Aprepitant in antiemetic combinations to prevent chemotherapy-induced nausea and vomiting.

Abstract

Aprepitant is an oral neurokinin-1 receptor antagonist which acts centrally to block chemotherapy-induced emesis. Its main pathway of elimination is by the cytochrome p450 isozyme CYP3A4, which is the basis for drug interactions with dexamethasone and oral contraceptives. Aprepitant is well tolerated, and phase II trials in high-dose cisplatin-induced emesis showed that it is most effective when 125 mg orally is added to a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone for acute emesis and then an 80 mg oral dose continued with dexamethasone on days 2 and 3 to prevent delayed emesis. Two pivotal phase III trials enrolling a total of 1099 patients showed that the complete control of emesis improved by 20% in patients receiving aprepitant as compared with standard therapy, with the most impressive differences being in delayed emesis. Control was maintained over multiple cycles and occurred in both males and females and young and old adults.