Proton pump inhibitors and clopidogrel: is it a significant drug interaction?

Expert Opin Drug Saf. 2010 Jul;9(4):593-602. doi: 10.1517/14740331003645609.


Importance of the field: 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.

Areas covered in this review: 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.

What the reader will gain: 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.

Take home message: 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.

Publication types

  • Review

MeSH terms

  • Blood Platelets / drug effects
  • Clopidogrel
  • Drug Interactions
  • Drug Therapy, Combination / adverse effects
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / prevention & control
  • Humans
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / metabolism
  • Proton Pump Inhibitors / therapeutic use
  • Randomized Controlled Trials as Topic
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / metabolism
  • Ticlopidine / therapeutic use
  • Treatment Outcome


  • Gastrointestinal Agents
  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Ticlopidine