15 April 2010
Following an analysis of new data, the European Medicines Agency has recommended an amendment to the existing warning over the concomitant use of clopidogrel and proton-pump inhibitors (PPIs). The class warning for all PPIs has been replaced with a warning stating that only the concomitant use of clopidogrel and omeprazole or esomeprazole should be discouraged. For other PPIs, concomitant use can be considered if specifically indicated.
Healthcare professionals should continue to review the need for proton-pump inhibitor (PPI) therapy in patients who are receiving clopidogrel. Where concomitant use is considered essential, a PPI other than omeprazole or esomeprazole should be prescribed. The April Issue of Drug Safety Update included updated advice based on the EMEA report.
What is the recommendation based on?
Following the publication of observational studies suggesting that PPIs may reduce the effectiveness of clopidogrel by reducing its conversion into the active form, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended in May 2009 that the product information for all clopidogrel-containing medicines be amended to discourage the concomitant use of PPIs and clopidogrel unless absolutely necessary.
Since then, the CHMP has become aware of the results of a number of new studies, some of which put in question the clinical relevance of interactions between PPIs as a class and clopidogrel. However, two studies, completed at the end of August 2009, looked into the effect of omeprazole on the blood levels of the active form of clopidogrel. The studies confirmed that omeprazole can reduce the levels of the active form of clopidogrel in the blood and reduce its antiplatelet effects, therefore supporting the conclusion that there is an interaction between clopidogrel and omeprazole and esomeprazole.
Taking all of the currently available data into account, the CHMP and its Pharmacovigilance Working Party have concluded that there are no solid grounds to extend the warning to other PPIs. The class warning for all PPIs has been replaced with a warning stating that only the concomitant use of clopidogrel and omeprazole or esomeprazole should be discouraged.
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