EMEND, in combination with other antiemetic agents, is indicated 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.
•   Postoperative nausea and vomiting.

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.

EMEND is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3
receptor antagonist. The recommended dosage includes EMEND (125 mg) on Day 1 followed
by EMEND (80 mg) once daily on Days 2 and 3. EMEND for Injection (115 mg) may be
substituted for EMEND 30 minutes before chemotherapy, on Day 1 only, as an infusion
administered over 15 minutes.

Caution: EMEND for Injection should not be mixed or reconstituted with solutions for which
physical and chemical compatibility have not been established. EMEND for Injection is
incompatible with any solutions containing divalent cations (eg, Ca2+, Mg2+), including Lactated
Ringer's Solution and Hartmann's Solution.

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 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.

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.

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