Phosphodiesterase Enzyme Inhibitor; Platelet Aggregation Inhibitor

Symptomatic management of peripheral vascular disease, primarily intermittent claudication; currently being investigated for the treatment of acute coronary syndromes

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In animal studies, abnormalities of the skeletal, renal and cardiovascular system were increased. In addition, the incidence of stillbirth and decreased birth weights were increased. It is not known whether cilostazol is excreted in human milk. Because of the potential risk to nursing infants, a decision to discontinue the drug or discontinue nursing should be made.

Hypersensitivity to cilostazol or any component of the formulation; heart failure (of any severity)

Use with caution in patients receiving platelet aggregation inhibitors (effects are unknown), hepatic impairment (not studied). Use with caution in patients receiving inhibitors of CYP3A4 (such as ketoconazole or erythromycin) or inhibitors of CYP2C19 (such as omeprazole); use with caution in severe underlying heart disease; use is not recommended in nursing mothers

>10%:

Central nervous system: Headache (27% to 34%)

Gastrointestinal: Abnormal stools (12% to 15%), diarrhea (12% to 19%)

Miscellaneous: Infection (10% to 14%)

2% to 10%:

Cardiovascular: Peripheral edema (7% to 9%), palpitation (5% to 10%), tachycardia (4%)

Central nervous system: Dizziness (9% to 10%)

Gastrointestinal: Dyspepsia (6%), nausea (6% to 7%), abdominal pain (4% to 5%), flatulence (2% to 3%)

Neuromuscular & skeletal: Back pain (6% to 7%), myalgia (2% to 3%)

Respiratory: Rhinitis (7% to 12%), pharyngitis (7% to 10%), cough (3% to 4%)

<2%: Chills, facial edema, fever, edema, malaise, nuchal rigidity, pelvic pain, retroperitoneal hemorrhage, cerebral infarction/ischemia, congestive heart failure, cardiac arrest, hemorrhage, hypotension, myocardial infarction/ischemia, postural hypotension, ventricular arrhythmia, supraventricular arrhythmia, syncope, anorexia, cholelithiasis, colitis, duodenitis, peptic ulcer, duodenal ulcer, esophagitis, esophageal hemorrhage, gastritis, hematemesis, melena, tongue edema, diabetes mellitus, anemia, ecchymosis, polycythemia, purpura, increased creatinine, gout, hyperlipidemia, hyperuricemia, arthralgia, bone pain, bursitis, anxiety, insomnia, neuralgia, dry skin, urticaria, amblyopia, blindness, conjunctivitis, diplopia, retinal hemorrhage, cystitis, albuminuria, vaginitis, vaginal hemorrhage, urinary frequency

Experience with overdosage in humans is limited. Headache, diarrhea, hypotension, tachycardia and/or cardiac arrhythmias may occur. Treatment is symptomatic and supportive. Hemodialysis is unlikely to be of value. In some animal models, high-dose or long-term administration was associated with a variety of cardiovascular lesions, including endocardial hemorrhage, hemosiderin deposition and left ventricular fibrosis, coronary arteritis, and periarteritis.

CYP3A4 and CYP2C19 cytochrome enzyme substrate

Cilostazol and its metabolites are inhibitors of phosphodiesterase III. As a result cyclic AMP is increased leading to inhibition of platelet aggregation and vasodilation. Other effects of phosphodiesterase III inhibition include increased cardiac contractility, accelerated AV nodal conduction, increased ventricular automaticity, heart rate, and coronary blood flow.

Onset: 2-4 weeks; treatment for up to 12 weeks may be required before benefit is experienced

Protein binding: 97% to 98%

Metabolism: Hepatic, via CYP3A4 and CYP2C19; at least one metabolite has significant activity

Half-life: 11-13 hours

Elimination: In urine (74%) and feces (20%), as metabolites

Adults: Oral: 100 mg twice daily taken at least one-half hour before or 2 hours after breakfast and dinner; dosage should be reduced to 50 mg twice daily during concurrent therapy with inhibitors of CYP3A4 or CYP2C19 (see Drug Interactions)

Avoid concurrent ingestion of grapefruit juice due to the potential to inhibit CYP3A4. Avoid administration with meals. Taking cilostazol with a high-fat meal increases the AUC by 25% and the peak concentration may be increased by 90%; it is best to take cilostazol 30 minutes before or 2 hours after meals.

Dizziness is common; may cause anxiety or insomnia

CYP3A4 inhibitors (fluvoxamine, fluoxetine, nefazodone, sertraline) may increase the concentrations of cilostazol

No information available to require special precautions

Tongue edema has been observed (according to manufacturer); if a patient is to undergo elective surgery and an antiplatelet effect is not desired, a medical consult is suggested to consider reduction or discontinuation of cilostazol dose prior to surgery

Use exactly as directed; do not discontinue without consulting prescriber. Beneficial effect may take between 2-12 weeks. Take on empty stomach (30 minutes before or 2 hours after meals). Do not take with grapefruit juice. You may experience nervousness, dizziness, or fatigue (use caution when driving or engaging in tasks requiring alertness until response to treatment is known); nausea, vomiting, or flatulence (frequent small meals, frequent mouth care, chewing gum or sucking hard candy may help); or postural hypotension (change position slowly when rising from sitting or lying position or climbing stairs). Report chest pain, palpitations, unusual heart beat, or swelling of extremities; unusual bleeding; unresolved GI upset or pain; dizziness, nervousness, sleeplessness, or fatigue; muscle cramping or tremor; unusual cough; or other adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Tablet: 50 mg, 100 mg