What is the recommended dose of Cilostazol (Pletal) for intermittent claudication?

Cilostazol Dosage for Intermittent Claudication

The recommended dose of cilostazol (Pletal) for intermittent claudication is 100 mg orally twice daily, which is more effective than the 50 mg twice daily dosage. 1, 2

Dosing and Administration

• Cilostazol 100 mg twice daily is indicated as an effective therapy to improve symptoms and increase walking distance in patients with lower extremity peripheral arterial disease (PAD) and intermittent claudication 2
• In dose-ranging trials, cilostazol administered at 100 mg twice daily was more effective than 50 mg twice daily 2
• A therapeutic trial of cilostazol should be considered in all patients with lifestyle-limiting claudication 2
• Patient tolerance should be assessed at 2-4 weeks and benefit evaluated within 3-6 months to determine if long-term therapy will be beneficial 3

Efficacy

• Cilostazol improves maximal walking distance by 40% to 60% compared with placebo after 12 to 24 weeks of therapy 2, 1
• Cilostazol also improves pain-free walking distance by approximately 59% 1, 4
• FDA clinical studies showed that across eight clinical trials, the improvement in maximal walking distance in patients treated with cilostazol 100 mg twice daily ranged from 28% to 100% 5
• Improvements in walking performance were seen across various subpopulations including those defined by gender, smoking status, diabetes mellitus, duration of PAD, age, and concomitant medication use 5

Mechanism of Action

• Cilostazol is a phosphodiesterase type 3 inhibitor that increases cyclic adenosine monophosphate 2
• It has vasodilator and platelet inhibitory properties 2, 3
• Cilostazol modestly increases ankle-brachial index (ABI), though this hemodynamic effect does not fully account for the improvement in claudication symptoms 2, 3

Important Contraindications

• Cilostazol is absolutely contraindicated in patients with heart failure of any severity 1, 6
• The FDA has mandated a black box warning that cilostazol should not be used in patients with heart failure due to concerns about increased mortality risk associated with phosphodiesterase III inhibitors in this population 2, 6
• Always assess for heart failure before prescribing cilostazol 1, 6

Common Side Effects

• The most common side effects include headache, diarrhea, abnormal stools, palpitations, and dizziness 2, 4
• Approximately 20% of patients discontinue cilostazol within 3 months due to side effects 1, 3
• Adverse events are generally mild to moderate in intensity and often transient 7

Alternative Medications

• Pentoxifylline (400 mg three times daily) may be considered as a second-line alternative to cilostazol, but its clinical effectiveness is marginal and not well established 2, 1
• Cilostazol has been shown to be superior to pentoxifylline in improving walking distance 3, 7

Treatment Algorithm

1. First-line therapy: Supervised exercise training (30-45 minutes, at least 3 times weekly for minimum 12 weeks) 1
2. First-line pharmacotherapy: Cilostazol 100 mg twice daily for all patients with lifestyle-limiting claudication without heart failure 2, 1
3. Second-line pharmacotherapy: Consider pentoxifylline 400 mg three times daily if cilostazol is not tolerated or contraindicated 2, 1

Remember that combination therapy with exercise and cilostazol may provide additive benefits for patients with claudication 1.