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(sigh-low-stay-zol)
Pletal
Class: Antiplatelet agent

 Action Quinolinone derivative that inhibits cellular phosphodiesterase and exhibits a higher specificity for phosphodiesterase III.

 Indications Reduction of symptoms of intermittent claudication as indicated by an increased walking distance.

 Contraindications CHF of any severity; hypersensitivity to any components of the product. 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-IV CHF.

 Route/Dosage

Intermittent Claudication

PO 100 mg twice daily, taken ³ 30 minutes before or 2 hours after breakfast and dinner. Consider a dose of 50 mg twice daily during coadministration of such inhibitors of CYP3A4 and CYP2C19.

 Interactions

Aspirin: Short-term (£ 4 days) coadministration of aspirin with cilostazol showed a 23% to 35% increase in inhibition of ADP-induced ex vivo platelet aggregation compared with aspirin alone. Diltiazem: Diltiazem increased cilostazol plasma concentrations by » 53%. Initiate therapy at half the recommended dose. Macrolides: Erythromycin increased cilostazol Cmax by 47% and AUC by 73%. Other macrolide antibiotics would be expected to have similar effects. Initiate therapy at half the recommended dose. Omeprazole: Coadministration of omeprazole did not significantly affect the metabolism of cilostazol, but the systemic exposure to 3,4–dehydro-cilostazol was increased by 69%, probably the result of omeprazole’s potent inhibition of CYP2C19. Initiate therapy at half the recommended dose. P450 system: Cilostazol could have pharmacokinetic interactions because of effects of other drugs on its metabolism by CYP3A4 or CYP2C19. Platelet function inhibitors: Cilostazol could have pharmacodynamic interactions with other platelet function inhibitors.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Palpitations; tachycardia. CNS: Dizziness; vertigo. GI: Abnormal stool; diarrhea; dyspepsia; flatulence; nausea. RESP: Increased cough; pharyngitis; rhinitis. OTHER: Abdominal pain; back pain; headache; infection; myalgia; peripheral edema.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy in children have not been established. Cardiovascular risk: Cilostazol in contraindicated in patients with CHF.

PATIENT CARE CONSIDERATIONS

 Administration/Storage

  • Store at room temperature in a nonmoist environment (59 to 86°F).
  • Administer 30 min before or 2 hours after meals.
  • Do not administer with grapefruit juice. Avoid concurrent use due to food/drug interaction.
  • Do not administer to patient with any type of CHF.
  • Do not administer to patient with a hypersensitivity to cilostazol or any of its active ingredients.
  • Administer with caution to patients with renal, liver, or coagulation impairment.
  • Administer with caution to patients on other anticoagulant medications.

 Assessment/Interventions

  • Obtain a complete drug history of both prescription and nonprescription drugs.
  • Assess patient for potential drug interactions especially with those drugs metabolized by the P450 enzyme system especially CYP3A4 and 2C19 (eg, erythromycin, fluconazole, ketoconazole, itraconazole, omeprazole).
  • Monitor patient for signs of hypersensitivity, adverse, and therapeutic reactions.
  • Assess smokers for signs of therapy effectiveness.
  • Assess patient for adverse cardiac signs and symptoms and signs of CHF.
  • Monitor patient for signs and symptoms of bleeding, especially those concurrently on other anticoagulants.

 Patient/Family Education

  • Instruct patient to take cilostazol as directed and to read the patient package insert before starting therapy or restarting therapy.
  • Advise patient to inform primary care provider if taking or planning to take any otc medications, as there is potential for drug interactions.
  • Advise patient that beneficial effects of cilostazol may not be immediate as relief of symptoms may require > 2–12 wk.
  • Instruct patient to avoid consuming grapefruit juice to avoid drug/food interactions.
  • Advise smokers of risks, including potential interaction with the drug, and the benefits of not smoking.
  • Warn patient of the uncertainty concerning the cardiovascular risk with long-term use or for the patient with underlying heart disease. Instruct patient to report adverse cardiac symptoms immediately to primary care provider before continuing next dose
  • Advise patient not to take aspirin or any other NSAID without informing the primary care provider
  • Instruct patient to inform the primary care giver of any adverse reactions.
  • Warn women with childbearing potential to avoid becoming pregnant and apprise them of the potential hazard to the fetus.
  • Warn nursing mothers of the danger of transferring the drug to the baby through mother’s milk and possible infant effects. A decision to discontinue the drug or nursing should be made in collaboration with the primary health care provider.
  • Instruct patient to report any unusual reaction or concern to the primary care provider.

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