Important Safety Information
EMEND and EMEND for Injection, in combination with other antiemetic agents, are 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.
EMEND and EMEND for Injection have not been studied for treatment of established nausea and
vomiting. Chronic continuous administration of EMEND or EMEND for Injection is not recommended.
Selected Important Safety Information
- EMEND for Injection is contraindicated in patients who are hypersensitive to EMEND for
Injection, aprepitant, polysorbate 80, or any other components of the product. Known
hypersensitivity reactions include flushing, erythema, dyspnea, and anaphylactic reactions.
- Aprepitant, 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 or cisapride. Inhibition of CYP3A4 by aprepitant could result in
elevated plasma concentrations of these drugs, potentially causing serious or life-threatening
reactions.
- 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 and EMEND for Injection 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 or EMEND for Injection is used concomitantly with another
CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When EMEND or EMEND for
Injection 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.
- There have been isolated reports of immediate hypersensitivity reactions including flushing,
erythema, dyspnea, and anaphylaxis during infusion of fosaprepitant. These hypersensitivity
reactions have generally responded to discontinuation of the infusion and administration of
appropriate therapy. It is not recommended to reinitiate the infusion in patients who have
experienced these symptoms during first-time use.
- Coadministration of EMEND and EMEND for Injection 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 or EMEND for Injection 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 or EMEND for Injection. Alternative or backup methods of
contraception should be used during treatment with and for 1 month after the last dose of EMEND or
EMEND for Injection.
- Chronic continuous use of EMEND or EMEND for Injection 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%).
- In a clinical trial evaluating safety of the 1-day regimen of EMEND for Injection 150 mg
compared with the 3-day regimen of EMEND, the safety profile was generally similar to that seen in
prior highly emetogenic chemotherapy studies with aprepitant. However, infusion-site reactions
occurred at a higher incidence in patients who received fosaprepitant (3.0%) than in those who
received aprepitant (0.5%). Those infusion-site reactions included infusion-site erythema,
infusion-site pruritus, infusion-site pain, infusion-site induration, and infusion-site
thrombophlebitis.
Before prescribing EMEND or EMEND for Injection, please read the Prescribing
Information. The Patient
Information also is available.