<p><strong>Pediatric Use</strong>: The safety and effectiveness in pediatric patients have not been established. In a dose-escalation, safety, and tolerability study, 21 patients ages 2 to 21 years (median age 12.9) with solid tumors received Aflibercept at doses ranging from 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, below the dose known to be safe and effective in adults with mCRC.<br />
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<strong>Geriatric Use</strong>: Of the 611 patients with mCRC, patients treated with Aflibercept/FOLFIRI, 205 (34%) were 65 years or older, and 33 (5%) were 75 years or older. Elderly patients (&ge;65 years of age) experienced higher incidences (&ge;5%) of diarrhea, dizziness, asthenia, weight decrease, and dehydration when compared to younger patients. Monitor elderly patients more closely for diarrhea and dehydration<br />
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The effect of Aflibercept on overall survival was similar in patients &lt;65 years old and &ge;65 years old who received Aflibercept/FOLFIRI. No dose adjustment of Aflibercept is recommended for patients greater than or equal to 65 years of age.<br />
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<strong>Hepatic Impairment:&nbsp;</strong>No dedicated clinical studies have been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of ziv-aflibercept. Based on a population PK analysis with data from 1507 patients, ziv-aflibercept exposure in patients with mild and moderate hepatic impairment were similar to those in patients with normal hepatic function. There are no data available for patients with severe hepatic impairment.<br />
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<strong>Renal Impairment</strong>: No dedicated clinical studies have been conducted to evaluate the effect of renal impairment on the pharmacokinetics of ziv-aflibercept. Based on a population PK analysis with data from 1507 patients, ziv-aflibercept exposure in patients with mild, moderate, and severe renal impairment were similar to those in patients with normal renal function [see&nbsp;Clinical Pharmacology.<br />
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<strong>Females and Males of Reproductive Potential</strong>: Male and female reproductive function and fertility may be compromised during treatment with Aflibercept, as suggested by findings in monkeys [see&nbsp;Nonclinical Toxicology. These animal findings were reversible within 18 weeks after cessation of treatment. Females and males of reproductive potential should use highly effective contraception during and up to a minimum of 3 months after the last dose of treatment.</p>