Overview
11 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 369.47. Cilostazol is 6-[4-(1-cyclohexyl-1 H -tetrazol-5-yl) butoxy]-3,4-dihydro-2(1 H )-quinolinone, CAS-73963-72-1.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Cilostazol and several of its metabolites inhibit phosphodiesterase III activity and suppress cAMP degradation with a resultant increase in cAMP in platelets 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. Cardiovascular effects: Cilostazol affects both vascular beds and cardiovascular function. It produces heterogeneous 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.
Indications
- 1 INDICATIONS AND USAGE Cilostazol tablets are indicated for the reduction of symptoms of intermittent claudication, as demonstrated by an increased walking distance. Cilostazol is a phosphodiesterase III inhibitor (PDE III inhibitor) indicated for the reduction of symptoms of intermittent claudication, as demonstrated by an increased walking distance ( 1 )
Common Doses
- 100 mg
- 50 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of cilostazol is 100 mg twice daily taken at least half an hour before or two hours after breakfast and dinner ( 2.1 ) Reduce the dose to 50 mg twice daily when coadministered with CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin, and diltiazem, or CYP2C19 inhibitors such as ticlopidine, fluconazole, and omeprazole ( 2.2 ) 2.1 Recommended dosage The recommended dosage of cilostazol is 100 mg twice daily taken at least half an hour before or two hours after breakfast and dinner.
Black Box Warning
WARNING: CONTRAINDICATED IN HEART FAILURE PATIENTS Cilostazol tablets are contraindicated in patients with heart failure of any severity. 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 heart failure [see Contraindications ( 4 )] . WARNING: CONTRAINDICATED IN HEART FAILURE PATIENTS See full prescribing information for complete boxed warning. Cilostazol tablets is contraindicated in patients with heart failure of any severity.
Contraindications
- 4 CONTRAINDICATIONS Cilostazol is contraindicated in patients with: Heart failure of any severity: 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 heart failure. Hypersensitivity to cilostazol or any components of cilostazol tablets (e.g., anaphylaxis, angioedema) Heart failure of any severity ( 4 ) Hypersensitivity to cilostazol or any components of cilostazol tablets ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Patients with Heart Failure [see Boxed Warning] Tachycardia [see Warnings and Precautions ( 5.1 )] Left Ventricular Outflow Tract Obstruction [see Warnings and Precautions ( 5.2 )] Hematologic Adverse Reactions [see Warnings and Precautions ( 5.3 )] Hemostatic Disorders or Active Pathologic Bleeding [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Strong and moderate CYP3A4 and CYP2C19 inhibitors: Increase exposure to cilostazol. Reduce cilostazol tablets dose ( 2.2 , 7.1 ) 7.1 Inhibitors of CYP3A4 or CYP2C19 Inhibitors of CYP3A4 Coadministration of strong (e.g., ketoconazole) and moderate (e.g., erythromycin, diltiazem and grapefruit juice) CYP3A4 inhibitors can increase exposure to cilostazol. Reduce cilostazol dose to 50 mg twice daily when coadministered with strong or moderate inhibitors of CYP3A4 [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )].