Clinical evidence of interaction between clopidogrel and proton pump inhibitors

Abstract

Clopidogrel is approved for reduction of atherothrombotic events in patients with cardiovascular (CV) and cerebrovascular disease. Dual antiplatelet therapy with aspirin and clopidogrel decreases the risk of major adverse cardiac events after acute coronary syndrome or percutaneous coronary intervention, compared with aspirin alone. Due to concern about gastrointestinal bleeding in patients who are receiving clopidogrel and aspirin therapy, current guidelines recommend combined use of a proton pump inhibitor (PPI) to decrease the risk of bleeding. Data from previous pharmacological studies have shown that PPIs, which are extensively metabolized by the cytochrome system, may decrease the ADP-induced platelet aggregation of clopidogrel. Results from retrospective cohort studies have shown a higher incidence of major CV events in patients receiving both clopidogrel and PPIs than in those without PPIs. However, other retrospective analyses of randomized clinical trials have not shown that the concomitant PPI administration is associated with increased CV events among clopidogrel users. These controversial results suggest that large specific studies are needed. This article reviews the metabolism of clopidogrel and PPIs, existing clinical data regarding the interaction between clopidogrel and PPIs, and tries to provide recommendations for health care professionals.

Retrospective Analysis of Potential Adverse Drug Interactions in the Drugs Prescribed to the Elderly at a Tertiary Health Care Center in Raipur, Chhattisgarh, Central India

“…The significance mentioned is, 'the individual patient's risk factors for gastrointestinal bleeding should be considered against the possible risk of an interaction with clopidogrel, to consider the use of an alternative antiplatelet agent free of interaction with proton pump inhibitors, if their use is essential.' Lin et al in their study suggested a recommendation to separate these two drugs with a gap of 12-15 h to prevent any competitive inhibition and suggested taking PPI before breakfast and clopidogrel at bedtime [16].…”

Evaluation of inappropriate prescribing to the hospitalized elderly patients in Al Shifa hospital, Gaza, Palestine

“…Omeprazole decreases the effect of clopidogrel by inhibiting the hepatic enzyme CYP2C19 metabolism, and thus decreasing the formation of the active antiplatelet metabolite. 17,24 Pantoprazole 25 and famotidine 26 can be alternatives to omeprazole to be used with clopidogrel.…”

The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study

“…In addition, overuse of these medications for nonindicated conditions is prevalent [12,13]. These medications are generally well tolerated and have traditionally been considered relatively safe and free from adverse effects; although more recently, there have been reports linking PPIs with Clostridium difficile-associated diarrhea, hypomagnesemia, increased cardiovascular events in cardiac patients on clopidogrel, and pneumonia [14][15][16][17]. Due to the high prevalence of PPI use and the impact of osteoporosis-related fractures on health and quality of life, evidence of even a moderate association between these medications and fragility fractures would have important health implications.…”