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| Primary information |
|---|
| ID | 10385 |
| Therapeutic ID | Th1061 |
| Protein Name | Trastuzumab |
| Sequence | >Th1061_Trastuzumab
DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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| Molecular Weight | 145531.5 |
| Chemical Formula | C6470H10012N1726O2013S42 |
| Isoelectric Point | 8.45 |
| Hydrophobicity | -0.415 |
| Melting point | 71 |
| Half-life | average 28.5 days |
| Description | A recombinant IgG1 kappa, humanized monoclonal antibody that selectively binds with high affinity in a cell-based assay (Kd = 5 nM) to the extracellular domain of the human epidermal growth factor receptor protein. Produced in CHO cell culture. |
| Indication/Disease | For treatment of early stage HER2-positive breast cancer, or metastatic breast cancer that substantially overexpress HER2. |
| Pharmacodynamics | Used in the treatment of HER2-positive breast cancer. HER2 protein overexpression is observed in 25%-30% of primary breast cancers.Trastuzumab has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumorcells that overexpress HER2. It is a mediator of antibody dependent cellular cytotoxicity, in that the binding of the antibody to HER2 overexpressing cells leads to preferential cell death. |
| Mechanism of Action | Trastuzumab binds to the HER2 (or c-erbB2) proto-oncogene, an EGF receptor-like protein found on 20-30% of breast cancer cells. The binding leads to antibody mediated (complement mediated) killing of the HER2 positive cells. |
| Toxicity | Administration of trastuzumab can result in ventricular dysfunction and congestive heart failure. Risk of cardiotocity is especially elevated in patients recieving concurrent anthracycline or cyclophosphamide therapy. |
| Metabolism | Most likely removed by opsonization via the reticuloendothelial system. |
| Absorption | Peak and trough plasma concentrations at steady state (between weeks 16 and 32) were approximately 123 and 79 mcg/mL, respectively. At the highest weekly dose studied (500 mg), mean peak serum concentration was 377 mcg/mL |
| 44 mL/kg |
| Clearance | The predicted steady-state clearance of trastuzumab is 0.173 - 0.337 L/day, dependent primarily on the dosing regimen. The clearance rate for subcutaneously administered trastuzumab, formulated with hyaluronidase for improved subcutaneous absorption, is 0.11 L/day. |
| Categories | Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Antineoplastic Agents, Immunological, Antineoplastic and Immunomodulating Agents, Blood Proteins, Cancer immunotherapy, Cardiotoxic antineoplastic agents, Globulins, HER2 Receptor Antagonist, HER2/Neu/cerbB2 Antagonists, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Immunotherapy, Narrow Therapeutic Index Drugs, Proteins, Serum Globulins |
| Patents Number | CA2103059 |
| Date of Issue | 22-Mar-2005 |
| Date of Expiry | 15-Jun-2012 |
| Drug Interaction | Abciximab may increase the risk of a hypersensitivy reaction to Trastuzumab |
| Target | Receptor tyrosine-protein kinase erbB-2 |
| Brand Name | Truxima |
| Company | Celltrion, Cephalon, Inc. |
| Brand Description | Celltrion, Cephalon, Inc. |
| Prescribed For | Adjuvant Breast Cancer, Metastatic Breast Cancer, Metastatic Gastric Cancer |
| Chemical Name | NA |
| Formulation | Each multi-use vial of Herceptin contains 440 mg trastuzumab, 400 mg a,a-trehalose dihydrate, 9.9 mg L-histidine HCl, 6.4 mg L-histidine, and 1.8 mg polysorbate 20, USP. Reconstitution with 20 mL of the appropriate diluent (BWFI or SWFI) yields a solution containing 21 mg/mL trastuzumab, at a pH of approximately 6 |
| Physical Appearance | Herceptin is a sterile, white to pale yellow, preservative-free lyophilized powder |
| Route of Administration |  Intravenous administration |
| Recommended Dosage | Initial dose of 4mg/kg for 90 minutes and after that 2mg/kg weekly for 30 minutes during chemotherapy for the first 12 weeks incase of breast cancer. Last Dose 6mg/kg for 3 weeks. |
| Contraindication | None |
| Side Effects | Cardiomyopathy, Infusion reactions, Embryo-fetal Toxicity, Pulmonary toxicity,Exacerbation of chemotherapy-induced neutropenia, ever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |