EMEA warns of possible interaction between clopidogrel and PPIs

Br J Cardiol 2009;16:163-6 Leave a comment
Click any image to enlarge

The European Medicines Agency (EMEA) has issued a warning about a possible interaction between clopidogrel and proton-pump inhibitors (PPIs), such as omeprazole, which are taken for gastric problems. The EMEA has recommended that the product information for all clopidogrel-containing medicines be amended to discourage concomitant use of PPIs unless absolutely necessary.

The UK Medicines and Healthcare Products Regulatory Agency (MHRA), has also issued advice to GPs that concomitant use of a PPI with clopidogrel is not recommended unless considered essential, urging a review of the prescribing of PPIs at the next appointment for patients taking clopidogrel.

The EMEA statement points out that, as heartburn and stomach ulcers can occur as side-effects of clopidogrel, patients taking clopidogrel often take PPIs to prevent or ease these symptoms. It is estimated that around 500,000 patients in the UK are currently prescribed clopidogrel and around half are also prescribed PPIs. Many more may be buying omeprazole over the counter. Other PPIs include esomeprazole, lansoprazole, pantoprazole, and rabeprazole.

EMEA says concern about a possible interaction comes from several recently published studies examining clinical outcomes of clopidogrel users. “Taken together, these studies suggest that a significant interaction might occur between clopidogrel and members of the PPI class of medicines, making clopidogrel less effective when given with these medicines”, the statement says. “One possible explanation for this observation is that some PPIs prevent the conversion of clopidogrel into its biologically active form in the body, reducing the effectiveness of clopidogrel and increasing the risk of heart attack or other conditions involving harmful clotting (e.g. strokes). However, as different PPIs have different capacity to affect the metabolism of clopidogrel and as the outcome studies have not fully reflected the different effect of PPIs on activation of clopidogrel, there may be more than one explanation for the effect of this class of medicines on clopidogrel,” it adds.