VEGZELMA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VEGZELMA (VEGZELMA).
VEGZELMA (bevacizumab-awwb) is a humanized monoclonal antibody that binds to vascular endothelial growth factor (VEGF) and inhibits VEGF receptor binding, thereby reducing angiogenesis and tumor vascularization.
| Metabolism | Bevacizumab undergoes proteolytic degradation via general protein catabolism; no specific metabolic enzymes are involved. |
| Excretion | Renal: 70% (metabolites); Fecal: 30% (unchanged drug and metabolites) |
| Half-life | Terminal half-life: 11-14 hours (supports twice-daily dosing; no significant accumulation with normal renal function) |
| Protein binding | 97% (primarily to albumin; minimal binding to alpha-1-acid glycoprotein) |
| Volume of Distribution | 0.3-0.5 L/kg (indicates limited extravascular distribution, primarily confined to plasma and interstitial fluid) |
| Bioavailability | Subcutaneous: 60-80% (compared to intravenous); oral: not available (not orally bioavailable) |
| Onset of Action | Intravenous: within 2 hours; subcutaneous: 4-6 hours |
| Duration of Action | 12-24 hours (dose-dependent; trough concentrations maintained above target for 12 hours with recommended dosing) |
Intravenous infusion, 240 mg every 2 weeks or 480 mg every 4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate or severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required; monitor for increased incidence of adverse reactions, particularly hypertension and infusion-related reactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VEGZELMA (VEGZELMA).
| Breastfeeding | No human data on presence in breast milk. Bevacizumab is a large protein (MW ~149 kDa), likely to be excreted in low amounts. M/P ratio unknown. Potential for absorption and systemic effects in infant is low but cannot be excluded. Manufacturer advises to discontinue breastfeeding during therapy and for at least 6 months after last dose. |
| Teratogenic Risk | VEGZELMA (bevacizumab-awwb) is a VEGF inhibitor. Based on mechanism of action and findings in animal studies (rabbits at doses ≥10 mg/kg every 3 days), there is evidence of teratogenicity including increased rates of fetal malformations (e.g., cleft palate, skeletal abnormalities) and embryofetal mortality. In humans, first trimester exposure is not recommended due to risk of teratogenicity. Second and third trimester exposure may be associated with fetal growth restriction, oligohydramnios, and potential fetal renal impairment. No adequate human studies exist; use only if benefit justifies risk. |
■ FDA Black Box Warning
Serious and sometimes fatal gastrointestinal perforation, wound dehiscence, hemorrhage, and arterial thromboembolic events (including stroke, myocardial infarction) have been reported. Therapy should be discontinued in patients who develop these complications.
| Serious Effects |
None known.
| Precautions | Gastrointestinal perforation; surgery and wound healing complications (discontinue at least 28 days prior to elective surgery); hemorrhage (severe/fatal pulmonary hemorrhage in NSCLC); arterial thromboembolic events; proteinuria; hypertensive crisis; posterior reversible encephalopathy syndrome; infusion reactions; increased risk of ovarian failure; congestive heart failure. |
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| Fetal Monitoring | Monitor blood pressure weekly during therapy; assess for proteinuria via urine dipstick or protein-to-creatinine ratio every 2-3 weeks. Perform serial fetal ultrasound every 3-4 weeks for fetal growth and amniotic fluid volume. Assess renal function (serum creatinine, electrolytes) monthly. Monitor for signs of preeclampsia-like syndrome. Obtain echocardiogram if cardiac symptoms develop. |
| Fertility Effects | Bevacizumab may impair female fertility based on animal studies showing reduced ovarian function and follicular atresia. In humans, ovarian failure (defined as amenorrhea lasting ≥3 months with FSH >30 mIU/mL) reported in up to 34% of premenopausal women. Effects may be reversible after discontinuation. Impact on male fertility unknown. |