PIC QUESTION OF THE WEEK: 2/09/09 

Q: What is the significance of the possible drug interaction between clopidogrel and proton pump inhibitors?

Update

This Update is provided because of some recent literature suggesting the potential drug interaction between Clopidogrel - PPIs discussed in the 2/09/2009 PIC Question of the Week may be more significant than initially suggested. A number of studies published in 2009 have directly or indirectly evaluated P-450 2C19 enzyme activity and patient response to clopidogrel and PPIs. It appears that patients receiving clopidogrel have a greater tendency toward cardiovascular (CV) events if they possess a less active genetic variant of 2C19. In one of the studies, concomitant use of PPIs had no effect on CV events. In another, there was an increase in the number of CV events in those receiving PPIs, but not among patients treated with pantoprazole. The Medical Letter on Drugs and Therapeutics has recently published an addendum to its earlier review of the topic and also advised that the interaction may be important. It appears that histamine H2-antagonists might be preferable to PPIs in patients receiving clopidogrel. The significance of the interaction between PPIs and clopidogrel does require further study. Supportive references are included below. References:

• Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-62.

• Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:363-75.

• PPI interactions with clopidogrel – revisited. Med Lett Drugs Ther 2009;51:13. • Juurlink DN, Gomes T, Ko D, et al. A population-based study of the drug interaction between proton pump

inhibitors and clopidogrel. CMAJ 2009;180(7). DOI:10.1503/cmaj.o82001 John G. Lech, Pharm.D. The PIC Question of the Week is a publication of the Pharmaceutical Information Center, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282 (412.396.4600).

Dick LeBeau – Defensive Coordinator, Super Bowl Steelers-2009