| Primary information |
|---|
| ThPP ID | Th1091 |
| Therapeutic Peptide/Protein Name | Bevacizumab |
| Sequence | DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYF view full sequnce in fasta |
| Functional Classification | IIa |
| Molecular Weight | 149000 |
| Chemical Formula | C6538H10034N1716O2033S44 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | 61 (FAB fr |
| Half Life | N.A. |
| Description | Recombinant (derived from CHO-gentamycin), humanized, monoclonal IgG1 antibody. It Inhibits the biologic activity of human vascular endothelial growth factor (VEGF) by binding to it. Comprises human framework regions and murine complementarity-determining regions. |
| Indication/Disease | As part of combination therapy for metastatic colorectal cancer and HER2-negative metastatic breast cancer. |
| Pharmacodynamics | Bevacizumab prevents or reduces the formation of blood vessels (angiogenesis) thereby preventing or reducing metatstatic disease progressing. Bevacizumab binds VEGF and prevents vascular endothelial growth and endothelial cell proliferation. |
| Mechanism of Action | Bevacizumab binds VEGF and prevents the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. This prevents blood vessel proliferation and tumour metastasis. |
| Toxicity | N.A. |
| Metabolism | Most likely removed by opsonization via the reticuloendothelial system when bound to endothelial cells, or by human antimurine antibody production |
| Absorption | N.A. |
| Volume of Distribution | N.A. |
| Clearance | 0.26 L/day [Male patients who received 1 to 20 mg/kg of Avastin weekly, every 2 weeks, or every 3 weeks] 0.21 L/day [Female patients who received 1 to 20 mg/kg of Avastin weekly, every 2 weeks, or every 3 weeks] 0.25 L/day [Patients with higher tumor burden who received 1 to 20 mg/kg of Avastin weekly, every 2 weeks, or every 3 weeks]* 0.2 L/day [patients with tumor burdens below the median who received 1 to 20 mg/kg of Avastin weekly, every 2 weeks, or every 3 weeks] |
| Categories | Angiogenesis Inhibitors |
| Patents Number | CA2286330 |
| Date of Issue | 11/06/12 |
| Date of Expiry | 04/04/22 |
| Drug Interaction | N.A. |
| Target | Interleukin-2 receptor subunit alpha,Interleukin-2 receptor subunit beta,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 immunoglobulin gamma Fc region receptor III-A,High affinity immunoglobulin gamma Fc receptor I,Low affinity immunoglobulin gamma Fc region receptor II-a,Low affinity immunoglobulin gamma Fc region receptor II-b,Low affinity immunoglobulin gamma Fc region receptor II-c |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Avastin |
| Company | Genentech |
| Brand Discription | Avastin (bevacizumab) is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF) in in vitro and in vivo assay systems. Bevacizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to VEGF. Avastin has an approximate molecular weight of 149 kD. Bevacizumab is produced in a mammalian cell (Chinese Hamster Ovary) expression system in a nutrient medium containing the antibiotic gentamicin. Gentamicin is not detectable in the final product. |
| Prescribed for | Metastatic Colorectal Cancer (mCRC): Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum. Non-Squamous Non-Small Cell Lung Cancer (NSCLC), glioblastoma with progressive disease in adult patients. Metastatic Renal Cell Carcinoma (mRCC): Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa. Persistent, Recurrent, Or Metastatic Carcinoma Of The Cervix: Avastin in combination with paclitaxel and cisplatin or paclitaxel and topotecan is indicated for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix. |
| Chemical Name | N.A. |
| Formulation | 100 mg product is formulated in 240 mg a,a-trehalose dihydrate, 23.2 mg sodium phosphate (monobasic, monohydrate), 4.8 mg sodium phosphate (dibasic, anhydrous), 1.6 mg polysorbate 20, and Water for Injection, USP. The 400 mg product is formulated in 960 mg a,a-trehalose dihydrate, 92.8 mg sodium phosphate (monobasic, monohydrate), 19.2 mg sodium phosphate (dibasic, anhydrous), 6.4 mg polysorbate 20, and Water for Injection, USP. |
| Physcial Appearnce | Slightly opalescent, colorless to pale brown, sterile, pH 6.2 solution |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | First infusion: Administer infusion over 90 minutes. Subsequent infusions: Administer second infusion over 60 minutes if first infusion is tolerated; Recommended Doses And Schedules: Metastatic Colorectal Cancer (mCRC).The recommended doses are 5 mg/kg or 10 mg/kg every 2 weeks when used in combination with intravenous 5-FU-based chemotherapy. Administer 5 mg/kg when used in combination with bolus-IFL. Administer 10 mg/kg when used in combination with FOLFOX4. Administer 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks when used in combination with a fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy regimen in patients who have progressed on a first-line Avastin-containing regimen. Non-Squamous Non-Small Cell Lung Cancer (NSCLC): The recommended dose is 15 mg/kg every 3 weeks in combination with carboplatin and paclitaxel. Glioblastoma: The recommended dose is 10 mg/kg every 2 weeks. Metastatic Renal Cell Carcinoma (mRCC): The recommended dose is 10 mg/kg every 2 weeks in combination with interferon alfa. Cervical Cancer: The recommended dose of Avastin is 15 mg/kg every 3 weeks as an Intravenous infusion administered in combination with one of the following chemotherapy regimens: paclitaxel and cisplatin, or paclitaxel and topotecan. |
| Contraindication | Do not administer as an intravenous push or bolus. Administer only as an intravenous (IV) infusion.. Do not initiate Avastin until at least 28 days following major surgery. Administer Avastin after the surgical incision has fully healed. |
| Side Effects | headache, confusion, vision problems, feeling very weak or tired, fainting, and seizure (blackout or convulsions) |
| Useful Link | http://www.rxlist.com/avastin-drug.htm http://www.avastin.com/patient/ http://maculacenter.com/eye-procedures/avastin/ |
| PubMed ID | 25638326, 25637137, 25631483, 25628268, 25627091, 25624888, 18343240, 18054637, 17409907 |
| 3-D Structure | Th1091 (View) or (Download) |