Cilostazol drug interactions: Difference between revisions

Revision as of 16:21, 28 February 2014

Cilostazol
PLETAL^® FDA Package Insert
Indications and Usage
Dosage and Administration
Contraindications
Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Studies
Clinical Pharmacology
Nonclinical Toxicology
How Supplied/Storage and Handling
Patient Counseling Information
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]

Cilostazol Drug Interactions

Aspirin

Short-term (≤4 days) coadministration of aspirin with PLETAL increased the inhibition of ADP-induced ex vivo platelet aggregation by 22%-37% when compared to either aspirin or PLETAL alone. Short-term (≤4 days) coadministration of aspirin with PLETAL increased the inhibition of arachidonic acid-induced ex vivo platelet aggregation by 20% compared to PLETAL alone and by 48% compared to aspirin alone. However, short-term coadministration of aspirin with PLETAL had no clinically significant impact on PT, aPTT, or bleeding time compared to aspirin alone. Effects of long-term coadministration in the general population are unknown. In eight randomized, placebo-controlled, double-blind clinical trials, aspirin was coadministered with cilostazol to 201 patients. The most frequent doses and mean durations of aspirin therapy were 75-81 mg daily for 137 days (107 patients) and 325 mg daily for 54 days (85 patients). There was no apparent increase in incidence of hemorrhagic adverse effects in patients taking cilostazol and aspirin compared to patients taking placebo and equivalent doses of aspirin.

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 PLETAL on the pharmacokinetics and pharmacodynamics of both drugs is unknown.

Clopidogrel

Multiple doses of clopidogrel do not significantly increase steady state plasma concentrations of cilostazol.

Inhibitors of CYP3A4

Strong Inhibitors of CYP3A4

A priming dose of ketoconazole 400 mg (a strong inhibitor of CYP3A4), was given one day prior to coadministration of single doses of ketoconazole400 mg and cilostazol 100 mg. This regimen increased cilostazol Cmax by 94% and AUC by 117%. Other strong inhibitors of CYP3A4, such as itraconazole, fluconazole, miconazole, fluvoxamine, fluoxetine, nefazodone, and sertraline, would be expected to have a similar effect (see DOSAGE AND ADMINISTRATION).

Moderate Inhibitors of CYP3A4

Erythromycin and othermacrolide antibiotics: Erythromycin is a moderately strong inhibitor of CYP3A4. Coadministration of erythromycin500 mg q 8h 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 (e.g., clarithromycin), but not all (e.g., azithromycin), would be expected to have a similar effect (see DOSAGE AND ADMINISTRATION). Diltiazem: Diltiazem 180 mg decreased the clearance of cilostazol by ~30%. Cilostazol Cmax increased ~30% and AUC increased ~40% (see DOSAGE AND ADMINISTRATION). Grapefruit Juice: Grapefruit juice increased the Cmax of cilostazol by ~50%, but had no effect on AUC.

Inhibitors of CYP2C19

Omeprazole

Coadministration of omeprazole did not significantly affect the metabolism of cilostazol, but the systemic exposure to 3,4-dehydro-cilostazol was increased by 69%, probably the result of omeprazole's potent inhibition of CYP2C19 (see DOSAGE AND ADMINISTRATION).

Quinidine

Concomitant administration of quinidine with a single dose of cilostazol 100 mg did not alter cilostazol pharmacokinetics.

Lovastatin

The concomitant administration of lovastatin with cilostazol decreases cilostazol Css, max and AUCτ by 15%. There is also a decrease, although nonsignificant, in cilostazol metabolite concentrations. Coadministration of cilostazol with lovastatin increases lovastatin and β-hydroxi lovastatin AUC approximately 70%. This is most likely clinically insignificant.

Major Interactions

Moderate Interactions

Minor Interactions

Adapted from the FDA Package Insert.

References

http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=24d75b58-bafb-4440-b8d7-4f4079c08b0b

@@ Line 42: / Line 42: @@
 ''Lovastatin''
-The concomitant administration of [[lovastatin ]]with cilostazol decreases cilostazol Css, max and AUCτ by 15%. There is also a decrease, although nonsignificant, in cilostazol metabolite concentrations. Coadministration of cilostazol with [[lovastatin ]]increases lovastatin and β-hydroxi lovastatin AUC approximately 70%. This is most likely clinically insignificant.
+The concomitant administration of [[lovastatin ]]with cilostazol decreases cilostazol Css, max and AUCτ by 15%. There is also a decrease, although nonsignificant, in cilostazol metabolite concentrations. Coadministration of cilostazol with [[lovastatin]] increases lovastatin and β-hydroxi lovastatin AUC approximately 70%. This is most likely clinically insignificant.
 ===Major Interactions===

Cilostazol drug interactions: Difference between revisions

Revision as of 16:21, 28 February 2014