In May 2009, the EU Committee for Medicinal Products for Human Use (CHMP) issued guidance stating that the co-prescribing of clopidogrel and all proton pump inhibitors (PPIs) should be avoided unless considered essential and that patients receiving the combination should have their treatment reviewed.
The manufacturers of clopidogrel updated their product information on the basis of pharmacokinetic, pharmacodynamic and some clinical outcome data, which demonstrated that omeprazole inhibits the CYP2C19 isoenzyme and as a result reduces the ability of clopidogrel to inhibit platelet aggregation, thereby reducing the drug's beneficial effects.
At the time the advice was extended to cover the whole PPI class; however, since then new evidence has become available which despite having limitations has caused the CHMP to amend their advice.
The updated advice for healthcare professionals states that:
- Concomitant use of clopidogrel and omeprazole or esomeprazole is to be avoided unless considered essential.
- Prescribers should check that patients prescribed clopidogrel are not buying over-the-counter omeprazole.
- Pharmacists should check whether patients buying omeprazole are taking clopidogrel.
- PPIs other than omeprazole or esomeprazole; H2 blockers; or antacids should be considered in patients taking clopidogrel.
- Use of other known CYP2C10-inhibiting medicines with clopidogrel is discouraged as they are expected to have a similar effect as omeprazole and esomeprazole.