Cilostazol is contraindicated with 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 with placebo in patients with class III to IV heart failure.
Intermittent claudication:
Note: Safe to use in combination with either aspirin or clopidogrel (Ref).
Oral: 100 mg twice daily; discontinue treatment if symptoms are not improved after 3 months of therapy.
Noncardioembolic stroke or transient ischemic attack, secondary prevention (off-label use): Oral: 100 mg twice daily. Note: Clopidogrel or aspirin/extended release dipyridamole recommended over the use of cilostazol (Ref).
Percutaneous coronary intervention (following elective stent placement) (off-label use): Oral: 100 mg twice daily in combination with aspirin or clopidogrel. Note: Only recommended in patients with an allergy or intolerance to either aspirin or clopidogrel (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Oral:
CrCl >25 mL/minute: No dosage adjustment necessary (Ref).
CrCl ≤25 mL/minute: No dosage adjustment necessary. Use with caution as patients with severe kidney impairment have increased concentrations of an active metabolite (OPC-13213) (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal SCr concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Oral: No data. No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly removed by dialysis (highly protein bound [95% to 98%]) (Ref):
Oral: No dosage adjustment necessary (Ref). A retrospective trial has reported tolerability with use of 100 mg twice daily in hemodialysis patients (Ref). Use with caution as patients with severe kidney impairment have increased concentrations of an active metabolite (OPC-13213) (Ref).
Peritoneal dialysis: Unlikely to be significantly removed by dialysis (highly protein bound [95% to 98%]) (Ref):
Oral: No dosage adjustment necessary (Ref). Use with caution as patients with severe kidney impairment have increased concentrations of an active metabolite (OPC-13213) (Ref).
CRRT: Oral: No dosage adjustment necessary (Ref). Use with caution as patients with severe kidney impairment have increased concentrations of an active metabolite (OPC-13213) (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral: No dosage adjustment necessary (Ref). Use with caution as patients with severe kidney impairment have increased concentrations of an active metabolite (OPC-13213) (Ref).
Mild impairment: No dosage adjustment necessary.
Moderate to severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (27% to 34%)
Gastrointestinal: Diarrhea (12% to 19%), abnormal stools (12% to 15%)
Infection: Infection (10% to 14%)
Respiratory: Rhinitis (7% to 12%)
1% to 10%:
Cardiovascular: Palpitations (5% to 10%), peripheral edema (7% to 9%), tachycardia (4%), atrial fibrillation (<2%), atrial flutter (<2%), cardiac arrest (<2%), cardiac failure (<2%), cerebral infarction (<2%), edema (<2%), facial edema (<2%), hypotension (<2%), myocardial infarction (<2%), nodal arrhythmia (<2%), orthostatic hypotension (<2%), supraventricular tachycardia (<2%), syncope (<2%), varicose veins (<2%), ventricular premature contractions (<2%), ventricular tachycardia (<2%)
Central nervous system: Dizziness (9% to 10%), vertigo (3%) , anxiety (<2%), chills (<2%), insomnia (<2%), malaise (<2%), neuralgia (<2%)
Dermatologic: Ecchymoses (<2%), furunculosis (eye: <2%), skin hypertrophy (<2%), urticaria (<2%), xeroderma (<2%)
Endocrine & metabolic: Albuminuria (<2%), diabetes mellitus (<2%), gout (<2%), hyperlipidemia (<2%), hyperuricemia (<2%), increased gamma-glutamyl transferase (<2%)
Gastrointestinal: Nausea (7%), dyspepsia (6%), abdominal pain (4% to 5%), flatulence (3%), anorexia (<2%), cholelithiasis (<2%), colitis (<2%), duodenal ulcer (<2%), duodenitis (<2%), esophageal hemorrhage (<2%), esophagitis (<2%), gastric ulcer (<2%), gastritis (<2%), gastroenteritis (<2%), gingival hemorrhage (<2%), hematemesis (<2%), melena (<2%), peptic ulcer (<2%), periodontal abscess (<2%)
Genitourinary: Cystitis (<2%), pelvic pain (<2%), urinary frequency (<2%), vaginal hemorrhage (<2%), vaginitis (<2%)
Hematologic & oncologic: Anemia (<2%), hemorrhage (<2%), hemorrhage (eye, <2%), iron deficiency anemia (<2%), polycythemia (<2%), purpura (<2%), rectal hemorrhage (<2%), retroperitoneal hemorrhage (<2%)
Hypersensitivity: Tongue edema (<2%)
Neuromuscular & skeletal: Back pain (7%), myalgia (3%), arthralgia (<2%), bursitis (<2%), neck stiffness (<2%), ostealgia (<2%)
Ophthalmic: Amblyopia (<2%), blindness (<2%), conjunctivitis (<2%), diplopia (<2%), retinal hemorrhage (<2%)
Otic: Otalgia (<2%), tinnitus (<2%)
Renal: Increased serum creatinine (<2%)
Respiratory: Pharyngitis (10%), cough (3% to 4%), asthma (<2%), epistaxis (<2%), hemoptysis (<2%), pneumonia (<2%), sinusitis (<2%)
Miscellaneous: Fever (<2%)
Postmarketing and/or case reports: Abnormal hepatic function tests, agranulocytosis, anaphylaxis, angina pectoris, angioedema, aplastic anemia, cerebrovascular accident, cerebral hemorrhage, chest pain, coronary thrombosis (stent), fixed drug eruption, gastrointestinal hemorrhage, granulocytopenia, hematoma (extradural), hematuria, hemorrhagic diathesis, hepatic insufficiency, hot flash, hyperglycemia, hypersensitivity, hypertension, increased blood pressure, increased blood urea nitrogen, interstitial pneumonitis, intracranial hemorrhage, jaundice, left ventricular dysfunction (outflow tract obstruction; in patients with sigmoid-shaped interventricular septum), leukopenia, pain, pancytopenia, pulmonary hemorrhage, pruritus, prolonged QT interval on ECG, skin rash, Stevens-Johnson syndrome, subcutaneous hemorrhage, subdural hematoma, thrombocytopenia, thrombosis, torsades de pointes, vasodilation, vomiting
Hypersensitivity to cilostazol or any component of the formulation; heart failure of any severity.
Concerns related to adverse effects:
• Cardiovascular effects: May induce tachycardia, palpitation, tachyarrhythmia, and/or hypotension. Left ventricular outflow tract obstruction has been reported in patients with sigmoid shaped interventricular septum; monitor for the development of a new systolic murmur or cardiac symptoms after initiating therapy.
• Hematologic effects: Cases of thrombocytopenia or leukopenia progressing to agranulocytosis, reversible upon discontinuation, have been reported when not immediately discontinued; monitor platelets and white blood cell counts periodically.
Disease-related concerns:
• Hemostatic disorders: Avoid use in patients with active pathological bleeding or hemostatic disorders (has not been studied).
• Cardiovascular disease: [US Boxed Warning]: Cilostazol is contraindicated in patients with heart failure of any severity. Phosphodiesterase inhibitors have caused decreased survival compared with placebo in patients with class III to IV heart failure. Patients with history of ischemic heart disease may be at increased risk for exacerbation of angina pectoris or myocardial infarction.
• Hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment (has not been studied).
• Renal impairment: Use with caution in patients with severe renal impairment.
Other warnings/precautions:
• Elective surgery: Time required to recover adequate platelet function is ~2 days (Hall 2011). Of note, bleeding times were not significantly altered by cilostazol after 3 to 14 days of treatment (Kim 2004; Wilhite 2003).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 50 mg, 100 mg
Yes
Tablets (Cilostazol Oral)
50 mg (per each): $1.82 - $1.93
100 mg (per each): $1.82
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer 30 minutes before or 2 hours after meals (breakfast and dinner).
Intermittent claudication: Reduction of symptoms of intermittent claudication, as indicated by an increased walking distance.
Elective PCI with bare metal or drug eluting stent placement (alternative agent); Secondary prevention of noncardioembolic ischemic stroke or transient ischemic attack (TIA)
Pletal may be confused with Plendil
Substrate of CYP1A2 (Minor), CYP2C19 (Major with inhibitors), CYP2C19 (Minor with inducers), CYP2D6 (Minor), CYP3A4 (Major with inhibitors), CYP3A4 (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Weak), ENT1 and CNT3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abciximab: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Abrocitinib: Agents with Antiplatelet Effects may increase antiplatelet effects of Abrocitinib. Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Anagrelide: May increase adverse/toxic effects of Cilostazol. Risk X: Avoid
Anticoagulants: Cilostazol may increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): Agents with Antiplatelet Effects may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Caplacizumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Caplacizumab. Specifically, the risk of bleeding may be increased. Risk C: Monitor
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase serum concentration of CarBAMazepine. Risk C: Monitor
Cladribine: Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transporters may increase serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration. Risk D: Consider Therapy Modification
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Collagenase (Systemic): Agents with Antiplatelet Effects may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP2C19 Inhibitors (Moderate): May increase serum concentration of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase active metabolite exposure of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP2C19. Monitor clinical response to cilostazol closely. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Dofetilide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Dofetilide. Risk C: Monitor
Esomeprazole: May increase active metabolite exposure of Cilostazol. Esomeprazole may increase serum concentration of Cilostazol. Risk C: Monitor
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Cilostazol. Management: Advise patients to avoid grapefruit juice when taking cilostazol. If patients regularly consume grapefruit juice, decrease the dose of cilostazol to 50 mg twice daily. Risk D: Consider Therapy Modification
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Limaprost: May increase adverse/toxic effects of Agents with Antiplatelet Effects. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider Therapy Modification
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
Obinutuzumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and agents with antiplatelet effects, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Omeprazole: May increase serum concentration of Cilostazol. Omeprazole may increase active metabolite exposure of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving omeprazole. Monitor clinical response to cilostazol closely. Risk D: Consider Therapy Modification
Pentosan Polysulfate Sodium: Agents with Antiplatelet Effects may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Riociguat: Cilostazol may increase hypotensive effects of Riociguat. Risk C: Monitor
Selumetinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Weak) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Thrombolytic Agents: Agents with Antiplatelet Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Ticlopidine: May increase serum concentration of Cilostazol. Ticlopidine may increase active metabolite exposure of Cilostazol. Risk C: Monitor
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider Therapy Modification
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vonoprazan: May increase serum concentration of Cilostazol. Risk C: Monitor
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Taking cilostazol with a high-fat meal may increase peak concentration by 90% and increase AUC by 25%. Grapefruit juice may increase serum levels of cilostazol and enhance toxic effects. Management: Administer cilostazol on an empty stomach 30 minutes before or 2 hours after meals. Concurrent ingestion of grapefruit juice may require therapy modification; consult drug interactions database for more detailed information.
Adverse events have been observed in animal reproduction studies.
It is not known if cilostazol is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
Platelets and WBC counts periodically; monitor for the development of a new systolic murmur or cardiac symptoms.
Cilostazol and its metabolites are inhibitors of phosphodiesterase III. As a result, cyclic AMP is increased leading to reversible inhibition of platelet aggregation, vasodilation, and inhibition of vascular smooth muscle cell proliferation.
Onset of action: Effect on walking distance: 2 to 4 weeks; may require up to 12 weeks
Protein binding: Cilostazol 95% to 98%; active metabolites: 66% to 97%
Metabolism: Hepatic; CYP1A2 (minor), CYP2C19 (major), CYP2D6 (minor), CYP3A4 (major).
Half-life elimination: ~11 to 13 hours
Excretion: Urine (74%) and feces (20%) as metabolites
Altered kidney function: Severe renal impairment increases active metabolite concentrations and alters protein binding of the parent drug.
Cigarette smoking: Exposure is decreased by ~20% in smokers.