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| Primary information |
|---|
| ID | 10388 |
| Therapeutic ID | Th1061 |
| Protein Name | Trastuzumab |
| Sequence | >Th1061_Trastuzumab
DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
|
| 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 |
| 47 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 | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | Abatacept, Adalimumab, Alemtuzumab, Altretamine, Amsacrine, Anakinra, Asparaginase, Azacitidine, Azathioprine, Basiliximab, Betamethasone, Bleomycin, Busulfan, Capecitabine, Carboplatin, Carmustine, Chlorambucil, Cisplatin, Cladribine, Clofarabine, Corticotropin, Cortisone acetate, Cyclophosphamide, Cyclosporine, Cytarabine, Dacarbazine, Daclizumab, Dactinomycin, Denileukin diftitox, Dexamethasone, Docetaxel, Efalizumab, Erlotinib, Estramustine, Etanercept, Etoposide, Floxuridine, Fludarabine, Fludrocortisone, Fluorouracil, Gefitinib, Gemcitabine, Hydrocortisone, Hydroxyurea, Ibritumomab, Ifosfamide, Imatinib, Infliximab, Irinotecan, Lenalidomide, Lomustine, Mechlorethamine, Melphalan, Mercaptopurine, Methotrexate, Methylprednisolone, Mitomycin, Mitoxantrone, Muromonab, Mycophenolate mofetil, Mycophenolic acid, Natalizumab, Nelarabine, Nilotinib, Oxaliplatin, Pegaspargase, Pentostatin, Prednisolone, Prednisone, Procarbazine, Rilonacept, Rituximab, Sirolimus, Sorafenib, Streptozocin, Sunitinib, Tacrolimus, Temozolomide, Temsirolimus, Teniposide, Thalidomide, Thiotepa, Tioguanine, Tofacitinib, Topotecan, Tositumomab, Tretinoin, Triamcinolone, Vinblastine, Vincristine, Vinorelbine may increase the risk of neutropenia and anemia with trastuzumab. Monitor closely for signs and symptoms of adverse events. |
| Target | NA |
| Brand Name | Ogivri |
| Company | Mylan Institutional LLC, Viatris Limited, Bgp Pharma Ulc |
| Brand Description | Mylan Institutional LLC, Viatris Limited, Bgp Pharma Ulc |
| Prescribed For | treatment of HER2-overexpressing breast cancer, and the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. |
| Chemical Name | NA |
| Formulation | Ogivri (trastuzumab-dkst) is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2. Trastuzumab-dkst is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture. |
| Physical Appearance | sterile, off-white to pale yellow, preservative-free lyophilized powder |
| Route of Administration | intravenous administration. |
| Recommended Dosage | Initial dose of 4 mg/kg as an intravenous infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly during chemotherapy for the first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel/carboplatin). One week following the last weekly dose of Ogivri, administer Ogivri at 6 mg/kg as an intravenous infusion over 30 to 90 minutes every three weeks. |
| Contraindication | NA |
| Side Effects | headache, diarrhea, nausea, chills, fever, infection, congestive heart failure, insomnia, cough, rash, low white blood cell count (neutropenia), fatigue, anemia, swelling and sores inside the mouth, weight loss, upper respiratory tract infections, low platelet count (thrombocytopenia), mucosal inflammation, runny or stuffy nose, and changes in taste. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |