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| Primary information |
|---|
| ID | 10484 |
| Therapeutic ID | Th1091 |
| Protein Name | Bevacizumab |
| Sequence | >Th1091_Bevacizumab
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVGWINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| Molecular Weight | 149000 |
| Chemical Formula | C6538H10034N1716O2033S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | 61 (FAB fr |
| Half-life | 20 days (range of 11-50 days) |
| 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 | Bevacizumab toxicities are distinct from the effects of cytotoxic agents used in chemotherapy, and are normally linked to impaired VEGF function.18,19 Common toxicities associated with bevacizumab include hypertension, gastrointestinal perforation, arterial thromboembolism, reversible posterior leukoencephalopathy syndrome (RPLS), venous thromboembolism, proteinuria, bleeding/hemorrhage, and wound-healing complications |
| Metabolism | There are several pathways through which monoclonal antibodies (mAbs) may be cleared. Non-specific clearance of mAbs refers to target independent pinocytosis, and proteolysis of the protein into small amino acids and peptides in the reticuloendothelial system (RES) and the liver. Target-mediated clearance is a result of specific interactions between the mAb and its target antigen. Once bound, the antibody-antigen complex may be cleared via lysosomal degradation. Additionally, the production of anti-drug antibodies (ADA), which are a result of an immunogenic response to mAb-based treatment, can form complexes with mAb’s and may impact the rate of mAb clearance |
| Absorption | Monoclonal antibodies (mAbs) are large in size, do not readily cross cell membranes, and are unable to withstand proteolysis in the gastrointestinal tract.Given these characteristics, mAbs are poorly absorbed via the oral route and are instead administered intravenously, intramuscularly or subcutaneously.In a single dose (1mg/kg) pharmacokinetic study assessing the bioequivalence of bevacizumab and TAB008 (a biosimilar product), the pharmacokinetic parameters of Avastin (bevacizumab) were as follows: Geometric mean Cmax = 17.38 ug/mL Geometric mean AUCinf = 5,358 ugxh/mL Geometric mean Tmax = 2.50 hrs |
| The volume of distribution of bevacizumab is approximately 3.29 L and 2.39 L for the average male and female, respectively. |
| Clearance | The clearance (CL) of bevacizumab is approximately 0.207 L/day. The CL of bevacizumab can increase or decrease by 30% in patients who weigh >114 kg or <49 kg respectively. Males tend to clear bevacizumab at a faster rate than females (26% faster on average). Other factors including alkaline phosphatase (ALP), serum aspartate aminotransferase (AST), serum albumin, and tumor burden may cause the CL to fluctuate |
| Categories | Amino Acids, Peptides, and Proteins,Angiogenesis Inhibitors,Angiogenesis Modulating Agents,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Antineoplastic Agents,Antineoplastic Agents, Immunological,Antineoplastic and Immunomodulating Agents,Blood Proteins,Cancer immunotherapy,Cardiotoxic antineoplastic agents,Experimental Unapproved Treatments for COVID-19,Globulins,Growth Inhibitors,Immunoglobulins,Immunoproteins,Immunotherapy,Narrow Therapeutic Index Drugs,Proteins,Serum Globulins,Vascular Endothelial Growth Factor Inhibitor,Vascular Endothelial Growth Factor Inhibitors,Vascular Endothelial Growth Factor-directed Antibody Interactions |
| Patents Number | CA2286330 |
| Date of Issue | 10-Jun-2008 |
| Date of Expiry | 3-Apr-2018 |
| Drug Interaction | NA |
| Target | Vascular endothelial growth factor A,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 |
| Brand Name | Avastin |
| Company | Genentech |
| Brand Description | Genentech |
| 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 | NA |
| 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. |
| Physical Appearance | 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 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |