CILOSTAZOL
Clinical safety rating: avoid
Contraindicated (not allowed)
Selective phosphodiesterase 3 (PDE3) inhibitor, leading to increased intracellular cAMP in platelets and vascular smooth muscle, resulting in inhibition of platelet aggregation and vasodilation.
| Metabolism | Extensively metabolized in the liver via cytochrome P450 (CYP) enzymes, primarily CYP3A4 and CYP2C19, and to a lesser extent CYP1A2. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP2C19; 74% excreted in urine (30% as unchanged drug and 44% as metabolites) and 20% in feces via bile. |
| Half-life | Terminal elimination half-life is approximately 11-13 hours (range 10-15 h) in healthy subjects; prolonged in severe renal impairment (CrCl <25 mL/min) to 20-25 h, and in hepatic impairment. |
| Protein binding | 95-98% bound to plasma proteins, primarily to albumin (95%) and to alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 2.0-2.6 L/kg, indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral bioavailability is approximately 90% (absolute); food increases Cmax by 67% and AUC by 17% (high-fat meal), but does not significantly alter clinical effect. |
| Onset of Action | Oral: Clinical improvement in intermittent claudication symptoms (increased walking distance) typically observed within 2-4 weeks of continuous therapy. |
| Duration of Action | Sustained effect with continuous dosing; therapeutic benefit persists with ongoing administration. Discontinuation may result in return of claudication symptoms within days to weeks. |
100 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for GFR >25 mL/min; contraindicated if GFR ≤25 mL/min. |
| Liver impairment | Contraindicated in moderate to severe hepatic impairment (Child-Pugh class B or C). |
| Pediatric use | Not recommended; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required, but monitor for adverse effects due to age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 or CYP2C19 inhibitors (eg omeprazole) may increase levels Contraindicated in patients with heart failure of any severity.
| Breastfeeding | It is unknown whether cilostazol is excreted in human breast milk. In animal studies, cilostazol and its metabolites were detected in rat milk. The M/P ratio is not known. Due to the potential for adverse effects in nursing infants (including bleeding risk and cardiac effects), breastfeeding is not recommended during cilostazol therapy. |
| Teratogenic Risk | Cilostazol is classified as FDA Pregnancy Category C. In animal studies, it caused increased fetal resorptions, decreased fetal weights, and skeletal abnormalities at doses 2-5 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Specific trimesters: First trimester: risks include spontaneous abortion and malformations; second and third trimesters: risks include low birth weight and possible premature delivery due to inhibition of platelet aggregation. |
■ FDA Black Box Warning
Contraindicated in patients with congestive heart failure (CHF) of any severity; increased mortality observed in patients with CHF.
| Common Effects | Headache |
| Serious Effects |
Congestive heart failure (any severity), coagulation disorders (e.g., active bleeding, bleeding diathesis), history of hemorrhagic stroke, concurrent use of two or more antiplatelet/anticoagulant agents, severe renal impairment (CrCl <25 mL/min), moderate to severe hepatic impairment, known hypersensitivity to cilostazol.
| Precautions | Contraindicated in CHF; use with caution in patients with arrhythmias, bleeding risk, renal or hepatic impairment; avoid use in patients with moderate to severe hepatic impairment; monitor for palpitations, tachycardia, and hypotension. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of bleeding (e.g., bruising, petechiae). Monitor fetal growth and well-being via ultrasound if prolonged exposure during pregnancy. Assess for signs of premature labor. Monitor infant for bleeding complications if exposure occurs near delivery. |
| Fertility Effects | In animal studies, cilostazol did not impair fertility in male and female rats at doses up to 3-5 times the maximum human dose. However, no human studies are available. The drug is a phosphodiesterase 3 inhibitor with potential effects on reproductive organ blood flow; theoretical risk of reduced fertility due to impaired sperm function? Not established. |