PLETAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PLETAL (PLETAL).
Cilostazol inhibits phosphodiesterase III (PDE3), increasing cAMP levels in platelets and vascular smooth muscle, leading to platelet inhibition and vasodilation.
| Metabolism | Extensively metabolized via hepatic cytochrome P450 (CYP) 3A4 and to a lesser extent CYP2C19. |
| Excretion | Renal (approximately 77% as metabolites, <1% unchanged); fecal (approximately 18%) |
| Half-life | Terminal half-life of cilostazol is approximately 11-13 hours; for active metabolites 3,4-dehydro-cilostazol (about 4-6 times more active) half-life is similar. Steady state achieved within a few days. |
| Protein binding | 95-98% bound, primarily to albumin |
| Volume of Distribution | Not precisely determined in humans; estimated apparent Vd/F is approximately 2.5-3.0 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 100% (highly absorbed); food increases Cmax but decreases AUC by about 15%. |
| Onset of Action | Oral: Improvement in walking distance noted within 2-4 weeks of continuous therapy; maximal effect may require up to 12 weeks. |
| Duration of Action | Sustained improvement with chronic dosing; effects reversible upon discontinuation. Duration of action is continuous with twice-daily dosing. |
100 mg orally twice daily, administered at least 30 minutes before or 2 hours after meals.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl ≥25 mL/min). For severe renal impairment (CrCl <25 mL/min), use is not recommended due to increased exposure. |
| Liver impairment | No dosage adjustment for mild hepatic impairment (Child-Pugh A). For moderate to severe hepatic impairment (Child-Pugh B or C), use is contraindicated. |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied. |
| Geriatric use | No specific dose adjustment recommended; however, elderly patients may have increased sensitivity, and monitoring for adverse effects such as headache, diarrhea, and palpitations is advised. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PLETAL (PLETAL).
| Breastfeeding | Unknown if excreted into human breast milk; M/P ratio not determined. Studies in rats show excretion into milk. Risk to infant unclear, especially regarding antiplatelet effect and potential for bleeding. Weigh benefit of breastfeeding against maternal need for drug; use caution. Prolonged use may theoretically accumulate in infant due to limited metabolic capacity. |
| Teratogenic Risk | Pletaal (cilostazol) is classified as Pregnancy Category C. Animal studies have shown adverse effects at high doses, including increased fetal resorptions and decreased fetal weight in rats and rabbits. No adequate human studies exist; risk cannot be ruled out. First trimester: potential teratogenic effects unknown; avoid use. Second and third trimesters: possible fetal harm due to maternal hemorrhage risk (antiplatelet effect). Use only if benefit clearly outweighs risk. |
■ FDA Black Box Warning
Contraindicated in patients with heart failure of any severity (NYHA class II-IV) due to increased mortality observed in clinical trials.
| Serious Effects |
["Heart failure of any severity (NYHA class II-IV)","History of hemorrhagic stroke","Known hypersensitivity to cilostazol or any component of the formulation","Hemostatic disorders or active bleeding"]
| Precautions | ["Use with caution in patients with moderate to severe hepatic impairment or severe renal impairment","Increased risk of bleeding when co-administered with anticoagulants or antiplatelet agents","Potential for tachycardia, palpitations, and hypotension","Not recommended for use in patients with a history of hemorrhagic stroke"] |
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| Fetal Monitoring | Monitor maternal bleeding time (may prolong), CBC for thrombocytopenia, and signs of hemorrhage. Fetal: ultrasound for growth restriction and well-being if used in third trimester. Newborn: monitor for bruising, petechiae, or bleeding if used near delivery. |
| Fertility Effects | In animal studies, no adverse effects on fertility or reproductive performance were observed at clinically relevant doses. Human data lacking; theoretical effect from vascular smooth muscle relaxation unlikely. |