What are the contraindications of cilostazol (Pletal) in patients with heart failure and other medical conditions?

Contraindications of Cilostazol (Pletal)

Cilostazol is absolutely contraindicated in patients with heart failure of any severity due to increased risk of mortality, as well as in patients with hemostatic disorders, active pathologic bleeding, and hypersensitivity to the medication. 1

Absolute Contraindications

• Heart Failure:

  • Contraindicated in patients with congestive heart failure of any severity (Class III: Harm) 2, 1
  • The FDA has mandated a black box warning against cilostazol use in heart failure patients 3, 2
  • This contraindication is based on the drug's mechanism as a phosphodiesterase III inhibitor, which has shown excess mortality in similar patients 2

• Bleeding Disorders:

  • Contraindicated in patients with hemostatic disorders or active pathologic bleeding 1
  • This includes bleeding peptic ulcers and intracranial bleeding 1
  • The contraindication is related to cilostazol's reversible platelet aggregation inhibition properties 1

• Hypersensitivity:

  • Contraindicated in patients with known or suspected hypersensitivity to any of its components 1

Drug Interactions and Precautions

• CYP450 Inhibitors:

  • Significant drug interactions occur when cilostazol is coadministered with:
    • CYP3A4 inhibitors (e.g., erythromycin, diltiazem) 4
    • CYP2C19 inhibitors (e.g., omeprazole) 4
  • In Europe, cilostazol is contraindicated in patients receiving these inhibitors 4
  • In the US, dosage reduction is recommended during coadministration 4

• Severe Renal or Hepatic Impairment:

  • Cilostazol is extensively metabolized by CYP450 enzymes with excretion of metabolites in the urine 3
  • The half-life is prolonged in patients with severe renal impairment 3
  • Use with caution in severe hepatic or renal impairment 4

Mechanism Behind Contraindications

Cilostazol is a 2-oxoquinolone derivative with vasodilatory and antiplatelet properties. As a phosphodiesterase III inhibitor, it increases intracellular cyclic AMP, which:

1. Can potentially trigger ventricular tachycardia in heart failure patients 3
2. Accounts for its vasodilatory effects 3
3. Contributes to its antiplatelet and antithrombotic properties 4

Common Side Effects to Monitor

• Headache (occurs in up to 25% of patients within first 2 weeks) 3
• Gastrointestinal side effects 3
• Diarrhea, abnormal stools, palpitations, and dizziness 3, 4

Clinical Implications

Despite the black box warning for heart failure, a text-mining study of electronic medical records found no association between cilostazol use and increased cardiovascular mortality, even in patients with CHF who were prescribed the medication despite its warning 5. However, this observational evidence does not override the FDA contraindication, which remains in effect based on the known mechanism of action and experience with similar drugs.

For patients with peripheral arterial disease who cannot take cilostazol due to contraindications, alternative management strategies include supervised exercise programs, risk factor modification, antiplatelet therapy, and consideration of revascularization for severely limiting symptoms 2.