Drug Interaction Report

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.

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 proton pump inhibitors or misoprostol may be appropriate in high risk patients.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of cilostazol. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Until more information is available, the manufacturer recommends avoiding consumption of grapefruit juice during cilostazol therapy. Orange juice is not expected to interact with cilostazol.