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Related Experiment Videos

Drug interactions with cisapride: clinical implications.

E L Michalets1, C R Williams

  • 1Mission + St Joseph's Health System, Department of Pharmacy, Asheville, North Carolina 28801, USA. msj.cphelm@memo.msj.org

Clinical Pharmacokinetics
|August 5, 2000
PubMed
Summary

Cisapride, used for gastrointestinal disorders, can cause fatal arrhythmias by interacting with CYP3A4 inhibitors and drugs prolonging the QT interval. Avoid these combinations to minimize risks.

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Area of Science:

  • Pharmacology
  • Gastroenterology
  • Cardiology

Background:

  • Cisapride is a prokinetic agent for gastrointestinal disorders, notably GERD.
  • Significant risks of ventricular arrhythmias and deaths associated with cisapride use have been reported.
  • Understanding drug interactions is crucial for safe cisapride use under limited access protocols.

Purpose of the Study:

  • To review pharmacokinetic and pharmacodynamic interactions of cisapride with other drugs.
  • To provide clinical recommendations for avoiding potentially fatal cisapride-associated adverse events.
  • To identify risk factors for cisapride-induced arrhythmias.

Main Methods:

  • Literature review of published studies on cisapride interactions.
  • Analysis of pharmacokinetic interactions involving cytochrome P450 (CYP) 3A4 inhibition.

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  • Analysis of pharmacodynamic interactions related to QT interval prolongation.

    • Main Results:

    • CYP3A4 inhibitors (e.g., macrolide antibacterials, azole antifungals, some antidepressants, HIV protease inhibitors) increase cisapride plasma concentrations.
    • Concomitant use of cisapride with CYP3A4 inhibitors like clarithromycin, erythromycin, fluconazole, itraconazole, ketoconazole, nefazodone, fluvoxamine, and most HIV protease inhibitors is contraindicated.
    • Cisapride should not be used with drugs that prolong the QT interval (e.g., Class Ia/III antiarrhythmics, certain antipsychotics, tricyclic antidepressants) or in patients with uncorrected electrolyte disturbances.

    Conclusions:

    • Clinicians must be aware of cisapride's drug interaction profile to prevent serious cardiac events.
    • Avoiding coadministration with CYP3A4 inhibitors and QT-prolonging drugs is essential for patient safety.
    • Careful patient selection and monitoring are necessary for cisapride use under restricted protocols.