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IMPORTANT PRODUCT INFORMATION
EMEND for Injection, 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.
EMEND for
Injection has not been studied for treatment of established nausea and
vomiting. Chronic continuous administration of 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 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 for
Injection could result in elevated plasma concentrations of these concomitant
medications. Conversely, when EMEND for Injection is used concomitantly with
another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated.
When 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 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 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
for Injection. Alternative or backup methods of contraception should be used
during treatment with and for 1 month after the last dose of EMEND for
Injection.
Chronic continuous use of 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 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 for Injection, please read the Prescribing Information.
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