Drug-drug interaction between clopidogrel and the proton pump inhibitors.
OBJECTIVE
To evaluate the interaction between clopidogrel and proton pump inhibitors (PPIs).


METHODS
Literature retrieval was accessed through PubMed (1980-January 2009), abstracts from 2008 American Heart Association and 2009 Society of Cardiovascular Angiography and Interventions Scientific Sessions, and media press releases using the terms clopidogrel, proton pump inhibitors, cytochrome 2C19, genetic cytochrome P450 polymorphisms, and drug interaction. In addition, reference citations from publications identified in the search were reviewed.


METHODS
Relevant original research articles and review articles were evaluated. Articles were selected if they were published in English and focused on any of the key words or appeared to have substantial content addressing the drug interaction.


RESULTS
Recent attention has been placed on a potential interaction observed between clopidogrel and the widely used PPIs. Preliminary evidence suggests that omeprazole interacts with clopidogrel, reducing clopidogrel's antiplatelet effects as measured by various laboratory tests. Most data indicate that the interaction involves the competitive inhibition of the CYP2C19 isoenzyme. The interaction appears to be clinically significant, as several retrospective analyses have shown an increase in adverse cardiovascular outcomes when PPIs and clopidogrel are used concomitantly. However, this may not be a class effect.


CONCLUSIONS
Available data suggest that omeprazole is the PPI most likely to have a significant interaction with clopidogrel. Further studies are needed to determine that an interaction between the other PPIs and clopidogrel does not exist. In situations in which both clopidogrel and a PPI are indicated, pantoprazole should be used since it is the PPI least likely to interact with clopidogrel.
Norgard
Nicholas B
NB
School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA. nnorgard@buffalo.edu
Mathews
Kathryn D
KD
Wall
Geoffrey C
GC
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000009:adverse effects / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D006801:Humans; D009853:Omeprazole / Q000009:adverse effects / Q000494:pharmacology; D000077402:Pantoprazole; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D013988:Ticlopidine