Proton pump inhibitors and clopidogrel: is it a significant drug interaction?
BACKGROUND
Clopidogrel is indicated as part of a dual antiplatelet therapy (DAT) with aspirin for the prevention of cardiac related events in acute coronary syndromes particularly in patients undergoing percutaneous coronary intervention. Recently, there have been reports of a clinically significant drug interaction between clopidogrel and proton pump inhibitors (PPI), which are frequently co-prescribed to prevent DAT associated gastrointestinal (GI) bleeding.


METHODS
This review evaluates the risk of GI bleeding associated with DAT and the rationale for the use of PPI. This review also describes the pharmacokinetic and pharmacodynamic basis for the interaction and evaluates its significance on clinical outcomes. An extensive literature search on PubMed from January 1980 to August 2009 was performed. Additionally, abstracts and presentations from key cardiology meetings and press releases were reviewed for relevant studies related to the interaction.


RESULTS
At the end of the review, readers should have a complete understanding of the interaction and steps that can be taken to limit the interaction.


CONCLUSIONS
There is a mechanistic basis and pharmacodynamic data supporting an interaction between PPIs, particularly omeprazole and clopidogrel. The clinical significance of this interaction is, however, still a subject of intense debate and ongoing research.
Oyetayo
Ola O
OO
University of Texas Health Science Center, Pharmacotherapy Education and Research Center, School of Medicine, 7703 Floyd Curl Drive, MC 6220, San Antonio, TX 78229, USA. oyetayo@uthscsa.edu
Talbert
Robert L
RL
D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005765:Gastrointestinal Agents / Q000009:adverse effects; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D016896:Treatment Outcome
D005765:Gastrointestinal Agents; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine