Pletaal Drug Interactions

Food effect: A high-fat meal increased absorption of cilostazol, with an approximately 90% increase in Cmax and a 25% increase in AUC.
Clopidogrel: Coadministration significantly increased AUC of dehydro-cilostazol metabolite by 24%. Although it cannot be determined whether there was an additive effect on bleeding times during concomitant administration with cilostazol and clopidogrel, caution is advised for checking bleeding times at intervals during coadministration of cilostazol and clopidogrel.
Aspirin: Short term (≤4 days) co-administration of Pletaal and aspirin resulted in small increases of plasma levels of cilostazol and its active metabolites together with 23-37% increase in inhibition of ADP induced ex vivo platelet aggregation compared to that obtained with either aspirin or Pletaal alone.
Short term (≤4 days) co-administration of aspirin with Pletaal increased the inhibition of arachidonic acid-induced ex vivo platelet aggregation by 20% compared to Pletaal alone, and by 48% compared to aspirin alone. However, short-term (≤4 days) co-administration of aspirin with Pletaal had no clinically significant impact on PT, PTT, or bleeding time compared to aspirin alone.
Warfarin: The pharmacokinetics and the effects on prothrombin time of a single 25mg dose of warfarin were not affected by twice daily administration of Pletaal 100mg. However, caution is advised in patients receiving both cilostazol and any anticoagulant agent.
Cytochrome P-450 (CYP) Enzyme Inhibitors: Cilostazol is extensively metabolized by hepatic cytochrom P450 (CYP) enzymes, mainly CYP3A4, and to lesser extent by CYP2C19. Inhibitors of CYP3A4, such as itraconazole, erythromycin, diltiazem, and ketoconazole; and the inhibitors of CYP2C19 such as omeprazole, have been shown to increase blood levels of cilostazol and / or its metabolites. Cilostazole had little effect on blood levels of lovastatin which is highly sensitive to CYP3A4 inhibition.
CYP3A4 Inhibitors: Grapefruit juice: Administration of a single dose of 100mg cilostazol with 240mL grapefruit juice (an inhibitor of intestinal CYP3A4) did not have a notable effect on the pharmacokinetics of cilostazol. Based on these data, no dose adjustment is necessary. A clinically relevant effect on cilostazol is still possible at higher quantities of grapefruit juice.
Ketoconazole: Co-administration of ketonazole (an inhibitor of CYP3A4) with cilostazol resulted in a 117% increase in the AUC of cilostazol, accompanied by a 15% decrease in the AUC of the dehydro metabolite and an 87% increase in the AUC of the 4'-trans-hydroxy metabolite. Based on AUC, the overall pharmacological activity of cilostazol increases 35% when co-administered with ketoconazole. Based on these data, the recommended dose of cilostazol is 50mg bid in the presence of ketoconazole and similar agents (e.g., intraconazole).
Diltiazem: Administration of cilostazol with diltiazem resulted in an increase in the AUC of cilostazol by 44%, accompanied by a 4% increase in AUC of the dehydro metabolite and a 43% increase in the AUC of the 4'-trans-hydroxy metabolite.
Based on AUC, overall pharmacological activity of cilostazol increases by 19% when co-administered with diltiazem. Based on these data, the recommended dose of cilostazol is 50mg bid in the presence of diltiazem.
Erythromycin: Administration of cilostazol with erythromycin resulted in an increase in the AUC of cilostazol by 72%, accompanied by a 6% increase in AUC of the dehydro metabolite and a 119% increase in AUC of the 4'-trans-hydroxy metabolite. Based on AUC, the overall pharmacological activity of cilostazol increases by 34% when co-administered with erythromycin. Based on these data, the recommended dose of cilostazol is 50mg bid in the presence of erythromycin and similar agents (e.g., clarithromycin).
CYP2C19 Inhibitors: Omeprazole: Administration of cilostazol with omeprazole (an inhibitor of CYP2C19) increased the AUC of cilostazol by 22%, accompanied by a 68% increase in the AUC of the dehydro metabolite and a decrease of 36% in the AUC of the 4'-trans hydroxyl metabolite. Based on AUC, the overall pharmacological activity increases by 47% when co-administered with omeprazole. Based on these data, the recommended dose of cilostazol is 50mg bid in the presence of omeprazole.
CYP2D6 Inhibitors: Quinidine: (CYP2D6 inhibitor) A 200mg single dose of quinidine had no significant effect on the pharmacokinetics of a single 100mg dose of cilostazol.