Aprepitant modestly reduces warfarin levels and slightly decreases INR in healthy subjects
Clinical evidence,mechanism, importance and management
In a double-blind study,healthy subjects were stabilised on warfarin and then given either aprepitant (125 mg on day one, then 80mg daily on days 2 and 3) or placebo. On day 3,there was no change in warfarin levels. However, by day 8 (5 days after stopping aprepitant) there was a 34 % decrease in trough S-warfarin levels, and a 14 % decrease in INR in aprepitant group (See reference number 1).
Aprepitant is an inducer of cytochrome P450 isoenzyme CYP2C9, by which S-warfarin is metabolised. The manufacturer recommends that, in patients taking warfarin, INR should be monitored closely for 2 weeks, particularly at 7 to 10 days,(See reference number 2) after each 3-day course of aprepitant,(See reference number 2,3) and this seems a prudent precaution. They similarly recommend caution with acenocoumarol,which is also metabolised by CYP2C9 (See reference number 3).
1. Depré M,Van Hecken A, Oeyen M, De Lepeleire I, Laethem T, Rothenberg P, Petty KJ, Majumdar A, Crumley T, Panebianco D, Bergman A, de Hoon JN. Effect of aprepitant on thepharmacokinetics and pharmacodynamics of warfarin. Eur J Clin Pharmacol (2005) 61, 341–
6.
Emend (Aprepitant). Merck & Co.,Inc. US Prescribing information, June 2006.
Emend (Aprepitant). Merck Sharp & Dohme Ltd. UK Summary of product characteristics,February 2007.