Skip to Content

Cilostazol

Class: Platelet-aggregation Inhibitors
Chemical Name: 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1H)-quinolinone
Molecular Formula: C20H27N5O2
CAS Number: 73963-72-1
Brands: Pletal

Medically reviewed by Drugs.com. Last updated on Feb 5, 2021.

Warning

  • Contraindicated in patients with CHF of any severity. Decreased survival observed in patients with NYHA class III or IV CHF who received other drugs that inhibit phosphodiesterase (PDE) type 3.

Introduction

Platelet-aggregation inhibitor and arterial vasodilator.

Uses for Cilostazol

Intermittent Claudication

Symptomatic management of intermittent claudication (improvement in walking distance and speed).

The American College of Chest Physicians (ACCP) suggests addition of cilostazol to aspirin or clopidogrel therapy in patients with refractory intermittent claudication who do not respond to conservative measures (e.g., smoking cessation, exercise).

Improves walking distance and speed in patients with stable intermittent claudication.

Efficacy not established in patients with rapidly progressing claudication, leg pain at rest, ischemic leg ulcers, or gangrene.

Long-term effects on limb preservation and hospitalization not fully elucidated.

Thrombotic Complications of Coronary Angioplasty

Has been used alone or in combination with other antiplatelet agents (e.g., aspirin, clopidogrel) to prevent thrombosis and restenosis following coronary angioplasty/stenting. However, use of cilostazol in patients with coronary artery stents generally not recommended by experts, except possibly in those with allergy or intolerance to aspirin or clopidogrel; in such cases, ACCP suggests possible use as a substitute for either aspirin or clopidogrel in a dual antiplatelet regimen.

Ischemic Stroke

Has been used for secondary prevention of noncardioembolic stroke or TIAs in patients with a history of TIAs or ischemic stroke.

ACCP, the American Stroke Association (ASA), and AHA consider cilostazol an acceptable antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke or TIAs; other options include aspirin monotherapy, clopidogrel, or the combination of aspirin and extended-release dipyridamole. When selecting an appropriate antiplatelet regimen, consider factors such as the patient's individual risk for recurrent stroke, tolerance, and cost of the different agents.

Cilostazol Dosage and Administration

Administration

Oral Administration

Administer orally at least one-half hour before or 2 hours after breakfast and dinner.

Dosage

Adults

Intermittent Claudication
Oral

100 mg twice daily.

Patients receiving concomitant therapy with CYP3A4 (e.g., diltiazem, erythromycin, itraconazole, ketoconazole) or CYP2C19 (e.g., omeprazole) inhibitors: Initially, 50 mg twice daily. (See Specific Drugs and Foods under Interactions.)

Thrombotic Complications of Coronary Angioplasty†
Oral

100 mg twice daily has been used as a substitute for either aspirin or clopidogrel as part of a dual antiplatelet regimen in patients with coronary artery stents who have an allergy or intolerance to aspirin or clopidogrel.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time. (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations at this time. (See Renal Impairment under Cautions.)

Cautions for Cilostazol

Contraindications

  • CHF of any severity. (See Boxed Warning.)

  • Hemostatic disorders or active pathologic bleeding, such as bleeding peptic ulcer or intracranial bleeding.

  • Known hypersensitivity to cilostazol or any ingredient in the formulation.

Warnings/Precautions

General Precautions

Cardiovascular Effects

Consider possible adverse cardiovascular effects (e.g., increased heart rate) when used in patients with heart disease (e.g., CAD). Long-term effects not known in patients with underlying heart disease more severe than that studied in clinical trials (i.e., no recent MI or stroke, no arrhythmias, no unstable angina or other signs of rapidly progressing cardiovascular disease). Do not use in patients with CHF. (See Boxed Warning.)

Use with Clopidogrel

Limited information regarding safety and efficacy of concurrent use with clopidogrel. Unknown whether concurrent clopidogrel therapy has additive effect on bleeding time. Use caution and monitor bleeding times during concomitant therapy.

Hematologic Effects

Possible thrombocytopenia or leukopenia progressing to agranulocytosis if cilostazol is not immediately discontinued; agranulocytosis reversible with discontinuance of cilostazol.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats; discontinue nursing or drug because of potential risk in nursing infants.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Not studied in patients with moderate to severe hepatic impairment; use with caution.

Renal Impairment

Use with particular caution in patients with severe renal impairment (Clcr <25 mL/minute). Safety and efficacy not established in patients undergoing hemodialysis. (See Elimination Route under Pharmacokinetics.)

Common Adverse Effects

Headache, diarrhea, abnormal (e.g., loose) stools, dizziness, infection, palpitation, pharyngitis, back pain, nausea, peripheral edema, rhinitis, dyspepsia, increased cough, tachycardia.

Interactions for Cilostazol

Metabolized by CYP3A4, and to a lesser extent, CYP2C19.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4 and CYP2C19: potential pharmacokinetic interaction (increased plasma cilostazol concentrations, decreased clearance).

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Antifungals, azoles

Possible increased plasma cilostazol concentrations

If used concomitantly, consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Anti-infectives, macrolides

Possible increases in plasma cilostazol concentrations with certain macrolide antibiotics (e.g., erythromycin, clarithromycin)

Pharmacokinetic interaction unlikely with azithromycin

If used concomitantly with certain macrolide antibiotics (e.g., erythromycin, clarithromycin), consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Aspirin

Potential additive effects on aPTT, PT, and/or bleeding time

Increased risk of hemorrhage not observed with low-dose aspirin; effect of concurrent analgesic doses of aspirin not known

Clopidogrel

Potential additive antiplatelet effects

Pharmacokinetic interaction unlikely

Caution advised; monitor bleeding times during concurrent administration

Danazol

Possible increases in plasma cilostazol concentrations

If used concomitantly, consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Diltiazem

Increased plasma cilostazol concentrations and decreased clearance

If used concomitantly, consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Fluoxetine

Possible increases in plasma cilostazol concentrations

If used concomitantly, consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Fluvoxamine

Possible increases in plasma cilostazol concentrations

If used concomitantly, consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Grapefruit juice

Peak plasma cilostazol concentrations increased by about 50% but no effect on AUC

Indinavir

Possible increased plasma cilostazol concentrations

Lovastatin

Possible pharmacokinetic interaction; increased plasma lovastatin concentration and decreased plasma cilostazol concentration

Not considered clinically important

Nefazodone

Possible increased plasma cilostazol concentrations

If used concomitantly, consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Omeprazole

Increased plasma concentrations of active cilostazol metabolite (3,4-dehydro-cilostazol)

Use with caution; if used concomitantly, consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Quinidine

Pharmacokinetic interaction unlikely

Sertraline

Possible increases in plasma cilostazol concentrations

If used concomitantly, consider reduced cilostazol dosage (i.e., 50 mg twice daily)

Warfarin

Potential additive effects on aPTT, PT, and/or platelet aggregation

Pharmacokinetic and pharmacodynamic effects of multiple-dose concurrent therapy not known

Cilostazol Pharmacokinetics

Absorption

Bioavailability

Absorbed following oral administration; bioavailability not determined.

Onset

Peak pharmacodynamic effects (antiplatelet activity, heart-rate increase, decrease in DBP) within approximately 6 hours. In intermittent claudication, symptomatic relief may occur within 2–4 weeks of initial therapy; ≤12 weeks may be required to obtain optimum therapeutic effect.

Food

Food increases absorption; approximately 90% increase in peak plasma concentration and 25% increase in AUC when administered with a high-fat meal.

Increased plasma concentrations may be associated with a higher incidence of adverse effects; drug should be taken on an empty stomach. (See Oral Administration under Dosage and Administration.)

Concomitant ingestion of grapefruit juice increased peak plasma cilostazol concentrations by approximately 50% but had no effect on AUC.

Distribution

Extent

Distributed into milk in rats; not known whether crosses placenta or distributes into milk in humans.

Plasma Protein Binding

95–98% (mainly albumin).

Special Populations

In patients with severe renal impairment, metabolite levels increase, and protein binding of drug and metabolites altered; overall drug activity appears unchanged.

In patients who smoke, drug exposure decreases by approximately 20%.

Elimination

Metabolism

Metabolized to active metabolites in the liver by CYP isoenzymes, principally CYP3A4, and to lesser extent, by CYP2C19. Two metabolites are active; one metabolite accounts for ≥50% of pharmacologic activity (PDE inhibition).

Elimination Route

Excreted principally in urine (74%) and also in feces (20%) as active and inactive metabolites.

Unlikely to be removed by hemodialysis because of high (95–98%) protein binding.

Half-life

Approximately 11–13 hours (drug and active metabolites).

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).

Actions

  • Quinolinone-derivative selective phosphodiesterase (PDE) type 3 inhibitor; platelet-aggregation inhibitor and arterial vasodilator.

  • Appears to inhibit activation of cellular PDE type 3, resulting in suppressed degradation and increased concentrations of cyclic adenosine-3′,5′-monophosphate (cAMP) in platelets and blood vessels. Increased cAMP concentrations appear to mediate arterial vasodilation and inhibition of platelet aggregation.

  • Favorably alters concentrations of certain lipoproteins; reduces plasma triglycerides and increases HDL-cholesterol concentrations. No effect on plasma concentrations of total cholesterol, LDL-cholesterol, or lipoprotein(a) (Lp[a]).

Advice to Patients

  • Importance of providing patient a copy of manufacturer’s patient information each time therapy is prescribed.

  • Importance of adherence to prescribed directions for use.

  • Importance of not taking cilostazol if CHF (e.g., shortness of breath, swelling of the legs) is present.

  • Importance of taking cilostazol at least one-half hour before or 2 hours after food.

  • Importance of informing patient that up to 12 weeks of cilostazol therapy may be required before symptomatic relief of intermittent claudication occurs.

  • Importance of informing patient that cardiovascular risk during long-term use or in patients with severe underlying heart disease currently is not known.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cilostazol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

50 mg*

Pletal

Otsuka

100 mg*

Pletal

Otsuka

AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Show article references