Cilostazol (
Pletal) is a selective inhibitor of
phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. It also exhibits antiproliferative effects on smooth muscle cells and has beneficial effects on
high density lipoprotein-cholesterol and
triglyceride levels.Randomized, double-blind, placebo-controlled 12- to 24-week trials in >2000 patients with moderate to severe
intermittent claudication demonstrated that
cilostazol generally significantly increased walking distances and improved quality of life compared with placebo. Additionally, a large comparative 24-week trial showed that
cilostazol 100 mg twice daily was significantly more effective than
pentoxifylline 400mg three times daily (
pentoxifylline was not significantly different from placebo).
Cilostazol was generally well tolerated. Adverse events reported significantly more often with
cilostazol than with placebo included
headache,
diarrhea, abnormal stools,
infection,
rhinitis and peripheral
edema and in comparison with
pentoxifylline were
headache,
diarrhea, abnormal stools and palpitations. Adverse events were generally mild to moderate in intensity, transient or resolved after symptomatic treatment and rarely required treatment withdrawal. Significant drug interactions are observed when
cilostazol is coadministered with other agents that inhibit
cytochrome P450 (CYP) 3A4 (e.g.
erythromycin or
diltiazem) or
CYP2C19 (e.g.
omeprazole). As a result, in Europe
cilostazol is contraindicated in patients receiving
CYP3A4 or
CYP2C19 inhibitors and in the US it is recommended that dosage reduction for
cilostazol be considered during coadministration of
cilostazol and
CYP3A4 or
CYP2C19 inhibitors. Conversely,
cilostazol itself does not appear to inhibit
CYP3A4. Coadministration of
cilostazol with
aspirin or
warfarin did not result in any clinically significant changes to coagulation parameters, bleeding time or platelet aggregation.
CONCLUSION: