Drug Interaction Report

MONITOR: Coadministration with aprepitant or its prodrug, fosaprepitant, may increase the plasma concentrations of chemotherapeutic agents that are primarily metabolized by CYP450 3A4. The proposed mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by aprepitant. In premarketing clinical studies, aprepitant was administered commonly with etoposide, vinorelbine or paclitaxel, although dosages of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies, aprepitant had no effect on the pharmacokinetics of docetaxel or vinorelbine, both of which are substrates of CYP450 3A4. However, an interaction has been demonstrated with the probe CYP450 3A4 substrate, midazolam. In general, the effect of aprepitant on the pharmacokinetics of CYP450 3A4 substrates is expected to be greater when the substrates are administered orally as opposed to intravenously and may be altered following prolonged administration.

MANAGEMENT: Caution is advised if aprepitant or fosaprepitant is administered with chemotherapeutic agents that are primarily metabolized by CYP450 3A4, particularly those that were not studied extensively in premarketing trials. The potential for increased systemic toxicities of these agents should be considered. Chronic, continuous use of aprepitant for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during long-term use.