached at a median time of 3-7 days. The absolute availability after SC administration was 85%. | Alirocumab is mainly distributed through the circulatory system, with minimal extravascular distribution. | NA | NA | NA | NA | NA | The risk or severity of adverse effects can be increased when Alirocumab is combined with Belimumab. | Proprotein convertase subtilisin/kexin type 9 | Praluent | Sanofi Aventis U.S. Llc | Sanofi Aventis U.S. Llc | It is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C. | NA | 75 mg/mL | injection, solution | Subcutaneous | The recommended starting dose of PRALUENT is 75 mg administered subcutaneously once every 2 weeks, since the majority of patients achieve sufficient LDL-C reduction with this dosage. If the LDL-C response is inadequate, the dosage may be increased to the maximum dosage of 150 mg administered every 2 weeks. | It is contraindicated in patients with a history of a serious hypersensitivity reaction to PRALUENT. Reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization. | Allergic Reactions | Link | NA | NA |
| 10707 | Th1162 | Alirocumab | NA | 146001 | C6472H9996N1736O2032S43 | NA | NA | NA | In monotherapy, the median half-life of alirocumab at steady state was 17–20 days in patients receiving alirocumab at SC doses of 75 or 150 mg every 2 weeks. | Alirocumab is a biopharmaceutical drug approved by the FDA in July 2015 as a second line treatment for high cholesterol for adults whose LDL-cholesterol (LDL-C) is not controlled by diet and statin treatment. It is a human monoclonal antibody administered by subcutaneous injection that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. PCSK9 inhibition facilitates more LDL-C clearance from the blood. | Alirocumab is indicated as an adjunct to diet and maximally tolerated statin therapy in adults who require additional LDL-cholesterol (LDL-C) lowering due to heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease. | Alirocumab reduces levels of PCSK9 in a concentration-dependent manner. | Alirocumab is a fully human IgG1 monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have gain of function mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease. | NA | Antibodies are generally metabolized by the reticuloendothelial system and degraded into small peptides and individual amino acids - therefore specific metabolism studies were not conducted. Alirocumab did not show evidence of affecting CYP 450 enzymes or transporter proteins in co-administration with statins. | Following subcutaneous (SC) administration, alirocumab is absorbed into the bloodstream and maximum concentrations are reached at a median time of 3-7 days. The absolute availability after SC administration was 85%. | Alirocumab is mainly distributed through the circulatory system, with minimal extravascular distribution. | NA | NA | NA | NA | NA | The risk or severity of adverse effects can be increased when Alirocumab is combined with Belimumab. | Proprotein convertase subtilisin/kexin type 9 | Praluent | Sanofi Aventis Canada Inc | Sanofi Aventis Canada Inc | It is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C. | NA | 150 mg | solution | Subcutaneous | The recommended starting dose of PRALUENT is 75 mg administered subcutaneously once every 2 weeks, since the majority of patients achieve sufficient LDL-C reduction with this dosage. If the LDL-C response is inadequate, the dosage may be increased to the maximum dosage of 150 mg administered every 2 weeks. | It is contraindicated in patients with a history of a serious hypersensitivity reaction to PRALUENT. Reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization. | Allergic Reactions | Link | NA | NA |
| 10708 | Th1162 | Alirocumab | NA | 146002 | C6472H9996N1736O2032S44 | NA | NA | NA | In monotherapy, the median half-life of alirocumab at steady state was 17–20 days in patients receiving alirocumab at SC doses of 75 or 150 mg every 2 weeks. | Alirocumab is a biopharmaceutical drug approved by the FDA in July 2015 as a second line treatment for high cholesterol for adults whose LDL-cholesterol (LDL-C) is not controlled by diet and statin treatment. It is a human monoclonal antibody administered by subcutaneous injection that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. PCSK9 inhibition facilitates more LDL-C clearance from the blood. | Alirocumab is indicated as an adjunct to diet and maximally tolerated statin therapy in adults who require additional LDL-cholesterol (LDL-C) lowering due to heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease. | Alirocumab reduces levels of PCSK9 in a concentration-dependent manner. | Alirocumab is a fully human IgG1 monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have gain of function mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease. | NA | Antibodies are generally metabolized by the reticuloendothelial system and degraded into small peptides and individual amino acids - therefore specific metabolism studies were not conducted. Alirocumab did not show evidence of affecting CYP 450 enzymes or transporter proteins in co-administration with statins. | Following subcutaneous (SC) administration, alirocumab is absorbed into the bloodstream and maximum concentrations are reached at a median time of 3-7 days. The absolute availability after SC administration was 85%. | Alirocumab is mainly distributed through the circulatory system, with minimal extravascular distribution. | NA | NA | NA | NA | NA | The risk or severity of adverse effects can be increased when Alirocumab is combined with Belimumab. | Proprotein convertase subtilisin/kexin type 9 | Praluent | Sanofi Aventis Canada Inc | Sanofi Aventis Canada Inc | It is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C. | NA | 75 mg | solution | Subcutaneous | The recommended starting dose of PRALUENT is 75 mg administered subcutaneously once every 2 weeks, since the majority of patients achieve sufficient LDL-C reduction with this dosage. If the LDL-C response is inadequate, the dosage may be increased to the maximum dosage of 150 mg administered every 2 weeks. | It is contraindicated in patients with a history of a serious hypersensitivity reaction to PRALUENT. Reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization. | Allergic Reactions | Link | NA | NA |
| 10709 | Th1162 | Alirocumab | NA | 146005 | C6472H9996N1736O2032S47 | NA | NA | NA | In monotherapy, the median half-life of alirocumab at steady state was 17–20 days in patients receiving alirocumab at SC doses of 75 or 150 mg every 2 weeks. | Alirocumab is a biopharmaceutical drug approved by the FDA in July 2015 as a second line treatment for high cholesterol for adults whose LDL-cholesterol (LDL-C) is not controlled by diet and statin treatment. It is a human monoclonal antibody administered by subcutaneous injection that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. PCSK9 inhibition facilitates more LDL-C clearance from the blood. | Alirocumab is indicated as an adjunct to diet and maximally tolerated statin therapy in adults who require additional LDL-cholesterol (LDL-C) lowering due to heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease. | Alirocumab reduces levels of PCSK9 in a concentration-dependent manner. | Alirocumab is a fully human IgG1 monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have gain of function mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease. | NA | Antibodies are generally metabolized by the reticuloendothelial system and degraded into small peptides and individual amino acids - therefore specific metabolism studies were not conducted. Alirocumab did not show evidence of affecting CYP 450 enzymes or transporter proteins in co-administration with statins. | Following subcutaneous (SC) administration, alirocumab is absorbed into the bloodstream and maximum concentrations are reached at a median time of 3-7 days. The absolute availability after SC administration was 85%. | Alirocumab is mainly distributed through the circulatory system, with minimal extravascular distribution. | NA | NA | NA | NA | NA | The risk or severity of adverse effects can be increased when Alirocumab is combined with Belimumab. | Proprotein convertase subtilisin/kexin type 9 | Praluent | Sanofi Aventis U.S. Llc | Sanofi Aventis U.S. Llc | It is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C. | NA | 150 mg/mL | injection, solution | Subcutaneous | The recommended starting dose of PRALUENT is 75 mg administered subcutaneously once every 2 weeks, since the majority of patients achieve sufficient LDL-C reduction with this dosage. If the LDL-C response is inadequate, the dosage may be increased to the maximum dosage of 150 mg administered every 2 weeks. | It is contraindicated in patients with a history of a serious hypersensitivity reaction to PRALUENT. Reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization. | Allergic Reactions | Link | NA | NA |
| 10756 | Th1176 | Dulaglutide | >Th1176_Dulaglutide HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 59669.81 | C2646H4044N704O836S18 | NA | NA | NA | Approximately 5 days. | Dulaglutide is a novel glucagon-like peptide-1 agonist (GLP-1) biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. Dulaglutide is indicated in the treatment of type 2 diabetes and can be used once a week. It was approved by the FDA in September 2014. Dulaglutide is manufactured and marketed by Eli Lily under the brand Trulicityâ„¢. It is not known if dulaglutide can increase the risk of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and is thus not recommended for use in populations with a personal or family history of these conditions. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying. | Dulaglutide is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying. | LD50 information for dulaglutide is not readily available in the literature.[L34685] Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms.[L34670] Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed.[L30380] | Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways.[L30380] | Dulaglutide is slowly absorbed after subcutaneous injection.[L34670] In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing.[A234419] The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively.[L30380] | The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L.[L30380] | The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study.[L30380] | Alimentary Tract and Metabolism,Amino Acids, Peptides, and Proteins,Blood Glucose Lowering Agents,Blood Proteins,Drugs Used in Diabetes,Gastrointestinal Hormones,Globulins,GLP-1 Agonists,Glucagon-like peptide-1 (GLP-1) analogues,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Immunoglobulin Fragments,Immunoglobulins,Immunoproteins,Incretin Mimetics,Pancreatic Hormones,Peptide Fragments,Peptide Hormones,Peptides,Proglucagon,Protein Precursors,Proteins,Recombinant Proteins,Serum Globulins | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Insulin Regular; Dulaglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Dulaglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Dulaglutide; Oxandrolone may increase the hypoglycemic activities of Dulaglutide; Paroxetine may increase the hypoglycemic activities of Dulaglutide; Pegvisomant may increase the hypoglycemic activities of Dulaglutide. | Glucagon-like peptide 1 receptor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10757 | Th1176 | Dulaglutide | >Th1176_Dulaglutide HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 59669.81 | C2646H4044N704O836S19 | NA | NA | NA | Approximately 5 days. | Dulaglutide is a novel glucagon-like peptide-1 agonist (GLP-1) biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. Dulaglutide is indicated in the treatment of type 2 diabetes and can be used once a week. It was approved by the FDA in September 2014. Dulaglutide is manufactured and marketed by Eli Lily under the brand Trulicityâ„¢. It is not known if dulaglutide can increase the risk of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and is thus not recommended for use in populations with a personal or family history of these conditions. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying. | Dulaglutide is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying. | LD50 information for dulaglutide is not readily available in the literature.[L34685] Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms.[L34670] Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed.[L30380] | Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways.[L30380] | Dulaglutide is slowly absorbed after subcutaneous injection.[L34670] In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing.[A234419] The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively.[L30380] | The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L.[L30380] | The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study.[L30380] | Alimentary Tract and Metabolism,Amino Acids, Peptides, and Proteins,Blood Glucose Lowering Agents,Blood Proteins,Drugs Used in Diabetes,Gastrointestinal Hormones,Globulins,GLP-1 Agonists,Glucagon-like peptide-1 (GLP-1) analogues,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Immunoglobulin Fragments,Immunoglobulins,Immunoproteins,Incretin Mimetics,Pancreatic Hormones,Peptide Fragments,Peptide Hormones,Peptides,Proglucagon,Protein Precursors,Proteins,Recombinant Proteins,Serum Globulins | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Insulin Regular; Dulaglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Dulaglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Dulaglutide; Oxandrolone may increase the hypoglycemic activities of Dulaglutide; Paroxetine may increase the hypoglycemic activities of Dulaglutide; Pegvisomant may increase the hypoglycemic activities of Dulaglutide. | Glucagon-like peptide 1 receptor | Trulicity | Eli Lilly and Company | Eli Lilly and Company | TRULICITYâ„¢ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | NA | TRULICITY solution contains 0.75 mg or 1.5 mg of dulaglutide. Each single-dose pen or prefilled syringe contains 0.5 mL of solution and the following excipients: citric acid anhydrous (0.07 mg), mannitol (23.2 mg), polysorbate 80 (0.10 mg), trisodium citrate dihydrate (1.37 mg), in water for injection. | Solution, Injection | Subcutaneous | The recommended initiating dose of TRULICITY is 0.75 mg once weekly. The dose may be increased to 1.5 mg once weekly for additional glycemic control. The maximum recommended dose is 1.5 mg once weekly. Administer TRULICITY once weekly, any time of day, with or without food. TRULICITY should be injected subcutaneously in the abdomen, thigh, or upper arm. If a dose is missed, instruct patients to administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. The day of weekly administration can be changed if necessary as long as the last dose was administered 3 or more days before. | TRULICITY is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); TRULICITY is also contraindicated in patients with a prior serious hypersensitivity reaction to dulaglutide or to any of the product components | Risk of Thyroid C-cell Tumors; Pancreatitis; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin; Hypersensitivity reactions; Renal impairment; Severe Gastrointestinal Disease. | Link | NA | NA |
| 10758 | Th1176 | Dulaglutide | >Th1176_Dulaglutide HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 59669.81 | C2646H4044N704O836S20 | NA | NA | NA | Approximately 5 days. | Dulaglutide is a novel glucagon-like peptide-1 agonist (GLP-1) biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. Dulaglutide is indicated in the treatment of type 2 diabetes and can be used once a week. It was approved by the FDA in September 2014. Dulaglutide is manufactured and marketed by Eli Lily under the brand Trulicityâ„¢. It is not known if dulaglutide can increase the risk of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and is thus not recommended for use in populations with a personal or family history of these conditions. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying. | Dulaglutide is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying. | LD50 information for dulaglutide is not readily available in the literature.[L34685] Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms.[L34670] Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed.[L30380] | Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways.[L30380] | Dulaglutide is slowly absorbed after subcutaneous injection.[L34670] In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing.[A234419] The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively.[L30380] | The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L.[L30380] | The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study.[L30380] | Alimentary Tract and Metabolism,Amino Acids, Peptides, and Proteins,Blood Glucose Lowering Agents,Blood Proteins,Drugs Used in Diabetes,Gastrointestinal Hormones,Globulins,GLP-1 Agonists,Glucagon-like peptide-1 (GLP-1) analogues,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Immunoglobulin Fragments,Immunoglobulins,Immunoproteins,Incretin Mimetics,Pancreatic Hormones,Peptide Fragments,Peptide Hormones,Peptides,Proglucagon,Protein Precursors,Proteins,Recombinant Proteins,Serum Globulins | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Insulin Regular; Dulaglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Dulaglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Dulaglutide; Oxandrolone may increase the hypoglycemic activities of Dulaglutide; Paroxetine may increase the hypoglycemic activities of Dulaglutide; Pegvisomant may increase the hypoglycemic activities of Dulaglutide. | Glucagon-like peptide 1 receptor | Trulicity | Eli Lilly Canada Inc | Eli Lilly Canada Inc | TRULICITYâ„¢ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | NA | TRULICITY solution contains 0.75 mg or 1.5 mg of dulaglutide. Each single-dose pen or prefilled syringe contains 0.5 mL of solution and the following excipients: citric acid anhydrous (0.07 mg), mannitol (23.2 mg), polysorbate 80 (0.10 mg), trisodium citrate dihydrate (1.37 mg), in water for injection. | Solution | Subcutaneous | The recommended initiating dose of TRULICITY is 0.75 mg once weekly. The dose may be increased to 1.5 mg once weekly for additional glycemic control. The maximum recommended dose is 1.5 mg once weekly. Administer TRULICITY once weekly, any time of day, with or without food. TRULICITY should be injected subcutaneously in the abdomen, thigh, or upper arm. If a dose is missed, instruct patients to administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. The day of weekly administration can be changed if necessary as long as the last dose was administered 3 or more days before. | TRULICITY is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); TRULICITY is also contraindicated in patients with a prior serious hypersensitivity reaction to dulaglutide or to any of the product components | Risk of Thyroid C-cell Tumors; Pancreatitis; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin; Hypersensitivity reactions; Renal impairment; Severe Gastrointestinal Disease. | Link | NA | NA |
| 10759 | Th1176 | Dulaglutide | >Th1176_Dulaglutide HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 59669.81 | C2646H4044N704O836S21 | NA | NA | NA | Approximately 5 days. | Dulaglutide is a novel glucagon-like peptide-1 agonist (GLP-1) biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. Dulaglutide is indicated in the treatment of type 2 diabetes and can be used once a week. It was approved by the FDA in September 2014. Dulaglutide is manufactured and marketed by Eli Lily under the brand Trulicityâ„¢. It is not known if dulaglutide can increase the risk of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and is thus not recommended for use in populations with a personal or family history of these conditions. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying. | Dulaglutide is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying. | LD50 information for dulaglutide is not readily available in the literature.[L34685] Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms.[L34670] Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed.[L30380] | Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways.[L30380] | Dulaglutide is slowly absorbed after subcutaneous injection.[L34670] In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing.[A234419] The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively.[L30380] | The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L.[L30380] | The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study.[L30380] | Alimentary Tract and Metabolism,Amino Acids, Peptides, and Proteins,Blood Glucose Lowering Agents,Blood Proteins,Drugs Used in Diabetes,Gastrointestinal Hormones,Globulins,GLP-1 Agonists,Glucagon-like peptide-1 (GLP-1) analogues,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Immunoglobulin Fragments,Immunoglobulins,Immunoproteins,Incretin Mimetics,Pancreatic Hormones,Peptide Fragments,Peptide Hormones,Peptides,Proglucagon,Protein Precursors,Proteins,Recombinant Proteins,Serum Globulins | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Insulin Regular; Dulaglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Dulaglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Dulaglutide; Oxandrolone may increase the hypoglycemic activities of Dulaglutide; Paroxetine may increase the hypoglycemic activities of Dulaglutide; Pegvisomant may increase the hypoglycemic activities of Dulaglutide. | Glucagon-like peptide 1 receptor | Trulicity | Eli Lilly Canada Inc | Eli Lilly Canada Inc | TRULICITYâ„¢ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | NA | TRULICITY solution contains 0.75 mg or 1.5 mg of dulaglutide. Each single-dose pen or prefilled syringe contains 0.5 mL of solution and the following excipients: citric acid anhydrous (0.07 mg), mannitol (23.2 mg), polysorbate 80 (0.10 mg), trisodium citrate dihydrate (1.37 mg), in water for injection. | Solution | Subcutaneous | The recommended initiating dose of TRULICITY is 0.75 mg once weekly. The dose may be increased to 1.5 mg once weekly for additional glycemic control. The maximum recommended dose is 1.5 mg once weekly. Administer TRULICITY once weekly, any time of day, with or without food. TRULICITY should be injected subcutaneously in the abdomen, thigh, or upper arm. If a dose is missed, instruct patients to administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. The day of weekly administration can be changed if necessary as long as the last dose was administered 3 or more days before. | TRULICITY is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); TRULICITY is also contraindicated in patients with a prior serious hypersensitivity reaction to dulaglutide or to any of the product components | Risk of Thyroid C-cell Tumors; Pancreatitis; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin; Hypersensitivity reactions; Renal impairment; Severe Gastrointestinal Disease. | Link | NA | NA |
| 10760 | Th1176 | Dulaglutide | >Th1176_Dulaglutide HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 59669.81 | C2646H4044N704O836S22 | NA | NA | NA | Approximately 5 days. | Dulaglutide is a novel glucagon-like peptide-1 agonist (GLP-1) biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. Dulaglutide is indicated in the treatment of type 2 diabetes and can be used once a week. It was approved by the FDA in September 2014. Dulaglutide is manufactured and marketed by Eli Lily under the brand Trulicityâ„¢. It is not known if dulaglutide can increase the risk of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and is thus not recommended for use in populations with a personal or family history of these conditions. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying. | Dulaglutide is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying. | LD50 information for dulaglutide is not readily available in the literature.[L34685] Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms.[L34670] Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed.[L30380] | Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways.[L30380] | Dulaglutide is slowly absorbed after subcutaneous injection.[L34670] In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing.[A234419] The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively.[L30380] | The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L.[L30380] | The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study.[L30380] | Alimentary Tract and Metabolism,Amino Acids, Peptides, and Proteins,Blood Glucose Lowering Agents,Blood Proteins,Drugs Used in Diabetes,Gastrointestinal Hormones,Globulins,GLP-1 Agonists,Glucagon-like peptide-1 (GLP-1) analogues,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Immunoglobulin Fragments,Immunoglobulins,Immunoproteins,Incretin Mimetics,Pancreatic Hormones,Peptide Fragments,Peptide Hormones,Peptides,Proglucagon,Protein Precursors,Proteins,Recombinant Proteins,Serum Globulins | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Insulin Regular; Dulaglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Dulaglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Dulaglutide; Oxandrolone may increase the hypoglycemic activities of Dulaglutide; Paroxetine may increase the hypoglycemic activities of Dulaglutide; Pegvisomant may increase the hypoglycemic activities of Dulaglutide. | Glucagon-like peptide 1 receptor | Trulicity | Eli Lilly Canada Inc | Eli Lilly Canada Inc | TRULICITYâ„¢ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | NA | TRULICITY solution contains 0.75 mg or 1.5 mg of dulaglutide. Each single-dose pen or prefilled syringe contains 0.5 mL of solution and the following excipients: citric acid anhydrous (0.07 mg), mannitol (23.2 mg), polysorbate 80 (0.10 mg), trisodium citrate dihydrate (1.37 mg), in water for injection. | Solution | Subcutaneous | The recommended initiating dose of TRULICITY is 0.75 mg once weekly. The dose may be increased to 1.5 mg once weekly for additional glycemic control. The maximum recommended dose is 1.5 mg once weekly. Administer TRULICITY once weekly, any time of day, with or without food. TRULICITY should be injected subcutaneously in the abdomen, thigh, or upper arm. If a dose is missed, instruct patients to administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. The day of weekly administration can be changed if necessary as long as the last dose was administered 3 or more days before. | TRULICITY is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); TRULICITY is also contraindicated in patients with a prior serious hypersensitivity reaction to dulaglutide or to any of the product components | Risk of Thyroid C-cell Tumors; Pancreatitis; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin; Hypersensitivity reactions; Renal impairment; Severe Gastrointestinal Disease. | Link | NA | NA |
| 10761 | Th1176 | Dulaglutide | >Th1176_Dulaglutide HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 59669.81 | C2646H4044N704O836S23 | NA | NA | NA | Approximately 5 days. | Dulaglutide is a novel glucagon-like peptide-1 agonist (GLP-1) biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. Dulaglutide is indicated in the treatment of type 2 diabetes and can be used once a week. It was approved by the FDA in September 2014. Dulaglutide is manufactured and marketed by Eli Lily under the brand Trulicityâ„¢. It is not known if dulaglutide can increase the risk of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and is thus not recommended for use in populations with a personal or family history of these conditions. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying. | Dulaglutide is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying. | LD50 information for dulaglutide is not readily available in the literature.[L34685] Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms.[L34670] Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed.[L30380] | Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways.[L30380] | Dulaglutide is slowly absorbed after subcutaneous injection.[L34670] In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing.[A234419] The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively.[L30380] | The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L.[L30380] | The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study.[L30380] | Alimentary Tract and Metabolism,Amino Acids, Peptides, and Proteins,Blood Glucose Lowering Agents,Blood Proteins,Drugs Used in Diabetes,Gastrointestinal Hormones,Globulins,GLP-1 Agonists,Glucagon-like peptide-1 (GLP-1) analogues,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Immunoglobulin Fragments,Immunoglobulins,Immunoproteins,Incretin Mimetics,Pancreatic Hormones,Peptide Fragments,Peptide Hormones,Peptides,Proglucagon,Protein Precursors,Proteins,Recombinant Proteins,Serum Globulins | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Insulin Regular; Dulaglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Dulaglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Dulaglutide; Oxandrolone may increase the hypoglycemic activities of Dulaglutide; Paroxetine may increase the hypoglycemic activities of Dulaglutide; Pegvisomant may increase the hypoglycemic activities of Dulaglutide. | Glucagon-like peptide 1 receptor | Trulicity | Eli Lilly Canada Inc | Eli Lilly Canada Inc | TRULICITYâ„¢ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | NA | TRULICITY solution contains 0.75 mg or 1.5 mg of dulaglutide. Each single-dose pen or prefilled syringe contains 0.5 mL of solution and the following excipients: citric acid anhydrous (0.07 mg), mannitol (23.2 mg), polysorbate 80 (0.10 mg), trisodium citrate dihydrate (1.37 mg), in water for injection. | Solution | Subcutaneous | The recommended initiating dose of TRULICITY is 0.75 mg once weekly. The dose may be increased to 1.5 mg once weekly for additional glycemic control. The maximum recommended dose is 1.5 mg once weekly. Administer TRULICITY once weekly, any time of day, with or without food. TRULICITY should be injected subcutaneously in the abdomen, thigh, or upper arm. If a dose is missed, instruct patients to administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. The day of weekly administration can be changed if necessary as long as the last dose was administered 3 or more days before. | TRULICITY is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); TRULICITY is also contraindicated in patients with a prior serious hypersensitivity reaction to dulaglutide or to any of the product components | Risk of Thyroid C-cell Tumors; Pancreatitis; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin; Hypersensitivity reactions; Renal impairment; Severe Gastrointestinal Disease. | Link | NA | NA |
| 10762 | Th1176 | Dulaglutide | >Th1176_Dulaglutide HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 59670.81 | C2646H4044N704O836S24 | NA | NA | NA | Approximately 5 days. | Dulaglutide is a novel glucagon-like peptide-1 agonist (GLP-1) biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. Dulaglutide is indicated in the treatment of type 2 diabetes and can be used once a week. It was approved by the FDA in September 2014. Dulaglutide is manufactured and marketed by Eli Lily under the brand Trulicityâ„¢. It is not known if dulaglutide can increase the risk of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and is thus not recommended for use in populations with a personal or family history of these conditions. | Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying. | Dulaglutide is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying. | LD50 information for dulaglutide is not readily available in the literature.[L34685] Cases of overdose with dulaglutide have resulted in gastrointestinal disturbance. Appropriate supportive treatment is recommended to manage signs and symptoms.[L34670] Additionally, hypoglycemia has been observed after an overdose with dulaglutide; frequent plasma glucose monitoring should be performed.[L30380] | Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways.[L30380] | Dulaglutide is slowly absorbed after subcutaneous injection.[L34670] In a pharmacokinetic study of 20 healthy adults, Cmax occurred within 24-48 hours after dosing.[A234419] The average absolute bioavailability of dulaglutide after subcutaneous injections of single 0.75 mg and 1.5 mg doses was 65% and 47%, respectively.[L30380] | The apparent volume of distribution of dulaglutide was 3.09 L in a pharmacokinetic study; the apparent population mean peripheral volume of distribution was approximately 6 L.[L30380] | The apparent population mean clearance of dulaglutide was 0.142 L/h in a pharmacokinetic study.[L30380] | Alimentary Tract and Metabolism,Amino Acids, Peptides, and Proteins,Blood Glucose Lowering Agents,Blood Proteins,Drugs Used in Diabetes,Gastrointestinal Hormones,Globulins,GLP-1 Agonists,Glucagon-like peptide-1 (GLP-1) analogues,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Immunoglobulin Fragments,Immunoglobulins,Immunoproteins,Incretin Mimetics,Pancreatic Hormones,Peptide Fragments,Peptide Hormones,Peptides,Proglucagon,Protein Precursors,Proteins,Recombinant Proteins,Serum Globulins | NA | NA | NA | Acetylsalicylic acid may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Chlorpropamide; Dihydrotestosterone may increase the hypoglycemic activities of Dulaglutide; Dulaglutide may increase the hypoglycemic activities of Insulin Regular; Dulaglutide may increase the hypoglycemic activities of Insulin Lispro; The therapeutic efficacy of Dulaglutide can be decreased when used in combination with Leuprolide; Lipoic Acid may increase the hypoglycemic activities of Dulaglutide; Oxandrolone may increase the hypoglycemic activities of Dulaglutide; Paroxetine may increase the hypoglycemic activities of Dulaglutide; Pegvisomant may increase the hypoglycemic activities of Dulaglutide. | Glucagon-like peptide 1 receptor | Trulicity | Eli Lilly and Company | Eli Lilly and Company | TRULICITYâ„¢ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. | NA | TRULICITY solution contains 0.75 mg or 1.5 mg of dulaglutide. Each single-dose pen or prefilled syringe contains 0.5 mL of solution and the following excipients: citric acid anhydrous (0.07 mg), mannitol (23.2 mg), polysorbate 80 (0.10 mg), trisodium citrate dihydrate (1.37 mg), in water for injection. | Solution, Injection | Subcutaneous | The recommended initiating dose of TRULICITY is 0.75 mg once weekly. The dose may be increased to 1.5 mg once weekly for additional glycemic control. The maximum recommended dose is 1.5 mg once weekly. Administer TRULICITY once weekly, any time of day, with or without food. TRULICITY should be injected subcutaneously in the abdomen, thigh, or upper arm. If a dose is missed, instruct patients to administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. The day of weekly administration can be changed if necessary as long as the last dose was administered 3 or more days before. | TRULICITY is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); TRULICITY is also contraindicated in patients with a prior serious hypersensitivity reaction to dulaglutide or to any of the product components | Risk of Thyroid C-cell Tumors; Pancreatitis; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin; Hypersensitivity reactions; Renal impairment; Severe Gastrointestinal Disease. | Link | NA | NA |
| 10808 | Th1188 | Hyaluronidase (Human Recombinant) | NA | 61000 | NA | NA | NA | NA | Hyaluronidase has a half life of two minutes, but a duration of action of 24-48 hours due to its high potency | A purified preparation of the enzyme recombinant human hyaluronidase. Hyaluronidase (Human Recombinant) is produced by genetically engineered Chinese Hamster Ovary (CHO) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). The purified hyaluronidase glycoprotein contains 447 amino acids with an approximate molecular weight of 61,000 Daltons. | Indicated as an adjuvant to increase the absorption and dispersion of other injected drugs; for hypodermoclysis; and as an adjunct in subcutaneous urography for improving resorption of radiopaque agents. | Hyaluronidase hydrolyzes hyaluronic acid and increase diffusion of injected drugs, thus facilitating their absorption. Hyaluronidase is used for enhancing absorption and distribution of other injected drugs. | The family of hyaluronidase enzymes hydrolyzes hyaluronic acid (a glucoseaminoglycan) which is a major constituent of the interstitial barrier. Hyaluronidase (Human Recombinant) is a highly purified recombinant human hyluronidase which lowers the viscosity of the interstitial barrier by breaking down hyaluronic acid and is under investigation as a chemoadjuvant to facilitate local interstitial drug delivery as well as increase bioavilability. | Data regarding overdose of hyaluronidase is not readily available.[L13338] In the even of an overdose, treat patients with symptomatic and supportive measures. | Data regarding the metabolism of hyaluronidase is not readily available.[L13338] However, protein drugs are expected to be degraded by proteases and other catalytic enzymes to smaller peptides and amino acids.[A182009] | Data regarding the absorption of hyaluronidase are not readily available due to hyaluronidase being inactivated in blood.[L13338] | Data regarding the volume of distribution of hyaluronidase are not readily available due to hyaluronidase being inactivated in blood.[L13338] | Data regarding the clearance of hyaluronidase are not readily available.[L13338] | NA | US7767429 | 8-Mar-2010 | 23-09-2027 | NA | Hyaluronic acid,Transforming growth factor beta-1 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 10833 | Th1199 | Ramucirumab | >Th1199_Ramucirumab EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTDAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 143600 | C6374H9864N1692O1996S46 | NA | NA | NA | 15 days | Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells. VEGFR stimulation also mediates downstream signalling required for angiogenesis and is postulated to be heavily involved in cancer progression, making it a highly likely drug target. In contrast to other agents directed against VEGFR-2, ramucirumab binds a specific epitope on the extracellular domain of VEGFR-2, thereby blocking all VEGF ligands from binding to it. Ramucirumab is indicated for us in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy. | For use in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy. | Ramucirumab inhibits ligandstimulated activation of VEGF Receptor 2, thereby inhibiting ligand-induced proliferation, and migration of human endothelial cells. Ramucirumab inhibited angiogenesis in an in vivo animal model. | Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells. | Ramucirumab packaging includes warnings for arterial thromboembolic events, hypertension, infusion-related reactions, gastrointestinal perforation, clinical deterioration in patients with cirrhosis, and reversible posterior leukoencephalopathy syndrome. The most common reactions observed in single-agent-treated patients at a rate of >10% and >2% higher than placebo were hypertension and diarrhea. The most common adverse reactions observed in patients treated with ramucirumab plus paclitaxel at a rate of of >30% and >2% higher than placebo plus paclitaxel were fatigue, neutropenia, diarrhea, and epistaxis. | NA | NA | 5.5 L | 0.014 L/hour | Antineoplastic and Immunomodulating Agents | US2013067098 | 11-Feb-2011 | 11-Feb-2031 | Belimumab, Pamidronate | Vascular endothelial growth factor receptor 2 | Cyramza | Eli Lilly and Company | Eli Lilly and Company | CYRAMZA®as a single agent, or in combination with paclitaxel, is indicated for the treatment of patients with advanced or metastatic, gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine-or platinum-containing chemotherapy. | NA | 10 mg/mL | Solution | Intravenous | Either 8mg/kg or 10 mg/kg every 2 weeks | NA | Hemorrhage; Arterial Thromboembolic Events; Hypertension; Infusion-Related Reactions; Gastrointestinal Perforation; Impaired Wound Healing; Patients with Child-Pugh B or C Cirrhosis; Reversible Posterior Leukoencephalopathy Syndrome; Proteinuria Including Nephrotic Syndrome; Thyroid Dysfunction. | Link | NA | NA |
| 10845 | Th1208 | Metreleptin | >Th1208_Metreleptin MVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGLDFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLPWASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC | 16155.44 | C714H1167N191O221S6 | NA | NA | NA | 3.8 to 4.7 hours | Metreleptin, a recombinant analog of the human hormone leptin, is an orphan drug used to treat complications of leptin deficiency in people with congenital or acquired lipodystrophy. Affecting less than 500 people worldwide, lipodystrophy is characterized by a lack of adipose tissue, fat deposition in the muscles and liver, and metabolic complications such as hypertriglyceridemia, insulin resistance, diabetes mellitus, and fatty liver disease. These metabolic abnormalities are often aggravated by excessive food intake, which is further aggravated by leptin deficiency, a protein secreted by adipose tissue. Administration of Metreleptin results in improvement of metabolic symptoms including improvements in insulin resistance, reduced HbA1c and fasting glucose, reduced triglycerides, and reductions in food intake. Metreleptin is produced in E. coli and differs from native human leptin by the addition of a methionine residue at its amino terminus. It is administered as a once daily subcutaneous injection. On Feb. 24, 2014, Metreleptin was approved by the FDA for the treatment of complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy. Metreleptin is marketed under the brand Myalept® by Aegerion Pharmaceuticals, Inc. | It is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. | In patients with leptin deficiency, clinical trials demonstrated that exogenous leptin administration results in weight loss, reduction in mean HbA1c and fasting glucose levels, reduced blood insulin, and reduced triglyceride levels leading to improved insulin sensitivity and reductions in food intake. | Metreleptin functions by binding to and activating the human leptin receptor (ObR), which belongs to the Class I cytokine family of receptors that signals through the JAK/STAT transduction pathway. | The most common adverse events reported for metreleptin use have been headache, hypoglycemia, weight loss, and abdominal pain. A boxed warning states that anti-metreleptin antibodies, serious infections, and worsening metabolic control have been reported in patients taking the drug, and that some patients with acquired generalized lipodystrophy taking metreleptin have developed T-cell lymphoma. Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with metreleptin which can lead to inhibition of endogenous leptin action and loss of drug efficacy. As part of a Risk Evaluation and Mitigation Strategy (REMS), the FDA has required healthcare providers to be trained in the use of metreleptin before prescribing it and to attest that patients for whom they prescribe metreleptin have a labeled indication for the drug. Metreleptin is classified as category C (no adequate studies in women) for use during pregnancy. Two-year carcinogenicity studies in rodents have not been conducted with metreleptin. No proliferative or preneoplastic lesions were observed in mice or dogs following treatment up to six months. However, leptin is reported in the literature to promote cell proliferation in vitro and tumor progression in some mouse models of cancer. Metreleptin was not mutagenic in the Ames bacterial mutagenicity assay or clastogenic in an in vitro chromosomal aberration assay in Chinese hamster ovary cells and human peripheral blood lymphocytes. Metreleptin was not mutagenic or clastogenic in an in vivo mouse micronucleus assay. In a fertility study in mice, metreleptin had no adverse effects on mating, fertility, or early embryonic development at doses ranging between 7 and 15 times the maximum recommended clinical dose based on body surface area of a 20- and 60-kg patient, respectively. | No formal metabolism studies have been conducted with metreleptin. Nonclinical data indicate renal clearance is the major route of metreleptin elimination, with no apparent contribution of systemic metabolism or degradation. | Peak serum leptin concentration (Cmax) occurred approximately 4.0 to 4.3 hours after subcutaneous administration of single doses ranging from 0.1 to 0.3 mg/kg in healthy subjects. | Following intravenous administration of metreleptin, leptin volume of distribution was approximately 4 to 5 times plasma volume; volumes (mean ± SD) were 370 ± 184 mL/kg, 398 ± 92 mL/kg, and 463 ± 116 mL/kg for 0.3, 1.0, and 3.0 mg/kg/day doses, respectively. | The clearance of metreleptin is expected to be delayed in the presence of leptin antibodies. | Adipokines,Alimentary Tract and Metabolism,Amino Acids and Derivatives,Amino Acids, Peptides, and Proteins,Analogs/Derivatives,Biological Factors,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Intercellular Signaling Peptides and Proteins,Leptin Analog,Obesity, drug therapy,Peptide Hormones,Peptides,Proteins | US20070099836 | 29-11-2006 | 29-11-2026 | Chlorotrianisene, Chlorpropamide, Cyclosporine, Dienogest, Etonogestrel, Gliclazide, Glimepiride, Glipizide, Glyburide, Insulin Aspart, Insulin Degludec, Insulin Detemir, Insulin Glargine, Insulin Glulisine, Insulin Human, Insulin Lispro, Levonorgestrel, Medroxyprogesterone acetate, Norethisterone, Theophylline, Tolazamide, Tolbutamide, Warfarin | Leptin receptor | Myalept | Amylin Pharmaceuticals, LLC | Amylin Pharmaceuticals, LLC | MYALEPT (metreleptin) for injection is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. | NA | NA | Lyophilized powder for solution | subcutaneous | The starting daily dose (injection volume) should be 0.06 mg/kg for a baseline weight of less than 40kg. For a weight greater than 40 kg, the starting dose should be 2.5 mg (0.5 mL) for males and 5 mg (1 mL) for females. | MYALEPT is contraindicated in patients with general obesity not associated with congenital leptin deficiency. MYALEPT has not been shown to be effective in treating general obesity, and the development of anti-metreleptin antibodies with neutralizing activity has been reported in obese patients treated with MYALEPT; Also, is contraindicated in patients with prior severe hypersensitivity reactions to metreleptin or to any of the product components. Known hypersensitivity reactions have included urticaria and generalized rash. | As observed from an open-lable single-arm study the most frequesnt reactions were headache, hypoglycaemia, decreased weight, abdominal pain, athralgia, dizziness, ear infection, fatigue, nausea, ovarian cyst, upper respiratory tract infection, anaemia, diarrhea, back pain, paresthesia, proteinuria, pyrexia. | Link | NA | NA |
| 12574 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | von Willebrand factor | Cablivi | Sanofi Aventis | Sanofi Aventis | Intravenous; Subcutaneous | 11 mg / vial | CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of the excipients. Hypersensitivity reactions have included urticaria | nosebleed, headache, bleeding gums, fatigue, fever, injection site reactions (bleeding, itching), back pain, muscle pain, numbness and tingling, urinary tract infection (UTI), blood in the urine, abnormal vaginal bleeding, shortness of breath, and hives | Cablivi is used to treat acquired thrombotic thrombocytopenic purpura (aTTP) in adults. This medicine is given together with immunosuppressant medication and plasma exchange (transfusion). Cablivi may also be used for purposes not listed in this medication guide. Warnings Cablivi can increase your risk... | Cablivi is a prescription medicine used to treat the symptoms of Acquired Thrombotic Thrombocytopenia Purpura (aTTP). Cablivi may be used alone or with other medications. | NA | Caplacizumab-yhdp is a von Willebrand factor (vWF)-directed antibody fragment that consists of two identical humanized building blocks, linked by a three-alanine linker. Caplacizumab-yhdp is produced in Escherichia coli by recombinant DNA technology and has an approximate molecular weight of 28 kDa. | Link | Link | NA |
| 12575 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Antibodies, Monoclonal | NA | NA | NA | NA | von Willebrand factor | Cablivi | Ablynx Nv | Ablynx Nv | Intravenous; Subcutaneous | 10 mg | CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of the excipients. Hypersensitivity reactions have included urticaria | nosebleed, headache, bleeding gums, fatigue, fever, injection site reactions (bleeding, itching), back pain, muscle pain, numbness and tingling, urinary tract infection (UTI), blood in the urine, abnormal vaginal bleeding, shortness of breath, and hives | Cablivi is used to treat acquired thrombotic thrombocytopenic purpura (aTTP) in adults. This medicine is given together with immunosuppressant medication and plasma exchange (transfusion). Cablivi may also be used for purposes not listed in this medication guide. Warnings Cablivi can increase your risk... | Cablivi is a prescription medicine used to treat the symptoms of Acquired Thrombotic Thrombocytopenia Purpura (aTTP). Cablivi may be used alone or with other medications. | NA | Caplacizumab-yhdp is a von Willebrand factor (vWF)-directed antibody fragment that consists of two identical humanized building blocks, linked by a three-alanine linker. Caplacizumab-yhdp is produced in Escherichia coli by recombinant DNA technology and has an approximate molecular weight of 28 kDa. | Link | Link | NA |
| 12576 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Antibodies, Monoclonal, Humanized | NA | NA | NA | NA | von Willebrand factor | Cablivi | Genzyme Corporation | Genzyme Corporation | Intravenous; Subcutaneous | 11 mg/1mL | CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of the excipients. Hypersensitivity reactions have included urticaria | nosebleed, headache, bleeding gums, fatigue, fever, injection site reactions (bleeding, itching), back pain, muscle pain, numbness and tingling, urinary tract infection (UTI), blood in the urine, abnormal vaginal bleeding, shortness of breath, and hives | Cablivi is used to treat acquired thrombotic thrombocytopenic purpura (aTTP) in adults. This medicine is given together with immunosuppressant medication and plasma exchange (transfusion). Cablivi may also be used for purposes not listed in this medication guide. Warnings Cablivi can increase your risk... | Cablivi is a prescription medicine used to treat the symptoms of Acquired Thrombotic Thrombocytopenia Purpura (aTTP). Cablivi may be used alone or with other medications. | NA | Caplacizumab-yhdp is a von Willebrand factor (vWF)-directed antibody fragment that consists of two identical humanized building blocks, linked by a three-alanine linker. Caplacizumab-yhdp is produced in Escherichia coli by recombinant DNA technology and has an approximate molecular weight of 28 kDa. | Link | Link | NA |
| 12577 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Antiplatelet agents | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12578 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Antithrombotic Agents, Misc. | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12579 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Blood and Blood Forming Organs | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12580 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Blood Proteins | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12581 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Globulins | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12582 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Immunoglobulin Fab Fragments | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12583 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Immunoglobulin Fragments | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12584 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Immunoglobulin Variable Region | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12585 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Immunoglobulins | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12586 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Immunoproteins | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12587 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Peptide Fragments | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12588 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Peptides | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12589 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Proteins | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12590 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | Serum Globulins | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 12591 | Th1335 | Caplacizumab | >Th1335_Caplacizumab EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQGTQVTVSS | 27880 | C1213H1891N357O380S10 | 6.6 - 7.2 | NA | 61 ºC (Fab fragment) | The reported half-life is reported to be in the range of 16-27 hours.[F3457] | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,[L5302] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[A174634] | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[A174634, L5302] aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[A174649] Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[A174634] | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[A174634] In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[A174634] as well as a significant reduction in the median time to response of about 39%.[A174652] However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[A174643] The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[L5302] | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[A174634] | Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label] To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity | Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours[A174634] and it presents a very high bioavailability reaching approximately 90%.[F3457] The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.[L5314] | The reported volume of distribution of caplacizumab is 6.33 L.[A174634] | As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. | von Willebrand Factor, antagonists & inhibitors | NA | NA | NA | NA | von Willebrand factor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13161 | Th1389 | Human cord blood hematopoietic progenitor cell | NA | NA | NA | NA | NA | NA | Pharmacokinetic parameters do not apply for human cord blood hematopoietic progenitor cells. | Human cord blood hematopoietic progenitor cells consist of hematopoietic progenitor cells, monocytes, lymphocytes, and granulocytes from human cord blood. They are used during allogeneic unrelated and related hematopoietic stem cell transplantation procedures in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment. Human umbilical cord is a rich source of hematopoietic stem cells and progenitor cells that are capable of proliferation _in vitro_. Active and viable hematopoietic progenitor cells, or hematopoietic stem cells (HSCs) express the cell surface marker CD34 which is critical for cell identification [A32216]. Upon division and maturation at the bone marrow following intravenous administration to the patient, hematopoietic progenitor cells enter the systemic circulation to restore blood counts and function [FDA Label]. After the first cord blood transplant in 1988 in a patient with Fanconi anemia [A32220], the use of umbilical cord blood transplantation was increased in clinical settings. Human cord blood hematopoietic progenitor cells can be collected from both related or unrelated donors. The unrelated donor transplant setting has several advantages over related donor transplant and bone marrow transplantation; it allows shorter time to transplant and tolerance of 1–2 human leukocyte antigen mismatch due to expanded donor pool, which increases the chance of finding a suitable donor, particularly in patients requiring urgent transplantation [A32219]. Other advantages of HSC transplantation include a lower risk of transmitting infections by latent viruses and improved targeting of ethnic minorities increased pool of rare haplotypes [A32219]. Umbilical cord blood cell transplantation was also associated with reduced incidence and severity of graft versus host disease (GVHD) thus improved survival rates of transplant patients compared to allogeneic bone marrow transplant setting, which may be due to "naive" nature of lymphocytes [A32223]. Hemacord is marketed in the U.S. as an allogeneic cord blood hematopoietic progenitor cell therapy for intravenous use. | Indicated for use in unrelated donor hematopoietic progenitor cell transplantation procedures in conjunction with an appropriate preparative regimen for hematopoietic and immunologic reconstitution in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment [FDA Label]. | Human cord blood hematopoietic progenitor cells constitute the hematopoietic progenitor cells, monocytes, lymphocytes, and granulocytes that are isolated from red blood cells and plasma volume that are collected from the human umbilical cord and placenta [FDA Label]. According to the findings of retrospective data reviews and a single-arm prospective study, patients with hematologic malignancy who are receiving human cord blood hematopoietic progenitor cell transplantation achieved recovery of neutrophil counts, platelet counts, erythrocyte counts at rates of 76-83 %, 57-77 %, and 46-77 %, respectively [FDA Label]. | Upon collection, the blood from human umbilical cord or placenta volume reduced and partially depleted of red blood cells and plasma. The remaining cells consist of hematopoietic progenitor cells (HPCs), monocytes, lymphocytes, and granulocytes. HPCs express the CD34 surface antigen; this allows distinct identification and characterization of those cells. With the evidence of CD34+ cells being able to engraft, CD34+ cells have been selected and widely used both for human autologous and allogeneic transplantations [A32216]. Human cord blood HPCs, that are intravenously administered, travel to the bone marrow of the transplant recipient where they undergo cell division and maturation. Mature cells are then released from the bone marrow where they enter the systemic bloodstream to circulate and travel to tissue sites. Mature cells serve to partially or fully restore hematologic function in patients with hematologic disorders by improving the counts and function of blood-borne cell, including immune cells, that originate from the bone marrow [FDA Label]. It is also suggested that mature leukocytes from HPC transplantation may synthesize enzymes that are able to circulate and improve cellular functions of some native tissues in patients with enzymatic abnormalities arising from types of storage disorders. Clear mechanism of this effect is not fully elucidated [FDA Label]. | There has been no cases of overdose with human cord blood hematopoietic progenitor cell therapy, and single doses up to 57.6 x 107 TNC/kg have been administered. Higher doses of dimethyl sulfoxide (DMSO) in the infusion mixture may induce altered mental status and coma. For DMSO overdosage, general supportive care is recommended [FDA Label]. | Pharmacokinetic parameters do not apply for human cord blood hematopoietic progenitor cells. | Intravenous administration achieves complete bioavailability. | Pharmacokinetic parameters do not apply for human cord blood hematopoietic progenitor cells. | Pharmacokinetic parameters do not apply for human cord blood hematopoietic progenitor cells. | Allogeneic Cord Blood Hematopoietic Progenitor Cell Therapy | NA | NA | NA | NA | NA | HemaCord | New York Blood Center | New York Blood Center | Intravenous | 500000000 1/25mL | None | high blood pressure (hypertension), vomiting, nausea, show heart rate, and fever | NA | HemaCord is a prescription medicine used for Stem Cell Transplantation. HemaCord may be used alone or with other medications. | NA | HEMACORD consists of hematopoietic progenitor cells, monocytes, lymphocytes, and granulocytes from human cord blood for intravenous infusion. Blood recovered from umbilical cord and placenta is volume reduced and partially depleted of red blood cells and plasma. | Link | Link | NA |
| 13361 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | Recothrom | The Medicines Company | The Medicines Company | Topical | 1000 [iU]/1mL | Do not inject directly into the circulatory system. Do not use for the treatment of massive or brisk arterial bleeding. Do not administer to patients with a history of hypersensitivity to RECOTHROM or any components of RECOTHROM. Do not use in patients with known hypersensitivity to hamster proteins. | blood clots detaching from their point of origin and moving through the bloodstream (thromboembolic events), and antibody formation. | RECOTHROM, Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. | RECOTHROM®, Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age. | NA | NA | Link | Link | NA |
| 13362 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Biological Factors | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | Recothrom | Zymo Genetics | Zymo Genetics | Topical | 1000 [iU]/1mL | Do not inject directly into the circulatory system. Do not use for the treatment of massive or brisk arterial bleeding. Do not administer to patients with a history of hypersensitivity to RECOTHROM or any components of RECOTHROM. Do not use in patients with known hypersensitivity to hamster proteins. | blood clots detaching from their point of origin and moving through the bloodstream (thromboembolic events), and antibody formation. | RECOTHROM, Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. | RECOTHROM®, Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age. | NA | NA | Link | Link | NA |
| 13363 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Blood Coagulation Factors | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | Recothrom | Baxter Healthcare Corporation | Baxter Healthcare Corporation | Topical | 1000 [iU]/1mL | Do not inject directly into the circulatory system. Do not use for the treatment of massive or brisk arterial bleeding. Do not administer to patients with a history of hypersensitivity to RECOTHROM or any components of RECOTHROM. Do not use in patients with known hypersensitivity to hamster proteins. | blood clots detaching from their point of origin and moving through the bloodstream (thromboembolic events), and antibody formation. | RECOTHROM, Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. | RECOTHROM®, Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age. | NA | NA | Link | Link | NA |
| 13364 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Blood Proteins | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | Recothrom | Mallinckrodt Hospital Products Inc. | Mallinckrodt Hospital Products Inc. | Topical | 1000 [iU]/1mL | Do not inject directly into the circulatory system. Do not use for the treatment of massive or brisk arterial bleeding. Do not administer to patients with a history of hypersensitivity to RECOTHROM or any components of RECOTHROM. Do not use in patients with known hypersensitivity to hamster proteins. | blood clots detaching from their point of origin and moving through the bloodstream (thromboembolic events), and antibody formation. | RECOTHROM, Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. | RECOTHROM®, Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age. | NA | NA | Link | Link | NA |
| 13365 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Endopeptidases | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | Recothrom | Baxter Laboratories | Baxter Laboratories | Topical | 24000 unit / vial | Do not inject directly into the circulatory system. Do not use for the treatment of massive or brisk arterial bleeding. Do not administer to patients with a history of hypersensitivity to RECOTHROM or any components of RECOTHROM. Do not use in patients with known hypersensitivity to hamster proteins. | blood clots detaching from their point of origin and moving through the bloodstream (thromboembolic events), and antibody formation. | RECOTHROM, Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. | RECOTHROM®, Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age. | NA | NA | Link | Link | NA |
| 13366 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Enzymes | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | Recothrom | Baxter Laboratories | Baxter Laboratories | Topical | 6000 unit / vial | Do not inject directly into the circulatory system. Do not use for the treatment of massive or brisk arterial bleeding. Do not administer to patients with a history of hypersensitivity to RECOTHROM or any components of RECOTHROM. Do not use in patients with known hypersensitivity to hamster proteins. | blood clots detaching from their point of origin and moving through the bloodstream (thromboembolic events), and antibody formation. | RECOTHROM, Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. | RECOTHROM®, Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age. | NA | NA | Link | Link | NA |
| 13367 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Enzymes and Coenzymes | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13368 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Hemorrhage | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13369 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Hemostatics | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13370 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Hydrolases | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13371 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Increased Coagulation Factor Activity | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13372 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Peptide Hydrolases | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13373 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Proteins | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13374 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Serine Endopeptidases | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13375 | Th1398 | Thrombin alfa | >Th1398_Thrombin_alfa MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE | NA | NA | NA | NA | NA | Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) [L2079]. Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours [L2079]. This data follows administration of thrombin alfa to cynomolgus monkeys. | Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 [L2079]. Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency [L2079]. | Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age [FDA Label]. Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP [FDA Label]. | As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor [L2079]. In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa [A32408]. Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot [A32408]. Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets [A32408]. | Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding [FDA Label]. In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability [FDA Label, L2079]. The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Data regarding overdosage are not available. The predominant adverse reaction associated with thrombin alfa is the possibility of thrombosis or other thromboembolic events occurring [FDA Label]. | Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long [FDA Label]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [FDA Label, L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [FDA Label, L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys [L2079]. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Volume of distribution data is subsequently not readily available. | Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa [L2079]. Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079]. | Serine Proteases | NA | NA | NA | NA | Coagulation factor V,Coagulation factor VIII,Fibrinogen alpha chain,Fibrinogen beta chain,Fibrinogen gamma chain | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13447 | Th1404 | Tasonermin | >Th1404_Tasonermin VRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELRDNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL | 17724 | NA | 6.7 | NA | NA | Tasonermin has a terminal half life of 20-30 min at doses of 150 µg/m² [L1339]. This value increases as dosage increases. | Tasonermin is recombinant soluble form tumor necrosis factor α produced via _Escherichia coli_ cell culture. It was approved for use by the European Medicines Agency in April of 1999 for use as an adjunt to surgery for the subsequent removal of the tumor and in palliative care for irresectable soft tissue sarcoma of the limbs as the product Beromun. It is administered with [DB01042] via mild hyperthermic isolated limb perfusion. | For use in adults as an adjunct to surgery for subsequent removal of the tumour so as to prevent or delay amputation, or in palliative care, for irresectable soft tissue sarcoma of the limbs [FDA Label]. Used in combination with melphalan via mild hyperthermic isolated limb perfusion. | Tasonermin is thought to contribute to the destruction of tumor tissue via several direct and indirect effects [FDA Label]. Tasonermin directly inhibits cell proliferation in a variety of cancer cells. It also modifies endothelial cell morphology and reduces their proliferation in tumor microvasculature. Modification of the expression of cell adhesion proteins, proteins affecting coagulation, interleukins, and hematopoietic growth factors favors a procoagulant state resulting in microvascular thrombosis. These changes also increase infiltration of the tumor tissue by leukocytes. Monocytes, macrophages, and granulocytes are activated allowing better adherence to the endothelium and subjecting the tumor cells to phagocytosis and respiratory bursts as well as producing degranulation of immune cells to further enhance inflammatory activity. Active antigen presenting cells are able to activate and induce proliferation of T- and B-lymphocyte cells to allow the adaptive immune system to contribute to tumor cell damage. These changes lead to hemorraghic necrosis of the tumor. | Since tasonermin is recombinant TNF-α, it functions exactly as endogenous TNF-α does. The direct cytotoxic effect of TNF-α is mediated by TNF-α receptor 1 [A31954]. The bound receptor activates the well-reviewed death receptor pathway involving the activation of initiator caspases 8 and 9 then ultimately ending in the activation of effector caspase 3 which begins the process of apoptosis. The effect on tumor vasculature is mediated by the inflammatory signalling pathway of TNF-α, the NFκB pathway [A31954]. This pathway is also activated by TNFR1 when bound to TNFα. The NFκB transcription factor increases expression of proteins in vascular endothelial cells. These proteins include cell adhesion molecules, inflammatory mediators like prostaglandins and interleukins, and growth factors [A31958]. TNF-&alpha also increases the expression of inducible nitric oxide synthase via this pathway which contributes to the generation of reactive nitrogen species [A31956]. These species are able to damage cells in the tumor and microvasculature. The cytokines produced from NFκB activation and TNF-&aplha; itself serve to activate the cells of the immune system which further damage tumor cells with respiratory bursts, phagocytosis and subsequent breakdown of the cell, and release of cytotoxic enzymes. The antigen presenting cells which phagocytose the tumor cells are able to activate lymphocytes and allow the adaptive immune system to further damage the tumor tissue [T116]. | In addition to its intended cytotoxic effects, tasonermin produces secondary adverse effects. Studies in mice, rats, dogs, monkeys, and rabbits observed hematological changes including anemia, increased hematocrit, and changes in leukocyte and platelet counts dependent on species and treatment duration [FDA Label]. Tasonermin also produces decreases in blood pressure. Increases in heart rate and reductions in cardiac contractility have been noted in some studies. Increased liver enzymes suggest altered liver function as a result of tasonermin administration. Changes in kidney function have also been observed including increased water and sodium excretion as well as increased serum urea and creatinine. The only study to determine a no observable adverse effect level found the value to be 0.1 µg/kg in monkeys during a 7-day course of tasonermin. | No metabolism data is available. Tasonermin is assumed to be broken down similarly to other proteins in systemic circulation. | No absorption data is available. No enteral route formulation exists for tasonermin. | The estimated volume of distribution varies with the dose administered with intravenous doses of 35 µg/m² and 150 µg/m² producing values of 55 L and 17 L respectively [L1339]. | Clearance was estimated to be 2 L/min and 0.5 L/min after intravenous doses of 35 µg/m² and 150 µg/m² respectively [L1339]. This value decreases as dosage increases. | Adjuvants, Immunologic | NA | NA | NA | NA | Tumor necrosis factor receptor superfamily member 1A,Tumor necrosis factor receptor superfamily member 1B | Beromun | Belpharma S.A. | Belpharma S.A. | NA | 1 mg/5ml | NA | Most patients taking Beromun experience fever, which is usually mild to moderate. Other side effects seen very commonly (in more than 1 patient in 10) are infection, cardiac arrhythmia (unstable heartbeat), nausea (feeling sick), vomiting, liver damage, fatigue (tiredness), chills, pain in the limb, nerve injury, skin reactions, oedema (swelling) and wound infection. Some side effects of Beromun are serious and could require a patient to spend time in an intensive-care unit after treatment. | Beromun is a powder and solvent that are made up into a solution for infusion. It contains the active substance tasonermin. | Beromun is used in patients with soft-tissue sarcoma (a type of cancer) of the limb (arm or leg), together with melphalan (an anticancer medicine), using a technique called ‘isolated-limb perfusion’ (ILP): both medicines are injected into the limb while the blood circulation in the limb is kept isolated (cut off) from the rest of the body. It can be used before surgery to reduce the size of a tumour, or instead of surgery when the tumour cannot be removed by surgery alone. | NA | NA | Link | Link | NA |
| 13448 | Th1404 | Tasonermin | >Th1404_Tasonermin VRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELRDNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL | 17724 | NA | 6.7 | NA | NA | Tasonermin has a terminal half life of 20-30 min at doses of 150 µg/m² [L1339]. This value increases as dosage increases. | Tasonermin is recombinant soluble form tumor necrosis factor α produced via _Escherichia coli_ cell culture. It was approved for use by the European Medicines Agency in April of 1999 for use as an adjunt to surgery for the subsequent removal of the tumor and in palliative care for irresectable soft tissue sarcoma of the limbs as the product Beromun. It is administered with [DB01042] via mild hyperthermic isolated limb perfusion. | For use in adults as an adjunct to surgery for subsequent removal of the tumour so as to prevent or delay amputation, or in palliative care, for irresectable soft tissue sarcoma of the limbs [FDA Label]. Used in combination with melphalan via mild hyperthermic isolated limb perfusion. | Tasonermin is thought to contribute to the destruction of tumor tissue via several direct and indirect effects [FDA Label]. Tasonermin directly inhibits cell proliferation in a variety of cancer cells. It also modifies endothelial cell morphology and reduces their proliferation in tumor microvasculature. Modification of the expression of cell adhesion proteins, proteins affecting coagulation, interleukins, and hematopoietic growth factors favors a procoagulant state resulting in microvascular thrombosis. These changes also increase infiltration of the tumor tissue by leukocytes. Monocytes, macrophages, and granulocytes are activated allowing better adherence to the endothelium and subjecting the tumor cells to phagocytosis and respiratory bursts as well as producing degranulation of immune cells to further enhance inflammatory activity. Active antigen presenting cells are able to activate and induce proliferation of T- and B-lymphocyte cells to allow the adaptive immune system to contribute to tumor cell damage. These changes lead to hemorraghic necrosis of the tumor. | Since tasonermin is recombinant TNF-α, it functions exactly as endogenous TNF-α does. The direct cytotoxic effect of TNF-α is mediated by TNF-α receptor 1 [A31954]. The bound receptor activates the well-reviewed death receptor pathway involving the activation of initiator caspases 8 and 9 then ultimately ending in the activation of effector caspase 3 which begins the process of apoptosis. The effect on tumor vasculature is mediated by the inflammatory signalling pathway of TNF-α, the NFκB pathway [A31954]. This pathway is also activated by TNFR1 when bound to TNFα. The NFκB transcription factor increases expression of proteins in vascular endothelial cells. These proteins include cell adhesion molecules, inflammatory mediators like prostaglandins and interleukins, and growth factors [A31958]. TNF-&alpha also increases the expression of inducible nitric oxide synthase via this pathway which contributes to the generation of reactive nitrogen species [A31956]. These species are able to damage cells in the tumor and microvasculature. The cytokines produced from NFκB activation and TNF-&aplha; itself serve to activate the cells of the immune system which further damage tumor cells with respiratory bursts, phagocytosis and subsequent breakdown of the cell, and release of cytotoxic enzymes. The antigen presenting cells which phagocytose the tumor cells are able to activate lymphocytes and allow the adaptive immune system to further damage the tumor tissue [T116]. | In addition to its intended cytotoxic effects, tasonermin produces secondary adverse effects. Studies in mice, rats, dogs, monkeys, and rabbits observed hematological changes including anemia, increased hematocrit, and changes in leukocyte and platelet counts dependent on species and treatment duration [FDA Label]. Tasonermin also produces decreases in blood pressure. Increases in heart rate and reductions in cardiac contractility have been noted in some studies. Increased liver enzymes suggest altered liver function as a result of tasonermin administration. Changes in kidney function have also been observed including increased water and sodium excretion as well as increased serum urea and creatinine. The only study to determine a no observable adverse effect level found the value to be 0.1 µg/kg in monkeys during a 7-day course of tasonermin. | No metabolism data is available. Tasonermin is assumed to be broken down similarly to other proteins in systemic circulation. | No absorption data is available. No enteral route formulation exists for tasonermin. | The estimated volume of distribution varies with the dose administered with intravenous doses of 35 µg/m² and 150 µg/m² producing values of 55 L and 17 L respectively [L1339]. | Clearance was estimated to be 2 L/min and 0.5 L/min after intravenous doses of 35 µg/m² and 150 µg/m² respectively [L1339]. This value decreases as dosage increases. | Antineoplastic and Immunomodulating Agents | NA | NA | NA | NA | Tumor necrosis factor receptor superfamily member 1A,Tumor necrosis factor receptor superfamily member 1B | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13459 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | Inductos | Medtronic Bio Pharma B.V. | Medtronic Bio Pharma B.V. | NA | 1.5 mg/ml | NA | The most common side effects with Inductos (seen in more than 1 patient in 10) are radiculopathic events (problems occurring at or near the root of the nerve, along the spine, resulting in pain, weakness, numbness, or difficulty controlling specific muscles) when used in spine surgery, and localised infection when used in tibia fracture surgery. The most severe side effect is localised oedema (swelling at the surgery site) when used in upper spine (neck) surgery. | Inductos is a kit for implant. The kit consists of a powder containing the active substance, dibotermin alfa, a solvent and a matrix (collagen sponge). | Inductos is used to help new bone develop. | NA | NA | Link | Link | NA |
| 13460 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Biological Factors | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13461 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Bone Morphogenetic Proteins | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13462 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Drugs Affecting Bone Structure and Mineralization | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13463 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Drugs for Treatment of Bone Diseases | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13464 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Intercellular Signaling Peptides and Proteins | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13465 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Musculo-Skeletal System | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13466 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Peptides | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13467 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Proteins | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13468 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | TGF-beta Superfamily Proteins | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15359 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Carcinoembryonic antigen | Scintimun | Cis Bio International | Cis Bio International | Intravenous | 1 mg | NA | The most common side effect with Scintimun (seen in more than 1 patient in 10) is the production of anti-mouse antibodies. | Scintimun is a kit for the preparation of a radioactive solution for injection. It contains the active substance besilesomab. | It is used to locate areas of infection or inflammation in adults with suspected osteomyelitis (bone infection) in the limbs, in combination with other appropriate imaging methods. | NA | NA | Link | Link | NA |
| 15360 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Antibodies | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15361 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Antibodies, Monoclonal | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15362 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Blood Proteins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15363 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Globulins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15364 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Immunoglobulins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15365 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Immunoproteins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15366 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Proteins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15367 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Radiopharmaceuticals | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15368 | Th1591 | Besilesomab | NA | NA | NA | NA | NA | NA | Whole blood concentration-time radioactivity curves show a two-phase course, which can be subdivided into an early phase (0-2 h) and a late phase (5-24 h) [FDA Label]. After correcting for the decay of radionuclide, the calculated half-life of the early phase is approximately 0.5 h while the late phase demonstrates a calculated half-life of 16 h [FDA Label]. The terminal half-life in man is estimated to be approximately 23 h [L1623]. | Besilesomab is a mouse monoclonal antibody labelled with the radioactive isotope technetium-99m for determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. Utilised only as a diagnostic agent, besilesomab is currently approved by the EMEA for marketing and use in various European countries like Italy, France, Germany, Spain, Portugal, Norway, Sweden, the Netherlands, and the United Kingdom [L1564]. | Besilesomab is radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution. This solution is indicated in adults for scintigraphic imaging - in conjunction with other appropriate imaging modalities, when possible - in determining the location of inflammation/infection in peripheral bone in adults with suspected osteomyelitis [FDA Label]. When utilized as such, this medicinal product is for diagnostic use only [FDA Label]. | In a study employing cryo-preserved human tissues using an indirect alkaline phosphatase anti-alkaline phosphatase technique, besilesomab antibody from hybridoma supernatants demonstrated staining to cytoplasmic, membranous, and interstitial areas of primary colon carcinoma tissue, to single granulocytic cells in normal human liver and lung and to a large proportion of granulocytic cells in normal human bone marrow but not to blood vessels or connective tissue [L1623]. Additionally, the antibody also shows binding to the granulocytic cells of breast, kidney, parotid gland, pituitary, lymph nodes, and spleen tissues, as well as colonic, pancreatic, and some lung and breast carcinomas [L1623]. The purified besilesomab antibody and the prepared kit subsequently bound similarly to granulocytes in normal bone marrow, lung, liver, spleen, and colorectal carcinomas. Furthermore, the prepared kit also produced some staining in some connective tissue fibres in normal lung, some muscle fibres in normal colon, and in liver parenchymal cells [L1623]. In general however, besilesomab does not bind significantly to blood vessels and connective tissue [L1623]. | Nonspecific cross-reacting antigens (NCA) is the name of a collection of highly glycosylated bacterial binding receptors expressed on human granulocytes and other tissues [A32084]. In particular, these glycoprotein receptors are members of the immunoglobulin supergene family and are related structurally to carcinoembryonic antigen (CEA) [A32084]. CEA is found naturally in the human body and its expression may be increased in both cancer and non-cancerous (benign) circumstances. Besilesomab is subsequently a murine immunoglobulin monoclonal antibody of IgG1 isotype designed to recognise and bind specifically to NCA-95, or nonspecific cross-reacting antigen 95, an epitope found expressed on the cell membranes of granulocytes and granulocyte precursors [FDA Label]. When radiolabelled with sodium pertechnetate (Tc99m) solution to develop technetium (Tc99m) besilesomab solution, this radiolabelled medicine is injected into patients where the monoclonal antibody carries it to target CEA on target granulocytes [FDA Label]. When large numbers of CEA expressing granulocytes gather to the site of an infection, the radioactive monoclonal antibodies will also accumulate at such sites, where it can be detected by diagnostic scanning [FDA Label]. The resultant images show where the radioactive besilesomab has accumulated, locating areas affected by osteomyelitis, infection, or inflammation [FDA Label]. Furthermore, it is believed that the besilesomab accumulation is predominantly passive (via increased vascular permeability) and only partially active (via migration of human granulocytes carrying besilesomab to the infection/inflammation location) since only 10% to 20% of the injected radio-diagnostic agent binds in vivo to human circulating granulocytes [L1623]. Specific binding of besilesomab to activated granulocytes that have already migrated to sites of infection/inflammation might be the primary part of the detection signal [L1623]. | The most commonly reported adverse reaction associated with the use of besilesomab is the development of Human Anti-Mouse Antibodies (HAMA) after a single administration [FDA Label]. Patients who have developed HAMA may potentially have a higher risk for hypersensitivity reactions. Screening for possible previous exposure to murine monoclonal antibodies and tests for the presence of HAMA in prospective patients should be made prior to administrating besilesomab [FDA Label]. Moreover, because the incidence of developing HAMA appears to be dose related with besilesomab, the recommended dosage is restricted to no more than 250 micrograms of antibody per injection [T132]. Patients who are HAMA positive are consequently contraindicated from using besilesomab [FDA Label]. Hypersensitivity to besilesomab or to any other murine antibodies or to any of the excipients associated with the active besilesomab radio-diagnostic agent is subsequently a contraindication [FDA Label]. Some patients have also reported hypotension as a common adverse reaction [FDA Label]. As exposure to ionizing radiation is linked with cancer induction and a potential for developing hereditary defects, the use of radio-diagnostic besilesomab in pregnant women is considered a formal contraindication [FDA Label]. If in doubt about a woman's potential pregnancy, alternative techniques to not using ionizing radiation should be considered and/or offered instead to the patient [FDA Label]. Moreover, although it is not known if besilesomab is excreted in human milk, the potential risk to a breast-fed child cannot be excluded [FDA Label]. Furthermore, while consideration should be given to the possibility of perhaps delaying the administration of radionuclide agents until the mother has ceased breastfeeding or perhaps certainly choosing alternative radoopharmaceuticals with more appropriate secretion activity, if the use of besilesomab is absolutely necessary then the mother's breastfeeding should be stopped for three days and any expressed feeds during that time discarded [FDA Label]. The time period of three days corresponds to 10 half-lives of technetium (Tc99m)(60 hours) [FDA Label]. At that time, the remaining activity represents about 1/1000 of the initial activity in the body [FDA Label]. In general, close contact with infants and pregnant women should be restricted for patients who have been administered besilesomab during the first 12 hours after the injection [FDA Label]. Since besilesomab contains sorbitol, patients having any rare hereditary conditions of fructose intolerance should not be administered this medicine [FDA Label]. Because no sufficient data regarding the safety and efficacy of using besilesomab in children below the age of 18 years exists, the use of besilesomab in this patient population is not recommended [L1711]. Even though data regarding the repeated dosing of besilesomab is extremely limited, the use of besilesomab should only be used once in a patient's lifetime [FDA Label]. Other medicines that can inhibit inflammation or affect the hematopoietic system (like antibiotics and corticosteroids) can lead to false negative results. Such agents should therefore not be administered together with, or a short time before the injection of besilesomab [FDA Label]. Preclinical data obtained with the non-radioactive compound revealed no special hazard for humans based on conventional studies of safety pharmacology, single-dose and repeated dose toxicity, although antimurine antibodies were found in all dose groups (including controls) in a repeated-dose study in monkeys [FDA Label]. Genotoxicity studies conducted to test for potentially genotoxic impurities were also negative. Long-term carcinogenicity studies and toxicity to reproduction have not yet been carried out [FDA Label]. | The besilesomab antibody is mainly metabolized via hepatic clearance into amino acids [L1623]. Nevertheless, liver uptake of radioactivity was observed to be minimal under trial conditions and liver impairment is considered unlikely to affect besilesomab metabolism and elimination in any clinically significant manner [L1623]. The total blood radioactivity occurring from the administration of besilesomab is generally the result of the contribution of radioactive intact labelled antibody and other radioactive moieties like metabolized antibody fragments, smaller radiometabolites, and free technetium (Tc99m) [L1623]. | As the diagnostic agent is administered intravenously, it is expected that the bioavailability is 100% [L1623]. Approximately six hours after injection, about 1.5% of the whole body radioactivity is detected in the liver while about 3.0% is found in the spleen [FDA Label]. Observations twenty-four hours after injection demonstrate percentages of radioactivity of 1.6% in the liver and 2.3% in the spleen [FDA Label]. However, non pathological, unusual accumulations of the radioactive agent can be detected in the spleen (up to 6% of patients), in the bowel (up to 4% of patients), in the liver and bone marrow (up to 3% of patients), and in the thyroid and kidneys (up to 2% of patients) [FDA Label]. | In the besilesomab clinical trial Study 7D-101SZ-A, volumes of distribution were determined as approximately 4L - which was close to the plasma volume - in the central compartment, whether calculated from plasma radioactivity or from intact monoclonal antibody concentrations; the peripheral compartment was somewhat greater, at about 6L for both methods [L1623]. | Once administered into the body, prepared technetium (Tc99m) besilesomab can be metabolized into free amino acids, smaller radioactive fragments, or even free pertechnetate (Tc99m) [L1623]. The besilesomab clinical study 7D-101SZ-A consequently reports separate estimated clearance rates of 0.322 L/h and 0.242 L/h that were calculated using monitored plasma radioactivity and from monitored intact monoclonal antibody concentrations, respectively [L1623]. | Serum Globulins | NA | NA | NA | NA | Carcinoembryonic antigen | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15799 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Angiopoietin-related protein 3 | Evkeeza | Regeneron Pharmaceuticals, Inc. | Regeneron Pharmaceuticals, Inc. | Intravenous | 150 mg/1mL | EVKEEZA is contraindicated in patients with a history of serious hypersensitivity reaction to evinacumab-dgnb or to any of the excipients in EVKEEZA. Serious hypersensitivity reactions, including anaphylaxis, have occurred [see WARNINGS AND PRECAUTIONS]. | common cold, • influenza-like illness, • dizziness, • runny nose, and • nausea | Evkeeza is an injectable prescription medicine used along with other low-density lipoprotein (LDL) lowering medicines in people older than 12 years of age with a type of high cholesterol called homozygous familial hypercholesterolemia (HoFH). It is not known if this medicine is safe and effective in... | EVKEEZA is indicated as an adjunct to other low-density lipoprotein-cholesterol (LDL-C) lowering therapies for the treatment of adult and pediatric patients, aged 12 years and older, with homozygous familial hypercholesterolemia (HoFH). | NA | These are not all of the possible side effects of EVKEEZA. | Link | Link | NA |
| 15800 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Angiopoietin-like 3 Inhibitor | NA | NA | NA | NA | Angiopoietin-related protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15801 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Angiopoietin-like 3 Inhibitors | NA | NA | NA | NA | Angiopoietin-related protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15802 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Antibodies | NA | NA | NA | NA | Angiopoietin-related protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15803 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Globulins | NA | NA | NA | NA | Angiopoietin-related protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15804 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Hypolipidemic Agents | NA | NA | NA | NA | Angiopoietin-related protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15805 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Immunoproteins | NA | NA | NA | NA | Angiopoietin-related protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15806 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Lipid Regulating Agents | NA | NA | NA | NA | Angiopoietin-related protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15807 | Th1630 | Evinacumab | >Th1630_Evinacumab EVQLVESGGGVIQPGGSLRLSCAASGFTFDDYAMNWVRQGPGKGLEWVSAISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAFFYCAKDLRNTIFGVVIPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | 146000 | NA | NA | NA | NA | The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable.[L31833] This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.[L31833] | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years.[A229273] Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.[A229278] In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza".[L31838] Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.[L31833] | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol.[L31833] It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.[L31833] Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose.[L31833] | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk.[A229273,A229318] While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders,[A229273] ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy.[A229318] ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.[L31833] Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.[L31833] | There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness.[L31833] Patients experiencing an overdose should be treated with symptomatic and supportive measures. | The biotransformation of evinacumab has not been characterized.[L31833] Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids.[A216712] | Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the Cmax at the end of infusion is approximately 689 mg/L.[L31833] | The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.[L31833] | NA | Proteins | NA | NA | NA | NA | Angiopoietin-related protein 3 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 16384 | Th1894 | Tirzepatide | >Th1894_Tirzepatide YXEGTFTSDYSIXLDKIAQKAFVQWLIAGGPSSGAPPPS | 4810.52 Da | C225H348N48O68 | NA | NA | NA | ,The half-life is approximately five days. | Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Dual GIP/GLP-1 agonists gained increasing attention as new therapeutic agents for glycemic and weight control as they demonstrated better glucose control and weight loss compared to selective GLP-1 receptor agonists in preclinical and clinical trials. | Tirzepatide is a dual GIP and GLP-1 receptor agonist used for the treatment of type II diabetes in adults as an adjunct to diet and exercise. | Tirzepatide is a synthetic peptide with glucose-lowering effects. It works to stimulate first- and second-phase insulin secretion, and reduces glucagon levels, both in a glucose-dependent manner. Tirzepatide was also shown to delay gastric emptying, lower fasting and postprandial glucose concentration, decrease food intake,4 and reduce body weight in patients with type 2 diabetes. Tirzepatide can increase insulin sensitivity. | Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) are expressed throughout the body, including pancreatic beta-cells and the gastrointestinal tract. They have been implicated in the pathophysiology of type II diabetes mellitus as GLP-1R signalling is involved in glucose control by enhancing glucose-stimulated insulin secretion, delaying gastric transit, decreasing plasma glucagon levels, and reducing body weight by activating anorexigenic pathways in the brain. Both glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are peptide hormones involved in glucose homeostasis: they promote glucose-stimulated insulin secretion from the pancreatic beta-cells. However, GIP is the main incretin hormone that exerts insulinotropic effects in response to food intake. | There is limited information regarding the LD50 and overdose of tirzepatide. In case of an overdosage, appropriate supportive treatment should be initiated with a sufficient amount of time for observation and treatment, as tirzepatide has a long half-life. | Tirzepatide is metabolized by proteolytic cleavage of the peptide backbone, beta-oxidation of the C20 fatty diacid moiety, and amide hydrolysis. | Over the dose range of 1-5 mg, the Cmax of tirzepatide ranged from 108 to 397 ng/mL.The mean absolute bioavailability of tirzepatide following subcutaneous administration is 80%. Following subcutaneous administration, the Tmax ranged from eight to 72 hours. The steady-state plasma concentrations were achieved following four weeks of once-weekly subcutaneous administration. | Following subcutaneous administration, the mean steady-state volume of distribution was 9.5 L. The mean apparent steady-state volume of distribution of tirzepatide following subcutaneous administration in patients with type 2 diabetes mellitus was approximately 10.3 L. | The apparent population mean clearance of tirzepatide is 0.061 L/h.4 The mean steady-state apparent clearance of tirzepatide was 0.056 L/h. | Amino Acids, Peptides, and Proteins,Blood Glucose Lowering Agents,Gastrointestinal Hormones,GLP-1 Agonists,Hormones,Hormones, Hormone Substitutes, and Hormone Antagonists,Incretins,Nerve Tissue Proteins,Neuropeptides,Peptide Hormones,Peptides,Proteins | NA | NA | NA | NA | Glucagon-like peptide 1 receptor, Gastric inhibitory polypeptide | Mounjaro | Eli Lilly and Company | Eli Lilly and Company | Subcutaneous | 12.5 mg/0.5mL | MOUNJARO is contraindicated in patients with: A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, dizziness, fast heart rate, shaking, sweating, nervousness, anxiety, irritability, confusion, dizziness, hunger, pain in the upper right side of your abdomen, pain spreading to your back or below the shoulder blade, nausea, vomiting, fever, yellowing of the skin and eyes (jaundice), clay-colored stools, and bloating of the abdomen | MOUNJARO (tirzepatide) injection, for subcutaneous use, contains tirzepatide, a once weekly GIP receptor and GLP-1 receptor agonist. It is a 39-amino-acid modified peptide based on the GIP sequence. Tirzepatide contains 2 non-coded amino acids (aminoisobutyric acid, Aib) in positions 2 and 13, a C-terminal amide, and Lys residue at position 20 that is attached to 1,20-eicosanedioic acid via a linker. | Mounjaro (tirzepatide) Injection is a prescription medicine used to treat the symptoms of Type 2 Diabetes Mellitus. | NA | MOUNJARO is a clear, colorless to slightly yellow, sterile, preservative-free solution for subcutaneous use. Each singledose pen contains a 0.5 mL solution of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg of tirzepatide and the following excipients: sodium chloride (4.1 mg), sodium phosphate dibasic heptahydrate (0.7 mg), and water for injection. Hydrochloric acid solution and/or sodium hydroxide solution may have been added to adjust the pH. MOUNJARO has a pH of 6.5 – 7.5. | Link | Link | NA |