Selected Important Risk Information

EMEND is a weak to moderate (dose-dependent) CYP3A4 inhibitor. EMEND should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Inhibition of cytochrome P450 isoenzyme 3A4 (CYP3A4) by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

EMEND should be used with caution in patients receiving concomitant orally administered medicinal products, including chemotherapy agents, that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND 125 mg/80 mg could result in elevated plasma concentrations of these concomitant medicinal products. The effect of EMEND on the pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of EMEND on the pharmacokinetics of intravenously administered CYP3A4 substrates.

Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine. In clinical studies, EMEND 125 mg/80 mg was administered commonly with etoposide, vinorelbine, or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions. In a separate pharmacokinetic study, EMEND did not influence the pharmacokinetics of docetaxel.

Because a small number of patients in clinical studies received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied.

The efficacy of hormonal contraceptives may be reduced during coadministration with EMEND and for 28 days after the last dose of EMEND. Alternative or backup methods of contraception should be used during treatment with EMEND and for 1 month after the last dose of EMEND.

Chronic continuous use of EMEND for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during chronic continuous use.

Coadministration of EMEND with warfarin may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of EMEND with each chemotherapy cycle.

The most frequent adverse events reported in clinical trials of EMEND for highly emetogenic chemotherapy were asthenia/fatigue (17.8%), nausea (12.7%), hiccups (10.8%), constipation (10.3%), diarrhea (10.3%), and anorexia (10.1%).

The most frequent adverse events reported in clinical trials of EMEND for moderately emetogenic chemotherapy were alopecia (24.0%), fatigue (21.9%), headache (16.4%), constipation (12.3%), neutropenia (8.9%), dyspepsia (8.4%), stomatitis (5.3%), hot flush (3.0%), and pharyngolaryngeal pain (3.0%).

Before prescribing EMEND, please read the Prescribing Information. The Patient Information also is available.

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