s should be given their dose of EMEND for Injection as an infusion over 15 minutes, 30 minutes prior to chemotherapy on Day 1.
Allergic reactions, which may be serious, and may include hives, rash and itching and cause difficulty in breathing or swallowing, have been reported in general use with EMEND. Patients should be instructed to stop using EMEND and report to their doctor right away if they experience an allergic reaction.
EMEND for Injection may interact with some drugs including chemotherapy; therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products.
Patients on chronic warfarin therapy should be instructed to have their clotting status closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of fosaprepitant followed by aprepitant, with each chemotherapy cycle.
Administration of EMEND for Injection may reduce the efficacy of hormonal contraceptives. Patients should be advised to use alternative or back-up methods of contraception during treatment with EMEND for Injection and for 1 month following the last dose of the 3-day aprepitant regimen.
Drug Interactions
Drug interactions following administration of fosaprepitant are likely to occur with drugs that interact with oral aprepitant. The following information was derived from data with oral aprepitant and one study conducted with fosaprepitant and oral midazolam.
Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4 when administered as a 3-day antiemetic dosing regimen for CINV. Aprepitant is also an inducer of CYP2C9.
Effect of aprepitant on the pharmacokinetics of other agents
As a moderate inhibitor of CYP3A4, aprepitant can increase plasma concentrations of orally coadministered medicinal products that are metabolized through CYP3A4 (see CONTRAINDICATIONS).
Aprepitant has been shown to induce the metabolism of S(-) warfarin and tolbutamide, which are metabolized through CYP2C9. Coadministration of fosaprepitant or oral aprepitant with these drugs or other drugs that are known to be metabolized by CYP2C9, such as phenytoin, may result in lower plasma concentrations of these drugs.
Fosaprepitant or aprepitant is unlikely to interact with drugs that are substrates for the P-glycoprotein transporter, as demonstrated by the lack of interaction of oral aprepitant with digoxin in a clinical drug interaction study.
5-HT3 antagonists: In clinical drug interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron or hydrodolasetron (the active metabolite of dolasetron).
Corticosteroids:
Dexamethasone: Oral aprepitant, when given as a regimen of 125 mg with dexamethasone coadministered orally as 20 mg on Day 1, and oral aprepitant when given as 80 mg/day with dexamethasone coadministered orally as 8 mg on Days 2 through 5, increased the AUC of dexamethasone, a CYP3A4 substrate, by 2.2-fold on Days 1 and 5. The oral dexamethasone doses should be reduced by approximately 50% when coadministered with a regimen of fosaprepitant followed by aprepitant, to achieve exposures of dexamethasone similar to those obtained when dexamethasone is given without aprepitant. The daily dose of dexamethasone administered in clinical CINV studies with oral aprepitant reflects an approximate 50% reduction of the dose of dexamethasone (see DOSAGE AND ADMIN |
