DailyMed Label: Cilostazol

DailyMed Label: CILOSTAZOL

2010

DailyMed Prescription

CILOSTAZOL

CILOSTAZOL

STAT RX USA LLC

NDC: 16590-285

NDC: 16590-285

DESCRIPTION Cilostazol is a quinolinone derivative that inhibits cellular phosphodiesterase (more specific for phosphodiesterase III). The empirical formula of cilostazol is C 20 H 27 N 5 O 2 , and its molecular weight is 369.46. Cilostazol is 6-[4-(1-cyclohexyl-1 H -tetrazol-5-yl)butoxy]-3,4-dihydro-2(1 H )-quinolinone, CAS-73963-72-1. The structural formula is: Cilostazol occurs as white to off-white crystals or as a crystalline powder that is slightly soluble in methanol and ethanol, and is practically insoluble in water, 0.1 N HCl, and 0.1 N NaOH. Cilostazol tablets for oral administration are available as 50 mg or 100 mg round, white debossed tablets. Each tablet, in addition to the active ingredient, contains the following inactive ingredients: carboxymethylcellulose calcium, corn starch, hypromellose, magnesium stearate and microcrystalline cellulose. Chemical Structure

Cilostazol tablets are indicated for the reduction of symptoms of intermittent claudication, as indicated by an increased walking distance.

DOSAGE AND ADMINISTRATION The recommended dosage of cilostazol is 100 mg b.i.d. taken at least half an hour before or two hours after breakfast and dinner. A dose of 50 mg b.i.d. should be considered during coadministration of such inhibitors of CYP3A4 as ketoconazole, itraconazole, erythromycin and diltiazem, and during coadministration of such inhibitors of CYP2C19 as omeprazole. Patients may respond as early as 2 to 4 weeks after the initiation of therapy, but treatment for up to 12 weeks may be needed before a beneficial effect is experienced. Discontinuation of Therapy : The available data suggest that the dosage of cilostazol can be reduced or discontinued without rebound (i.e., platelet hyperaggregability).

Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared to placebo in patients with class III-IV congestive heart failure. Cilostazol tablets are contraindicated in patients with congestive heart failure of any severity. Cilostazol tablets are contraindicated in patients with haemostatic disorders or active pathologic bleeding, such as bleeding peptic ulcer and intracranial bleeding. Cilostazol tablets inhibit platelet aggregation in a reversible manner. Cilostazol tablets are contraindicated in patients with known or suspected hypersensitivity to any of its components.

Hematologic adverse reactions: Rare cases have been reported of thrombocytopenia or leucopenia progressing to agranulocytosis when cilostazol was not immediately discontinued. The agranulocytosis, however, was reversible on discontinuation of Cilostazol.

Drug Interactions : Since cilostazol is extensively metabolized by cytochrome P-450 isoenzymes, caution should be exercised when cilostazol is coadministered with inhibitors of CYP3A4 such as ketoconazole and erythromycin or inhibitors of CYP2C19 such as omeprazole. Pharmacokinetic studies have demonstrated that omeprazole and erythromycin significantly increased the systemic exposure of cilostazol and/or its major metabolites. Population pharmacokinetic studies showed higher concentrations of cilostazol among patients concurrently treated with diltiazem, an inhibitor of CYP3A4 (see CLINICAL PHARMACOLOGY, Pharmacokinetic and Pharmacodynamic Drug-Drug Interactions ). Cilostazol does not, however, appear to cause increased blood levels of drugs metabolized by CYP3A4, as it had no effect on lovastatin, a drug with metabolism very sensitive to CYP3A4 inhibition.

HOW SUPPLIED Cilostazol tablets 50 mg are white, round compressed tablets debossed “cor” over “158” on one side and other side is plain. They are supplied as follows: NDC 64720-158-06   in bottles of 60's NDC 64720-158-10   in bottles of 100's NDC 64720-158-50   in bottles of 500's NDC 64720-158-11   in bottles of 1000's Cilostazol tablets 100mg are white,round compressed tablets debossed "cor" over "159" on one side and other side is plain. They are supplied as follows: NDC 64720-159-06   in bottles of 60's NDC 64720-159-10   in bottles of 100's NDC 64720-159-50   in bottles of 500's NDC 64720-159-11   in bottles of 1000's STORAGE Store at 20 to 25°C (68 to 77°F) excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight container as defined in the USP/NF. Keep this and all drugs out of the reach of children. Rev. July 2009 MF # 334-03 Manufactured and Distributed by: Corepharma LLC Middlesex, NJ 08846

Mechanism of Action: The mechanism of the effects of cilostazol on the symptoms of intermittent claudication is not fully understood. Cilostazol and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelet and blood vessels, leading to inhibition of platelet aggregation and vasodilation, respectively. Cilostazol reversibly inhibits platelet aggregation induced by a variety of stimuli, including thrombin, ADP, collagen, arachidonic acid, epinephrine, and shear stress. Effects on circulating plasma lipids have been examined in patients taking cilostazol. After 12 weeks, as compared to placebo, cilostazol 100 mg b.i.d. produced a reduction in triglycerides of 29.3 mg/dL (15%) and an increase in HDL-cholesterol of 4.0 mg/dL ( ≅10%). Cardiovascular Effects: Cilostazol affects both vascular beds and cardiovascular function. It produces non-homogeneous dilation of vascular beds, with greater dilation in femoral beds than in vertebral, carotid, or superior mesenteric arteries. Renal arteries were not responsive to the effects of cilostazol. In dogs or cynomolgous monkeys, cilostazol increased heart rate, myocardial contractile force, and coronary blood flow as well as ventricular automaticity, as would be expected for a PDE III inhibitor. Left ventricular contractility was increased at doses required to inhibit platelet aggregation. A-V conduction was accelerated. In humans, heart rate increased in a dose-proportional manner by a mean of 5.1 and 7.4 beats per minute in patients treated with 50 and 100 mg b.i.d., respectively. In 264 patients evaluated with Holter monitors, numerically more cilostazol-treated patients had increases in ventricular premature beats and non-sustained ventricular tachycardia events than did placebo-treated patients; the increases were not dose-related.

CILOSTAZOL 100MG LABEL IMAGE CILOSTAZOL 100MG LABEL IMAGE