Zaltrap

Aflibercept is a recombinant fusion protein that works as a decoy receptor for two ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It stops these ligands from binding to the endothelial receptors VEGFR-1 and VEGFR-2, so neovascularization is suppressed and vascular permeability goes down. In the end, this slows vision loss or the progression of metastatic colorectal cancer.

Aflibercept is a pregnancy category C medicine. There are no adequate and well-controlled studies of Aflibercept in pregnant women. In rabbits, it was embryotoxic and teratogenic at exposure levels lower than human exposures at the recommended dose, and the fetuses showed more external, visceral and skeletal malformations. So Aflibercept should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It isn't known whether Aflibercept passes into human milk. Many drugs do pass into milk, and Aflibercept could cause serious adverse reactions in nursing infants. For this reason, a decision should be made either to stop nursing or to stop the drug, taking into account how important the drug is to the mother.

Pediatric use: The safety and effectiveness of Aflibercept in pediatric patients have not been established. In one dose-escalation study of safety and tolerability, 21 patients aged 2 to 21 years (median age 12.9) with solid tumors were given Aflibercept at doses of 2 to 3 mg/kg, IV, every two weeks. The pharmacokinetics of free ziv-Aflibercept were evaluated in 8 of these patients (ages 5 to 17 years). The maximum tolerated dose in the study was 2.5 mg/kg, which is below the dose known to be safe and effective in adults with mCRC.

Geriatric use: Of the 611 patients with mCRC who were treated with Aflibercept/FOLFIRI, 205 (34%) were 65 years or older and 33 (5%) were 75 years or older. Elderly patients (≥65 years of age) had higher incidences (≥5%) of diarrhea, dizziness, asthenia, weight decrease and dehydration than younger patients. Monitor elderly patients more closely for diarrhea and dehydration. The effect of Aflibercept on overall survival was similar in patients <65 years old and ≥65 years old who received Aflibercept/FOLFIRI. No dose adjustment of Aflibercept is recommended for patients 65 years of age or older.

Hepatic impairment: No dedicated clinical studies have looked at the effect of hepatic impairment on the pharmacokinetics of ziv-Aflibercept. A population PK analysis with data from 1507 patients showed that ziv-Aflibercept exposure in patients with mild and moderate hepatic impairment was similar to that in patients with normal hepatic function. There are no data for patients with severe hepatic impairment.

Renal impairment: No dedicated clinical studies have looked at the effect of renal impairment on the pharmacokinetics of ziv-Aflibercept. A population PK analysis with data from 1507 patients showed that ziv-Aflibercept exposure in patients with mild, moderate and severe renal impairment was similar to that in patients with normal renal function (see Clinical Pharmacology).

Females and males of reproductive potential: Findings in monkeys suggest that male and female reproductive function and fertility may be compromised during treatment with Aflibercept (see Nonclinical Toxicology). These animal findings were reversible within 18 weeks after treatment stopped. Females and males of reproductive potential should use highly effective contraception during treatment and for at least 3 months after the last dose.

No overdose has been reported with Aflibercept. Nothing is known about the safety of Aflibercept at doses above 7 mg per kg every 2 weeks or 9 mg per kg every 3 weeks.

Keep Aflibercept vials in a refrigerator at 2 to 8° C. Leave each vial in its original outer carton, because the carton protects it from light.