(sil OH sta zol)
Intermittent claudication: Reduction of symptoms of intermittent claudication, as indicated by an increased walking distance.
Hypersensitivity to cilostazol or any component of the formulation; heart failure of any severity
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. 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 with concomitant medications:
CYP2C19 inhibitors (eg, fluconazole, omeprazole, ticlopidine): Reduce cilostazol to 50 mg twice daily
Strong or moderate CYP3A4 inhibitors (eg, diltiazem, erythromycin, itraconazole, ketoconazole): Reduce cilostazol to 50 mg twice daily
Refer to adult dosing.
CrCl ≥25 mL/minute: No dosage adjustment necessary (Mallikaarjun, 1999).
CrCl <25 mL/minute: No dosage adjustment necessary (Mallikaarjun, 1999). 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); however, high protein binding makes removal by dialysis unlikely.
Mild impairment: No dosage adjustment necessary (Bramer, 1999).
Moderate to severe impairment: There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied); use with caution.
Oral: Administer 30 minutes before or 2 hours after meals (breakfast and dinner).
Store at 25 ‚ °C (77 ‚ °F); excursions are permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Pletal: 50 mg [DSC], 100 mg [DSC]
Generic: 50 mg, 100 mg
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy
Anagrelide: May enhance the adverse/toxic effect of Cilostazol. Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. 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. Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. 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. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP2C19 Inhibitors: May increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4. Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving strong inhibitors of CYP3A4. 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. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. 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. Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification
HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy
Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. Consider therapy modification
Luliconazole: May increase the serum concentration of CYP2C19 Substrates. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. 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. Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
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. Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. 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. Monitor therapy
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Platelets and WBC counts periodically
>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%), 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%) , chills (<2%), insomnia (<2%), malaise (<2%), neuralgia (<2%)
Dermatologic: Ecchymoses (<2%), skin hypertrophy (<2%), urticarial (<2%), xeroderma (<2%)
Endocrine & metabolic: Albuminuria (<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%), gastritis (<2%), gastroenteritis (<2%), gingival hemorrhage (<2%), hematemesis (<2%), melena (<2%), peptic ulcer (<2%), periodontal abscess (<2%)
Genitourinary: Cystitis (<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: 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%)
<2% (Limited to important or life-threatening): Agranulocytosis, anaphylaxis, aplastic anemia, cerebral hemorrhage, cerebrovascular accident, coronary thrombosis (stent), gastrointestinal hemorrhage, granulocytopenia, hematoma (extradural), hepatic insufficiency, hyperglycemia, hypersensitivity, hypertension, interstitial pneumonitis, intracranial hemorrhage, jaundice, leukopenia, prolonged Q-T interval on ECG, pancytopenia, pulmonary hemorrhage, Stevens-Johnson syndrome, subcutaneous hemorrhage, subdural hematoma, thrombocytopenia, thrombosis, torsades de pointes
Severe renal impairment increases metabolite concentrations and alters protein binding of the parent drug.
Dialysis: It is unlikely that cilostazol can be removed efficiently by dialysis because of its high protein binding (has not been studied).
Cigarette smoking: Exposure is decreased by ~20% in smokers.
Concerns related to adverse effects:
- Cardiovascular effects: May induce tachycardia, palpitation, tachyarrhythmia, and/or hypotension.
- 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: Cilostazol has not been studied in patients with active pathological bleeding or hemostatic disorders; avoid use in these patients.
- Cardiovascular disease: [US Boxed Warning]: The use of this drug is contraindicated in patients with heart failure of any severity. Phosphodiesterase inhibitors have decreased survival rates in patients with class III-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 (CrCl <25 mL/minute).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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).
C
Adverse events have been observed in animal reproduction studies.
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.
Hepatic; CYP1A2 (minor), CYP2C19 (major), CYP2D6 (minor), CYP3A4 (major)
Urine (74%) and feces (20%) as metabolites
Effect on walking distance: 2 to 4 weeks; may require up to 12 weeks
~11 to 13 hours
Cilostazol 95% to 98%; active metabolites 66% to 97%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dizziness, headache, diarrhea, abnormal stools, nausea, abdominal pain, pharyngitis, or rhinorrhea. Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), signs of infection, angina, severe dizziness, passing out, tachycardia, arrhythmia, or swelling of arm or leg (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.