cilostazol (Pletal)

Dosing and uses of Pletal (cilostazol)

• Adult
• Pediatric

 

Adult dosage forms and strengths

tablet

• 50mg
• 100mg

 

Peripheral Vascular Disease

100 mg PO q12hr 30 minutes before or 2 hours after meals

Dosing considerations

• CYP2C19 or CYP3A4 inhibitors: Reduce dosage to 50 mg PO q12hr

 

Thrombotic Complications of Coronary Angioplasty (Off-label)

100 mg q12hr 30 minutes before or 2 hours after meals

Dosing considerations

• May be administered alone or in combination with aspirin 81 mg/day

 

Renal Impairment

CrCl< 25 mL/min: Use caution

 

Hepatic Impairment

Moderate to severe: Use caution

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Pletal (cilostazol) adverse (side) effects

>10%

Headache (27-34%)

Diarrhea (12-19%)

Abnormal stools (12-15%)

Infection (10-14%)

Rhinitis (7-12%)

Pharyngitis (7-10%)

 

1-10%

Dizziness (9-10%)

Palpitations (5-10%)

Peripheral edema (7-9%)

Back pain (6-7%)

Dyspepsia (6%)

Abdominal pain (4-5%)

Tachycardia (4%)

Increased cough (3-4%)

Myalgia (2-3%)

Atrial fibrillation (<2%)

CHF (<2%)

MI (<2%)

Hematemesis (<2%)

Ecchymosis (<2%)

Blood in eye (<2%)

Epistaxis (<2%)

Hemoptysis (<2%)

Nausea

 

Frequency not defined

Decreased platelet aggregation

Agranulocytosis

Aplastic anemia

Leukopenia

Thrombocytopenia

Stevens-Johnson syndrome

 

Postmarketing Reports

Blood and lymphatic system disorders: Agranulocytosis, aplastic anemia, granulocytopenia, thrombocytopenia, leukopenia, bleeding tendency

Cardiovascular: Torsades de pointes, QTc prolongation

GI: GI hemorrhage

General: Pain, chest pain, hot flushes, extradural or subdural hematoma, hyperglycemia, hyperuricemia, increased BUN, elevated BP, decreased platelet or white blood cell (WBC) count

Hepatic: Hepatic dysfunction, abnormal liver function tests, jaundice

Neurologic: Intracranial or cerebral hemorrhage, cerebrovascular accident (CVA)

Respiratory: Pulmonary hemorrhage, interstitial pneumonia

Skin: Subcutaneous hemorrhage, pruritus, skin eruptions such as Stevens-Johnson syndrome, skin drug eruption (dermatitis medicamentosa)

Vascular: Subacute thrombosis

 

Warnings

Black box warnings

Cilostazol and metabolites are inhibitors of phosphodiesterase III; such activity has been shown to decrease survival of patients with class III-IV CHF; contraindicated in patients with CHF of any severity

 

Contraindications

Congestive heart failure of any severity

Hypersensitivity

Hemostatic disorders or active pathologic bleeding (eg, bleeding peptic ulcer, intracranial bleeding) due to reversible platelet aggregation

 

Cautions

Use with caution in liver and renal disease

Leukopenia that progresses to agranulocytosis may occur (in which case, discontinue therapy)

Discontinue therapy if thrombocytopenia occurs

Use with caution in patients taking platelet aggregation inhibitors

Do not administer for at least 4-6 half-lives before elective surgical procedures

Avoid grapefruit juice

Response may be seen as early as 2-4 weeks after initiation, but treatment may be needed for up to 12 weeks

Dosage can be reduced or discontinued without rebound effects (eg, platelet hyperaggregability)

Cilostazol may induce tachycardia, palpitation, tachyarrhythmia and/or hypotension; patients with history of ischemic heart disease may be at risk for exacerbations of angina pectoris or myocardial infarction

Plasma concentrations and overall pharmacological activity are increased when cilostazol is administered with strong or moderate CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, diltiazem) and strong CYP2C19 inhibitors (eg, ticlopidine, fluconazole, omeprazole); dose reduction to 50 mg twice daily should be considered

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Excretion in milk unknown; not recommended

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Pletal (cilostazol)

Mechanism of action

Inhibits phosphodiesterase III, causing cyclic adenosine monophosphate (cAMP) to increase, which in turn inhibits platelet aggregation; causes homogeneous vasodilation, especially in femoral vascular beds

 

Absorption

Onset: 2-12 weeks

 

Distribution

Protein bound: 95-98% (especially albumin)

 

Metabolism

Metabolized by CYP3A4 (major), CYP2C19

Metabolites: 4'-trans-hydroxy-cilostazol, 3,4-dehydro-cilostazoL

 

Elimination

Half-life: 11-13 hr

Dialyzable: No

Excretion: Urine (74%), feces (20%)