IMPORTANT PRODUCT INFORMATION

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

• Acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin.
• Nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended.

Selected Important Safety Information

EMEND is contraindicated in patients who are hypersensitive to any component of the product.

EMEND is a dose-dependent inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4). EMEND should not 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, including chemotherapy agents, 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. When EMEND is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced, and this may result in decreased efficacy of aprepitant.

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 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 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.

Coadministration of EMEND with warfarin (a CYP2C9 substrate) 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 EMEND with each chemotherapy cycle.

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

In clinical trials of EMEND in patients receiving highly emetogenic chemotherapy, the most common adverse events reported at a frequency greater than with standard therapy, and at an incidence of 1% or greater were hiccups (4.6% EMEND vs 2.9% standard therapy), asthenia/fatigue (2.9% vs 1.6%), increased ALT (2.8% vs 1.5%), increased AST (1.1% vs 0.9%), constipation (2.2% vs 2.0%), dyspepsia (1.5% vs 0.7%), diarrhea (1.1% vs 0.9%), headache (2.2% vs 1.8%), and anorexia (2.0% vs 0.5%).

In clinical trials of EMEND in patients receiving moderately emetogenic chemotherapy, the most common adverse events reported at a frequency greater than with standard therapy were eructation (1.0% EMEND vs 0.1% standard therapy) and fatigue (1.4% vs 0.9%).

Before prescribing EMEND, please read the Prescribing Information.