Bestazol 50/Bestazol 100 Drug Interactions

Cilostazol could have pharmacodynamic interactions with other inhibitors of platelet function and pharmacokinetic interactions because of effects of other drugs on its metabolism by CYP3A4 or CYP2C19.
Aspirin: Coadministration of aspirin with cilostazol increased the inhibition of platelet aggregation compared to either product alone. Coadministration had no clinically significant impact on PT, aPTT or bleeding time.
HMG-CoA reductase inhibitors (i.e., simvastatin, lovastatin): Cilostazol may inhibit the metabolism (CYP3A4) of certain HMG-CoA reductase inhibitors. Plasma concentrations of certain HMG-CoA reductase inhibitors may be elevated by cilostazol, increasing the therapeutic and adverse reactions.
Lovastatin: The coadministration of lovastatin with cilostazol decreased cilostazol C_{ss, max} and AUC by 15%. There is also a decrease, although nonsignificant, in cilostazol metabolite concentrations. Coadministration increases lovastatin AUC by approximately 70%.
Warfarin: The cytochrome P-450 isoenzymes involved in the metabolism of R-warfarin are CYP3A4, CYP1A2 and CYP2C19, and in the metabolism of S-warfarin, CYP2C9. Cilostazol did not inhibit either the metabolism or the pharmacologic effects (PT, aPTT, bleeding time, or platelet aggregation) of R- and S-warfarin after a single 25 mg dose of warfarin. The effect of concomitant multiple dosing of warfarin and cilostazol on the pharmacokinetics and pharmacodynamics of both drugs is unknown.
Clopidogrel: Additive effects on bleeding times not determined.
Caution is advised and bleeding times should be monitored during such concomitant therapy.
Drugs that inhibit or are substrates for CYP3A4: Potential pharmacokinetic interaction (increased plasma cilostazol concentrations, decreased clearance) with other inhibitors of CYP3A4 isoenzyme, including certain azole antifungals (e.g., fluconazole, itraconazole, ketoconazole, miconazole), certain macrolide antibiotics (e.g., erythromycin or clarithromycin but not azithromycin), certain selective serotonin-reuptake inhibitors (e.g., fluoxetine, fluvoxamine, nefazodone, sertraline), certain antiretroviral agents (e.g., indinavir), metronidazole, diltiazem and danazol.
Erythromycin or other macrolide antibiotics: Certain macrolide antibiotics may inhibit the metabolism (CYP3A4) of cilostazol. Erythromycin decreases the metabolism of cilostazol through inhibition of the CYP3A4 isoenzyme; similar effects are expected from other macrolide antibiotics. Cilostazol plasma concentrations may be elevated, increasing the therapeutic and adverse effects.
It may be necessary to decrease the dose of cilostazol during coadministration of certain macrolide antibiotics. Consider a dosage of cilostazol 50 mg twice daily in patients receiving one of these macrolide antibiotics.
Diltiazem: Cilostazol plasma concentrations are increased by diltiazem. Diltiazem 180 mg decreased the clearance of cilostazol by approximately 30% and increased the C_max and AUC approximately 30% and 40%, respectively.
Quinidine: Concomitant administration of quinidine with a single dose of cilostazol 100 mg did not alter cilostazol pharmacokinetics.
Omeprazole: Omeprazole may inhibit the metabolism (CYP2C19) of cilostazol. Cilostazol plasma concentrations may be elevated, increasing the therapeutic and adverse effects.
It may be necessary to decrease the dose of cilostazol during coadministration of omeprazole. Consider a dosage of cilostazol 50 mg twice daily in patients receiving omeprazole.
Ginkgo biloba: Ginkgo biloba does not appear to affect the antiplatelet activity of cilostazol. However, bleeding time may be prolonged by additive or synergistic effect.
Food: Grapefruit juice increased the C_max of cilostazol by approximately 50%, but had no effect on AUC. A high-fat meal increases absorption with an approximately 90% increase in C_max and a 25% increase in the AUC.
Smoking, tobacco: Systemic cilostazol exposure is decreased by approximately 20% in association with tobacco smoking.