Aspirin: Coadministration increased inhibition of ADP-induced ex vivo platelet aggregation when compared to aspirin alone.
Clopidogrel and other antiplatelet agents: Coadministration of clopidogrel did not have any effect on platelet count, prothrombin time, or activated partial thromboplastin time. Multiple doses of clopidogrel did not significantly increase steady state cilostazol plasma concentrations. Caution is advised when cilostazol is coadministered with any drug that inhibits platelet aggregation. Monitor the bleeding time at intervals. Cilostazol is contraindicated in patients receiving two or more additional antiplatelet/anticoagulant agents.
Warfarin and other anticoagulant agents: Cilostazol does not inhibit either the metabolism or pharmacologic effects (prothrombin time, activated partial thromboplastin time, bleeding time, platelet aggregation) of R- and S-warfarin after a single 25-mg dose of warfarin. Caution is advised in patients receiving both cilostazol and any anticoagulant agent. Frequent monitoring is required to reduce the possibility of bleeding. Cilostazol is contraindicated in patients receiving two or more additional antiplatelet/anticoagulant agents.
Strong inhibitors of CYP3A4: A priming dose of ketoconazole 400 mg was given one day prior to coadministration of single doses of ketoconazole 400 mg and cilostazol 100 mg. This regimen increased cilostazol Cmax by 94% and AUC by 117%. Other strong inhibitors of CYP3A4 (e.g., itraconazole, fluconazole, miconazole, fluvoxamine, fluoxetine, nefazodone, sertraline) would be expected to have a similar effect.
Moderate inhibitors of CYP3A4: Erythromycin and other macrolide antibiotics: Coadministration of erythromycin 500 mg every 8 hours with a single dose of cilostazol 100 mg increased cilostazol Cmax by 47% and AUC by 73%. Inhibition of cilostazol metabolism by erythromycin increased the AUC of 4'-trans-hydroxy-cilostazol by 141%. Other macrolide antibiotics would be expected to have similar effect.
Diltiazem: Decreased cilostazol clearance by about 30%; cilostazol Cmax and AUC increased by about 30% and 40%, respectively.
Grapefruit juice: Increased cilostazol Cmax by about 50% but had no effect on AUC.
Inhibitors of CYP2C19: Omeprazole: Coadministration of omeprazole did not significantly affect cilostazol metabolism, but the systemic exposure to 3,4-dehydro-cilostazol was increased by 69%, probably the result of omeprazole's potent inhibition of CYP2C19.
Quinidine: Did not alter cilostazol pharmacokinetics.
Lovastatin: Decreased cilostazol Css,max and AUC by 15% and cilostazol metabolite concentrations (although nonsignificant); increased lovastatin and beta-hydroxy-lovastatin AUC by about 70%.
Inducers of CYP3A4 and CYP2C19 (e.g., carbamazepine, phenytoin, rifampicin, St. John's wort): The antiplatelet effect may be altered and should be carefully monitored.