Primary information |
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ThPP ID | Th1061 |
Therapeutic Peptide/Protein Name | Trastuzumab |
Sequence | Light chain 1: DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAW view full sequnce in fasta |
Functional Classification | IIa |
Molecular Weight | 145531.5 |
Chemical Formula | C6470H10012N1726O2013S42 |
Isoelectric Point | 8.45 |
Hydrophobicity | -0.415 |
Melting Point (℃) | 61 (FAB f |
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 | N.A. |
Volume of Distribution | 44 mL/kg |
Clearance | N.A. |
Categories | Antineoplastic Agents |
Patents Number | CA2103059 |
Date of Issue | 23/03/09 |
Date of Expiry | 16/06/16 |
Drug Interaction | Abciximab may increase the risk of a hypersensitivy reaction to Trastuzumab |
Target | N.A. |
Information of corresponding available drug in the market |
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Brand Name | Herceptin |
Company | Genentech |
Brand Discription | Herceptin (trastuzumab) 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 is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture containing the antibiotic gentamicin |
Prescribed for | Adjuvant Breast Cancer, Metastatic Breast Cancer, Metastatic Gastric Cancer |
Chemical Name | N.A. |
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 |
Physcial Appearnce | Herceptin is a sterile, white to pale yellow, preservative-free lyophilized powder |
Route of Administration | Â 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 | http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=492dbdb2-077e-4064-bff3-372d6af0a7a2 http://www.rxlist.com/herceptin-drug.htm |
PubMed ID | 21813259, 14613027, 14528282, 12908564, 25572781, 25547504, 25532690, 25494663 |
3-D Structure | Th1061 (View) or (Download) |