ZALTRAP
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZALTRAP (ZALTRAP).
Vascular endothelial growth factor (VEGF) trap; binds to VEGF-A, VEGF-B, and PlGF, inhibiting angiogenesis.
| Metabolism | Minimally metabolized; primarily via proteolysis into small peptides and amino acids. |
| Excretion | Primarily via the reticuloendothelial system and proteolytic catabolism; no significant renal or biliary excretion. Renal elimination accounts for <5% as intact drug. |
| Half-life | 17-18 days (terminal half-life) with clinical context supporting a dosing interval of every 2 weeks; steady-state achieved by approximately 16 weeks. |
| Protein binding | ~100% (primarily binds to soluble VEGF-A as a receptor decoy; also binds to FcRn recycling receptor). |
| Volume of Distribution | 3.0 L (central volume); apparent Vd ~5.6 L (total). Not assessed per kg; monoclonal antibodies typically distribute in plasma and interstitial space (approximately 0.04-0.09 L/kg). |
| Bioavailability | 100% (intravenous administration only; no data for other routes) |
| Onset of Action | Clinically observable reduction in tumor growth within weeks; exact onset difficult to define due to indirect mechanism. |
| Duration of Action | Sustained antiangiogenic effect; duration correlates with drug exposure and extends beyond elimination half-life due to VEGF inhibition; clinical effect persists for several weeks after last dose. |
| Molecular Weight | 115000 |
4 mg/kg intravenously over 1 hour every 2 weeks
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for mild (CrCl ≥60 mL/min) or moderate (CrCl 30-59 mL/min) renal impairment. Insufficient data for severe renal impairment or dialysis, use with caution. |
| Liver impairment | No adjustment for mild hepatic impairment (Child-Pugh A). Not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) due to potential toxicity. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment recommended. Monitor for adverse events such as hypertension, bleeding, and fatigue, which may be more frequent in elderly patients. |
| 1st trimester | Zaltrap (aflibercept) is an anti-VEGF agent. Animal studies have shown teratogenicity and embryotoxicity. Avoid use during first trimester. If exposure occurs, consider fetal monitoring. |
| 2nd trimester | Potential risk of fetal harm due to anti-VEGF effects. Use only if benefit outweighs risk. May cause oligohydramnios if used in second trimester. |
| 3rd trimester | Use in third trimester may cause oligohydramnios and fetal renal impairment. Avoid use near term due to risk of bleeding and poor wound healing. |
Clinical note
Comprehensive clinical and safety monograph for ZALTRAP (ZALTRAP).
| Placental transfer | Aflibercept is a large protein (fusion protein) and is expected to cross the placenta in minimal amounts due to its size. However, animal studies show fetal exposure and toxicities. The degree of placental transfer in humans is not well characterized. |
| Breastfeeding | It is not known whether aflibercept is excreted in human milk. Given the potential for adverse effects in the breastfed infant, breastfeeding is not recommended during therapy and for at least 3 months after the last dose. |
■ FDA Black Box Warning
Hemorrhage: Severe, sometimes fatal hemorrhage has occurred, including gastrointestinal hemorrhage. Monitor for signs and symptoms. Do not administer if recent hemorrhage.
| Serious Effects |
Hypersensitivity to aflibercept or any excipients
| Precautions | Hemorrhage: Increased risk of severe bleeding including gastrointestinal hemorrhage, Gastrointestinal perforation: Discontinue if occurs, Impaired wound healing: Withhold prior to surgery, Fistula formation: Increased risk, Hypertension: Monitor blood pressure, Arterial thromboembolic events: Increased risk in elderly, Neutropenia and infection: Monitor neutrophil counts, Reversible posterior leukoencephalopathy syndrome (RPLS): Discontinue if diagnosed, Proteinuria: Monitor urine protein, Ovarian failure and fertility impairment: May occur |
| Food/Dietary | No specific food interactions. Maintain adequate hydration to prevent chemotherapy-related side effects. Avoid grapefruit and grapefruit juice if taking concurrent medications that interact. |
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| Lactation Rating | L5 |
| Teratogenic Risk | ZALTRAP (aflibercept) is an anti-VEGF agent. Based on its mechanism of action and animal studies, it has potential teratogenic effects. In pregnant women, VEGF inhibition can cause fetal harm including impaired organogenesis, growth restriction, and increased fetal loss. Use is contraindicated in pregnancy. First trimester exposure may increase risk of malformations; second and third trimester exposure may cause oligohydramnios and fetal renal dysfunction. |
| Fetal Monitoring | If used during pregnancy, monitor fetal growth and amniotic fluid volume via ultrasound. Assess renal function and blood pressure. Consider serial fetal echocardiography due to potential cardiovascular effects. |
| Fertility Effects | Aflibercept may impair fertility in females. In animal studies, ovarian dysfunction and reduced fertility were observed. Reversal upon discontinuation is unknown. Men and women of childbearing potential should use effective contraception during and for at least 3 months after treatment. |
| Clinical Pearls | Zaltrap (ziv-aflibercept) is a VEGF inhibitor used with FOLFIRI for metastatic colorectal cancer. Monitor blood pressure closely as hypertension is common; premedicate with antiemetics for chemotherapy. Contraindicated with severe hemorrhage or recent surgery. Assess for proteinuria and thromboembolic events. Do not administer with live vaccines. |
| Patient Advice | Report any signs of bleeding, unusual bruising, or black stools immediately. · Regular blood pressure monitoring is required; you may need antihypertensive medication. · Avoid pregnancy; use effective contraception during and for 2 months after treatment. · Do not receive live vaccines while on Zaltrap. · Inform your doctor if you have severe diarrhea, mouth sores, or skin reactions. |