Drug interactions with cisapride: clinical implications.

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.
• 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.