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: Oral: 100 mg twice daily. Note: The American College of Chest Physicians recommends use when refractory to exercise therapy and smoking cessation; use in combination with either aspirin or clopidogrel (ACCP [Guyatt 2012]).
Note: Discontinue treatment if symptoms are not improved after 3 months of therapy.
PCI (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 (ACCP [Guyatt 2012]).
Secondary prevention of noncardioembolic stroke or TIA (off-label use): Oral: 100 mg twice daily. Note: Clopidogrel or aspirin/extended release dipyridamole recommended over the use of cilostazol (ACCP [Guyatt 2012]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary. Severe renal impairment increases metabolite concentrations; use with caution.
End-stage renal disease (ESRD) on dialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Not dialyzable (NCS/SCCM [Frontera 2016])
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 50 mg, 100 mg
Yes
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
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 (Hill 2011). Of note, bleeding times were not significantly altered by cilostazol after 3 to 14 days of treatment (Kim 2004; Wilhite 2003).
Substrate of CYP1A2 (minor), CYP2C19 (major), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Anagrelide: May enhance the adverse/toxic effect of Cilostazol. Risk X: Avoid combination
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Cladribine: Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins may increase the 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 the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration 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 the 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 the 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
Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Esomeprazole: May increase serum concentrations of the active metabolite(s) of Cilostazol. Esomeprazole may increase the serum concentration of Cilostazol. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the 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 enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the 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
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Omeprazole: May increase serum concentrations of the active metabolite(s) of Cilostazol. Omeprazole may increase the serum concentration 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: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Riociguat: Cilostazol may enhance the hypotensive effect of Riociguat. Management: Riociguat is contraindicated with nonselective phosphodiesterase (PDE) inhibitors and PDE type 5 inhibitors. Other types of PDE inhibitors are not contraindicated, but caution is advised and patients should be monitored for hypotension. Risk C: Monitor therapy
Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the 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 the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Ticlopidine: May increase serum concentrations of the active metabolite(s) of Cilostazol. Ticlopidine may increase the serum concentration of Cilostazol. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the 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
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
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 metabolite concentrations and alters protein binding of the parent drug.
Cigarette smoking: Exposure is decreased by ~20% in smokers.
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.
