Drug Interactions between celecoxib and clopidogrel

MONITOR: Anticoagulants, antiplatelet agents, and thrombolytics may potentiate the risk of gastrointestinal bleeding complications associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors. A retrospective epidemiologic study of patients aged 65 years or older reported a nearly 13-fold increase in the risk of developing hemorrhagic peptic ulcer disease in concurrent users of oral anticoagulants and NSAIDs compared with nonusers of either drug. Fatalities have been reported.

MONITOR: A case of intracerebral hemorrhage occurred in an 86-year-old woman three weeks after starting therapy with celecoxib and clopidogrel. Both medications were stopped, and the patient recovered. Because intracerebral hemorrhage is a rather rare event with either drug alone, a drug interaction was suspected. However, the mechanism of interaction and a causal relationship have not been established. The investigators suggest a possible competitive inhibition of the CYP450 2C9 isoenzyme, resulting in increased plasma concentrations of one or both drugs.

MANAGEMENT: Although COX-2 inhibitors are often preferred over traditional, nonselective NSAIDs in patients who have increased risk for gastrointestinal toxicity, caution is advised during coadministration with anticoagulants or antiplatelet agents. Gastroprotective agents such as H2-receptor antagonists or proton pump inhibitors may be appropriate in high risk patients.