Interactions between alosetron and Emend 3 day (aprepitant)
alosetron and aprepitant (Moderate Drug-Drug)
MONITOR: Coadministration with aprepitant or its prodrug, fosaprepitant, may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 2C9. The mechanism is accelerated clearance due to induction of CYP450 2C9 activity by aprepitant. According to the manufacturer, coadministration of aprepitant (125 mg single dose on day 1 and 80 mg/day on days 2 and 3) and the 2C9 substrate tolbutamide (500 mg orally prior to initiation of aprepitant and on days 4, 8 and 15) resulted in a reduction in the area under the plasma concentration-time curve (AUC) of tolbutamide by 23% on day 4, 28% on day 8, and 15% on day 15. Similarly, healthy subjects stabilized on chronic warfarin therapy given the same regimen of aprepitant had a 34% decrease in S(-) warfarin trough concentration accompanied by a 14% decrease in the INR five days after completion of aprepitant dosing. However, there was no effect on the systemic exposure (AUC) of R(+) and S(-) warfarin determined on day 3.
MANAGEMENT: Caution is advised if aprepitant or fosaprepitant must be used concomitantly with medications that undergo metabolism by CYP450 2C9, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever aprepitant or fosaprepitant is added to or withdrawn from therapy.
