Class: Aggregation inhibitor
- Tablets 50 mg
- Tablets 100 mg
Inhibits cellular phosphodiesterase and exhibits a higher specificity for phosphodiesterase III.
A high-fat meal increases C max approximately 90% and AUC 25%.
95% to 98% protein bound, predominantly to albumin.
Extensively metabolized in the liver by CYP3A4 and, to a lesser extent, CYP2C19. Two of the metabolites are active.
The t ½ is approximately 11 to 13 h. Approximately 74% is excreted in the urine and 20% in the feces as metabolites.
Special PopulationsRenal Function Impairment
Severe renal function impairment increases metabolic levels and alters protein binding of the parent and metabolites.Hepatic Function Impairment
Patients with moderate or severe hepatic function impairment have not been studied.Smoking
Smoking decreased exposure approximately 20%.
Indications and Usage
Reduction of symptoms of intermittent claudication as indicated by an increased walking distance.
CHF of any severity; hypersensitivity to any components of the product; patients with hemostatic disorders or active pathologic bleeding (eg, bleeding ulcer, intracranial bleeding).
Dosage and AdministrationIntermittent Claudication
PO 100 mg twice daily, taken at least 30 min before or 2 h after breakfast and dinner. Consider a dosage reduction to 50 mg twice daily during coadministration of CYP2C19 inhibitors such as omeprazole or CYP3A4 inhibitors such as diltiazem, erythromycin, itraconazole, and ketoconazole.
Store at 59° to 86°F.
Short-term (up to 4 days) coadministration of aspirin with cilostazol showed a 22% to 37% increase in inhibition of adenosine diphosphate–induced ex vivo platelet aggregation compared with aspirin alone.Moderate inhibitors of CYP3A4 (eg, clarithromycin, diltiazem, erythromycin, grapefruit juice)
Cilostazol plasma concentrations may be elevated, increasing the pharmacologic and adverse reactions.Omeprazole
Coadministration of omeprazole did not significantly affect the metabolism of cilostazol, but the systemic exposure to 3,4-dehydro-cilostazol was increased 69%.CYP-450 system
Cilostazol could have pharmacokinetic interactions because of effects of other drugs on its metabolism by CYP3A4 or CYP2C19.Platelet function inhibitors
Cilostazol could have pharmacodynamic interactions with other platelet function inhibitors.Strong inhibitors of CYP3A4 (eg, fluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone)
Cilostazol plasma concentrations may be elevated, increasing the pharmacologic and adverse reactions.
Laboratory Test Interactions
None well documented.
Palpitation (10%); tachycardia (4%); atrial fibrillation, atrial flutter, cerebral infarct, cerebral ischemia, CHF, heart arrest, hemorrhage, hypotension, MI, myocardial ischemia, nodal arrhythmia, postural hypotension, supraventricular tachycardia, syncope, varicose vein, vasodilation, ventricular extrasystoles, ventricular tachycardia (less than 2%); QTc prolongation, subacute thrombosis, torsades de pointes (postmarketing).
Headache (34%); dizziness (10%); vertigo (3%); anxiety, insomnia, malaise, neuralgia (less than 2%); cerebral hemorrhage, cerebrovascular accident, intracranial hemorrhage (postmarketing).
Dry skin, furunculosis, skin hypertrophy, urticaria (less than 2%); pruritus, skin drug eruption (dermatitis medicamentosa), skin eruptions including Stevens-Johnson syndrome, subcutaneous hemorrhage (postmarketing).
Rhinitis (12%); pharyngitis (10%); amblyopia, blindness, conjunctivitis, diplopia, ear pain, eye hemorrhage, retinal hemorrhage, tinnitus (less than 2%).
Diabetes mellitus (less than 2%).
Diarrhea (19%); abnormal stools (15%); nausea (7%); dyspepsia (6%); abdominal pain (5%); flatulence (3%); anorexia, colitis, duodenal ulcer, duodenitis, esophageal hemorrhage, esophagitis, gastritis, gastroenteritis, gum hemorrhage, hematemesis, increased gamma-glutamyltransferase, melena, peptic ulcer, periodontal abscess, rectal hemorrhage, stomach ulcer, tongue edema (less than 2%); GI hemorrhage (postmarketing).
Albuminuria, cystitis, urinary frequency, vaginal hemorrhage, vaginitis (less than 2%).
Anemia, ecchymosis, iron deficiency anemia, polycythemia, purpura (less than 2%); agranulocytosis, bleeding tendency, granulocytopenia, leukopenia, thrombocytopenia (postmarketing).
Cholelithiasis (less than 2%); hepatic function impairment/abnormal LFTs, jaundice (postmarketing).
Decreased platelet count, decreased WBC, increased blood glucose, increased blood uric acid, increased BUN (postmarketing).
Peripheral edema (9%); gout, hyperlipemia, hyperuricemia, increased creatinine, (less than 2%).
Back pain (7%); myalgia (3%); arthralgia, bone pain, bursitis, neck rigidity, pelvic pain (less than 2%).
Increased cough (4%); asthma, epistaxis, hemoptysis, pneumonia, sinusitis (less than 2%); interstitial pneumonia, pulmonary hemorrhage (postmarketing).
Infection (14%); chills, face edema, fever, generalized edema, retroperitoneal hemorrhage (less than 2%); chest pain, extradural hematoma, hot flushes, pain, subdural hematoma (postmarketing).
Contraindicated for use in CHF patients of any severity. Cilostazol and metabolites are inhibitors of phosphodiesterase III. Such activity has been shown to decrease survival of patients with class III to IV CHF.
Monitor patient for signs and symptoms of bleeding, especially those concurrently on other anticoagulants. Assess patient for adverse cardiac signs and symptoms and for signs of CHF.
Category C .
Safety and efficacy in children have not been established.
Use with caution in patients with severe renal function impairment (Ccr less than 25 mL/min).
Use with caution.
Thrombocytopenia or leukopenia progressing to agranulocytosis has been reported; however, agranulocytosis was reversible on immediate discontinuation of cilostazol.
Cardiac arrhythmias, diarrhea, hypotension, severe headache, tachycardia.
- Instruct patient to take cilostazol as directed and to read the patient package insert before starting therapy or restarting therapy.
- Advise patient to inform health care provider if taking or planning to take any OTC medications because there is a potential for drug interactions.
- Advise patient that beneficial effects of cilostazol may not be immediate; relief of symptoms may require 2 to 12 wk.
- Instruct patient to avoid consuming grapefruit juice to avoid drug/food interactions.
- Advise smokers of risks, including potential interaction with the drug, and the benefits of not smoking.
- Warn patient, especially patient with underlying heart disease, of the uncertainty concerning the CV risk with long-term use. Instruct patient to report adverse cardiac symptoms immediately to health care provider before taking next dose.
- Advise patient not to take aspirin or an NSAID without informing health care provider.
- Instruct patient to inform primary caregiver of any adverse reactions.
- Warn women of childbearing potential to avoid becoming pregnant and apprise them of the potential hazard to the fetus.
- Warn breast-feeding mothers of the danger of transferring the drug to the baby through mother's milk and possible infant effects. Patients decide to discontinue the drug or breast-feeding in collaboration with health care provider.
- Instruct patient to report any unusual reaction or concern to health care provider.
Copyright © 2009 Wolters Kluwer Health.
More about cilostazol
- Other brands: Pletal