Selected Important Risk Information

EMEND, when administered orally, is a moderate cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor. Because fosaprepitant is rapidly converted to aprepitant, neither drug should be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Inhibition of 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 medications that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND could result in elevated plasma concentrations of these concomitant medications. Conversely, when EMEND is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated.

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 separate pharmacokinetic studies, EMEND 125 mg/80 mg did not influence the pharmacokinetics of docetaxel or vinorelbine.

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.

There have been isolated reports of immediate hypersensitivity reactions including flushing, erythema, and dyspnea during infusion of fosaprepitant. These reactions have generally receded when the infusion was stopped and appropriate therapy was provided. It is not recommended to reinitiate the infusion in patients who have these reactions.

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%).

The most frequent clinical adverse events reported in patients receiving EMEND for Injection were infusion site pain (7.6%), headache (3.0%), and infusion site induration (1.5%).

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