EMEND, in combination with other antiemetic agents, is indicated for prevention of:

SELECTED IMPORTANT RISK INFORMATION

EMEND is a 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; however, weak inhibition of CYP3A4 by a single 40-mg dose of EMEND is not expected to alter the plasma concentrations to a clinically significant degree. 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.

Although studies have not been done with the 40-mg single dose, the timing of administration of EMEND relative to ovulation could cause contraceptive failure.

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 or after administration of a single 40-mg dose of EMEND for prevention of postoperative nausea and vomiting.

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%).

The most frequent adverse events reported in clinical trials of EMEND for postoperative nausea and vomiting were constipation (8.5%), nausea (8.5%), pruritus (7.6%), pyrexia (5.9%), hypotension (5.7%), headache (5.0%), and bradycardia (4.4%).

Before prescribing EMEND, please read the Prescribing Information and Patient Product Information.