ZIRABEV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZIRABEV (ZIRABEV).
ZIRABEV (bevacizumab-awwb) is a vascular endothelial growth factor (VEGF) inhibitor. It binds to VEGF-A and prevents its interaction with VEGFR-1 and VEGFR-2 receptors on endothelial cells, thereby inhibiting angiogenesis.
| Metabolism | Not extensively metabolized; primarily eliminated via proteolytic catabolism. |
| Excretion | ZIRABEV (bevacizumab) is eliminated primarily via metabolic degradation in the reticuloendothelial system. Renal excretion is minimal (<1% as unchanged drug in urine). Biliary/fecal excretion accounts for the remainder of metabolites. |
| Half-life | Terminal elimination half-life is approximately 20 days (range 11-50 days). This long half-life supports extended dosing intervals (e.g., every 2-3 weeks). |
| Protein binding | Bevacizumab is approximately 95% bound to plasma proteins (likely albumin). |
| Volume of Distribution | Volume of distribution (Vd) at steady state is about 2.9-3.1 L/kg, indicating distribution primarily within the vascular and interstitial spaces, consistent with a large monoclonal antibody. |
| Bioavailability | Intravenous: 100% (not administered via other routes). Subcutaneous absorption is minimal and not clinically used; subcutaneous bioavailability has not been characterized. |
| Onset of Action | Intravenous: Clinical antiangiogenic effects (e.g., reduction in vascular permeability) may be observed within 1-2 weeks after first dose, though maximal response may require multiple doses. |
| Duration of Action | Pharmacodynamic effects (e.g., suppression of tumor angiogenesis) persist for several weeks after drug clearance due to sustained VEGF inhibition. Dosing interval is typically 2-3 weeks. |
15 mg/kg intravenously over 60 minutes on Day 1 of each 3-week cycle
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >= 30 mL/min). Insufficient data for severe renal impairment (CrCl < 30 mL/min) or dialysis. |
| Liver impairment | No dose adjustment recommended for Child-Pugh A or B. Not studied in Child-Pugh C; use with caution. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required based on age alone; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZIRABEV (ZIRABEV).
| Breastfeeding | Human data are lacking. Bevacizumab is a large monoclonal antibody likely excreted into breast milk in low amounts but may be orally degraded. M/P ratio is unknown. Risk of neonatal systemic absorption and immunosuppression is theoretical. Breastfeeding is not recommended during therapy and for at least 6 months after last dose. |
| Teratogenic Risk | ZIRABEV (bevacizumab) is contraindicated in pregnancy due to its anti-angiogenic mechanism. First trimester exposure is associated with increased risk of fetal malformations (e.g., skeletal anomalies, omphalocele) and spontaneous abortion. Second and third trimester exposure can cause fetal renal impairment, oligohydramnios, and fetal growth restriction due to inhibition of placental vascular development. |
■ FDA Black Box Warning
Gastrointestinal perforations, wound dehiscence, and hemorrhage (including fatal hemoptysis) have been reported. Discontinue ZIRABEV in patients with these events.
| Serious Effects |
["Known hypersensitivity to bevacizumab or any excipient","Surgery within 28 days of planned treatment or unhealed surgical incision"]
| Precautions | ["Gastrointestinal perforations","Wound dehiscence","Hemorrhage (including severe or fatal hemoptysis)","Arterial thromboembolic events (e.g., stroke, myocardial infarction)","Venous thromboembolic events (e.g., pulmonary embolism)","Hypertension (including hypertensive crisis)","Posterior reversible encephalopathy syndrome (PRES)","Renal injury and proteinuria","Congestive heart failure","Ovarian failure","Fetal harm (use effective contraception during and for 6 months after treatment)"] |
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| Fetal Monitoring | Baseline and serial blood pressure monitoring, urinalysis for proteinuria, and renal function tests (serum creatinine, BUN) every 2-3 weeks. Pregnant patients require close fetal surveillance with ultrasound for fetal growth, amniotic fluid volume, and Doppler velocimetry; monitor for hypertension and proteinuria (pre-eclampsia-like syndrome). |
| Fertility Effects | Bevacizumab may impair ovarian function and fertility in females due to anti-angiogenic effects on ovarian vasculature. Reversibility is uncertain. Advise fertility preservation counseling. Effects on male fertility are unknown. |