Potential interaction between clopidogrel and proton pump inhibitors
05.06.2009
The European Medicines Agency (EMEA) published a statement on potential interaction between clopidogrel and proton pump inhibitors. In patients simultaneously taking clopidogrel and a proton pump inhibitor, the effect of clopidogrel may be reduced, which may result in an increased risk of, for instance, heart attack and cerebral thrombosis, or the coronary stent and bypass thrombosis.
Clopidogrel is approved in indications for prevention of atherothrombotic events in patients who had a heart attack or an ischemic stroke, those with peripheral arterial disease and in patients suffering from an acute coronary syndrome, including the patients undergoing stent implantation after a percutaneous coronary intervention. In the Republic of Croatia, it is primarily used as part of an antithrombotic therapy after a coronary stent implantation and after a coronary bypass implantation in line with professional guidelines.
Proton pump inhibitors are indicated for treatment and prevention of gastro-oesophageal reflux disease, dyspepsia, and stomach and duodenal ulcer.
Clopidogrel may cause disorders of the digestive system (e.g. adverse reactions include dyspepsia, nausea, gastritis, ulcer etc.), which is why it is often prescribed together with a proton pump inhibitor.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency evaluated the results of 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 proton pump inhibitors class of medicines, making clopidogrel less effective when given with these medicines. Therefore, a concomitant use of proton pump inhibitors and clopidogrel is not recommended, unless it is necessary.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency have recommended that the product information for all clopidogrel-containing medicines should be amended to discourage concomitant use of proton pump inhibitors and clopidogrel-containing medicines unless absolutely necessary. After the proposed measures will have been approved in the European Union, the Summary of Product Characteristics and the Patient Information Leaflet approved in the Republic of Croatia will be amended as well.
Recommendations for healthcare professionals:
- Upon the next visit, to review the need for proton pump inhibitor therapy in patients already taking clopidogrel; prescribe these medicines at the same time only when necessary;
- Check whether any patients taking clopidogrel are taking a proton pump inhibitor on their own initiative.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommended that further information is needed in relation to the inhibition of clopidogrel metabolism by other medicines, and in relation to the implications of genetic variation which results in a small proportion of individuals (so called "CYP2C19 poor metabolisers”) being unable to fully convert clopidogrel to its active form, regardless of interaction with other medicines.
The Agency for Medicinal Products and Medical Devices sent a Dear Healthcare Professional Letter to prescribing physicians providing important safety information about the potential interaction between clopidogrel and proton pump inhibitors.
The Agency for Medicinal Products and Medical Devices of the Republic of Croatia carefully monitors the safe use of this class of medicinal products and reminds of the adverse reaction reporting obligation.
The text of the letter to physicians can be found at the following link: Dear Healthcare Professional Letter [pdf; 539KB]
EMEA statement can be found at the following link:
http://www.emea.europa.eu/humandocs/PDFs/EPAR/Plavix/32895609en.pdf
