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06-04-2010 | Cardiology | Article

UK drug regulatory body modifies clopidogrel-PPI advice


MHRA Drug Safety Update April 2010

MedWire News: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has modified the advice it published in a statement in May last year regarding concomitant use of clopidogrel with proton pump inhibitors (PPIs).

Use of either omeprazole or esomeprazole with clopidogrel should be discouraged, but current evidence does not support extending this advice to other PPIs, states the MHRA in its April 2010 Drug Safety Update newsletter.

“In light of the most recent evidence, the previous advice (to avoid all PPIs unless absolutely necessary for patients taking clopidogrel) is no longer considered necessary,” the report explains. “Nevertheless, as a precaution, concomitant use of clopidogrel with omeprazole or esomeprazole should be discouraged.”

The updated advice reflects the European Medicines Agency’s stance, outlined in a public statement last month.

Some cardiologists expressed concern at last year’s public warning from the MHRA and the European and US drug regulatory bodies that concomitant use of PPIs with clopidogrel should be avoided, as reported in MedWire News coverage.

The directive was based on pharmacokinetic and pharmacodynamic data demonstrating the potential for PPIs that competitively inhibit the CYP2C19 isoenzyme – which metabolizes clopidogrel to its active form – to attenuate the inhibition of platelet aggregation by clopidogrel, as well as limited, observational clinical outcomes data.

Since then, new evidence has become available that “casts some doubt on the clinical relevance of possible interactions between clopidogrel and PPIs,” the MHRA says.

This evidence includes post hoc analyses of the PRINCIPLE-TIMI and TRITON-TIMI trials finding (unspecified) PPI use in patients randomly assigned to clopidogrel did not affect the clinical outcome, and the COGENT randomized trial which found no effect of concomitant omeprazole with clopidogrel on cardiovascular outcome.

The MHRA says information for prescribers and patients will be updated with the latest advice.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Caroline Price


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