Cilostazol
Cilostazol
Generic Name
Cilostazol
Mechanism
- Selective inhibition of PDE3 → ↑ intracellular cyclic‑adenosine monophosphate (cAMP).
- Vasodilation: cAMP relaxes vascular smooth muscle in both arterial and venous beds, improving limb perfusion.
- Antiplatelet effect: Elevated cAMP inhibits platelet aggregation by reducing thromboxane A₂ production.
- The dual action decreases skeletal‑muscle ischemia while protecting against thrombotic events.
Pharmacokinetics
| Parameter | Value & Notes |
| Route | Oral, tablets (3 h p.o.) |
| Bioavailability | ~0.35 (intrinsic factor 5‑HT₄ mediated sequestration) |
| Peak concentration (Tₘₐₓ) | 1 – 3 h post‑dose |
| Half‑life | 5 – 8 h (dose‑dependent; ~8 h in liver impairment) |
| Metabolism | Hepatic, via CYP1A1, 1A2, 2C9, 2D6, 3A4 (no clinically active metabolite) |
| Excretion | Renal (≈35%) and biliary: unchanged drug and metabolites |
| Protein binding | 12 % (low, minimal impact on drug interactions) |
| Special Populations |
• Mild‑moderate renal impairment: no dose adjustment needed; < 25 % displays longer retention. • Severe renal impairment (CrCl < 15 mL min⁻¹): use with caution or avoid. • Hepatic impairment: dose reduction (50 %) should be considered. |
Indications
- Intermittent claudication secondary to PAD after conservative therapy (exercise, revascularization, lifestyle change).
- Improvement of walking distance and quality of life in symptomatic patients.
- Additionally used off‑label for vascular angina and to reduce claudication frequency in certain symptomatic PAD trials.
Contraindications
| Contraindication | Reason |
| Severe heart failure | Vasodilatory effect may worsen symptoms. |
| Active peptic ulcer disease or GI bleed | Antiplatelet action increases bleeding risk. |
| Hypersensitivity | Type I hypersensitivity reactions. |
| Pregnancy & lactation | Category C; teratogenic in animals; not recommended. |
| Severe hepatic impairment | Metabolic pathway limited. |
| Recent thrombotic event (e.g., MI, stroke < 3 months) | “Higher bleed toxicity” in early post‑events. |
Warnings:
• Bleeding: When combined with warfarin or dual antiplatelet therapy (aspirin + clopidogrel), risk increases; monitor INR/bleeding signs.
• Renal dysfunction: Accumulation of parent drug may enhance toxicity.
• Diabetes: Improved microvascular blood flow may transiently alter glucose reads; monitor blood glucose.
• Alcohol use: Concomitant use potentiates CYP450 inhibition—monitor for side effects.
Dosing
- Starting Dose: 100 mg orally twice daily (BID).
- Adult Indications: 100 mg × 2 days = 200 mg daily.
- Renal Impairment (CrCl 30–49 mL min⁻¹): 100 mg once daily (QD); no use if CrCl 2 weeks of therapy without benefit.
Adverse Effects
Common (≥ 5 %):
• Headache, nausea, diarrhea, palpitations, mild tremor, dizziness, flushing, edema (often lower extremities).
Serious (≤ 1 %):
• GI ulceration, intracranial hemorrhage, severe arrhythmias (ventricular fibrillation or torsade de pointes), clinically significant bleeding, sudden vision loss from retinal artery occlusion.
Rare (≤ 0.1 %):
• Acute heart failure exacerbation, hepatic dysfunction, increased lipogenesis, electrolyte imbalance.
Monitoring
| Parameter | Frequency | Purpose |
| ECG and heart rate | Baseline, then 1–2 weeks, additional if tachycardia develops | Monitor arrhythmia risk |
| Blood pressure | Baseline, yearly | Detect hypotension or orthostatic changes |
| Complete blood count | Baseline, 1 month, then quarterly | Identify anemia from GI bleeding |
| Liver function tests | Baseline, 1 month, then 6‑month | Hepatotoxicity surveillance |
| Renal function (CrCl) | Baseline, 1 month, then 6‑month | Adjust dosing for clearance |
| Bleeding signs | Continuous | Prompt cessation if overt bleed |
| Walking distance (Borg scale) | 1 month, then quarterly | Efficacy assessment |
Clinical Pearls
- Efficacy timing: Initiate cilostazol within 2 weeks of claudication onset to maximize improvement; delaying > 6 weeks reduces benefit.
- Contraindication nuance: Even mild heart failure (NYHA I–II) should be avoided; alternative agents (e.g., pentoxifylline) may be preferable.
- Bleeding caution: Use single‑agent cilostazol in patients requiring anticoagulation—adjust timing of INR checks.
- Cost & accessibility: Generic formulations are widely available, reducing health‑system burden while maintaining efficacy.
- Drug interactions: Ketoconazole and Cimetidine modestly increase plasma levels; warfarin additive effects may occur.
- Adjunct therapy: When combined with supervised exercise, cilostazol can lead to additive walking distance improvements—consider a 12‑week “exercise + cilostazol” program.
- Special population: In patients with Polycythemia Vera, cilostazol’s vasodilatory effect can precipitate hematologic complications; avoid concurrent usage.
- Monitoring of side‑effect severity: Early mild palpitations should prompt ACE‑inhibitor monitoring; consider cardio‑protective beta‑blockers if arrhythmias arise.
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• *For comprehensive dosing, safety, and regulatory updates, always refer to the most current prescribing information and institutional guidelines.*