Overview
11 DESCRIPTION Bevacizumab-adcd is a vascular endothelial growth factor inhibitor. Bevacizumab-adcd is a recombinant humanized monoclonal IgG1 antibody that contains human framework regions and murine complementarity-determining regions. Bevacizumab-adcd has an approximate molecular weight of 149 kDa. Bevacizumab-adcd is produced in a mammalian cell (Chinese Hamster Ovary) expression system.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Bevacizumab products bind VEGF and prevent the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Administration of bevacizumab to xenotransplant models of colon cancer in nude (athymic) mice caused reduction of microvascular growth and inhibition of metastatic disease progression. 12.2 Pharmacokinetics The pharmacokinetic profile of bevacizumab was assessed using an assay that measures total serum bevacizumab concentrations (i.e., the assay did not distinguish between free bevacizumab and bevacizumab bound to VEGF ligand).
Indications
- 1 INDICATIONS AND USAGE VEGZELMA is a vascular endothelial growth factor inhibitor indicated for the treatment of: Metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment. ( 1.1 ) Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen. ( 1.1 ) Limitations of Use : VEGZELMA is not indicated for adjuvant treatment of colon cancer. ( 1.
Common Doses
- 5 mg
- 10 mg
- 7.5 mg
- 15 mg
Dosage
2 DOSAGE AND ADMINISTRATION Withhold for at least 28 days prior to elective surgery. Do not administer VEGZELMA for 28 days following major surgery and until adequate wound healing. ( 2.1 ) Metastatic colorectal cancer ( 2.2 ) 5 mg/kg every 2 weeks with bolus-IFL 10 mg/kg every 2 weeks with FOLFOX4 5 mg/ kg every 2 weeks or 7.5 mg/kg every 3 weeks with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin based chemotherapy after progression on a first-line bevacizumab product containing regimen First-line non−squamous non−small cell lung cancer ( 2.
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Gastrointestinal Perforations and Fistulae [see Warnings and Precautions (5.1) ] . Surgery and Wound Healing Complications [see Warnings and Precautions (5.2) ]. Hemorrhage [see Warnings and Precautions (5.3) ]. Arterial Thromboembolic Events [see Warnings and Precautions (5.4) ]. Venous Thromboembolic Events [see Warnings and Precautions (5.5) ]. Hypertension [see Warnings and Precautions (5.6) ]. Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Effects of VEGZELMA on Other Drugs No clinically meaningful effect on the pharmacokinetics of irinotecan or its active metabolite SN38, interferon alfa, carboplatin or paclitaxel was observed when bevacizumab was administered in combination with these drugs; however, 3 of the 8 patients receiving bevacizumab with paclitaxel and carboplatin had lower paclitaxel exposure after four cycles of treatment (at Day 63) than those at Day 0, while patients receiving paclitaxel and carboplatin alone had a greater paclitaxel exposure at Day 63 than at Day 0.