Prescriber Update Articles

Cisapride and Arrhythmias

Web site: November 1999
Prescriber Update No.19:22-23

Medsafe Editorial Team

Cisapride (Prepulsid™) causes QT-prolongation which may worsen to life-threatening torsade de pointes. The WHO database holds 159 reports of these events. Many patients were taking interacting medicines, most commonly erythromycin, fluconazole, clarithromycin and amiodarone. Excessive dose and electrolyte disturbances also featured in the cases.
Cisapride should be avoided with substances which inhibit cytochrome P450 3A4, with other agents which prolong the QT-interval, in patients with predisposing factors for arrhythmia or pre-existing QT-prolongation and in patients with hepatic failure.

Cisapride can cause QT-prolongation

An article published in Prescriber Update in February 1997 advised of the possibility of QT-prolongation with cisapride (Prepulsid™). At that time it was not possible to be confident of the causal association. Since that time further data, including clinical studies, have become available confirming the association.

159 reports of QT-prolongation and/or torsade de pointes in WHO database

At the end of July 1999, the WHO database held 159 reports of QT-prolongation and/or torsade de pointes with cisapride. 82 of these cases involved torsade de pointes. Death was the outcome in 11 cases. In around half of the cases the patient was taking an interacting medicine, most commonly erythromycin, fluconazole, clarithromycin and amiodarone. Excessive dose and electrolyte disturbances were factors in a small number of cases.

Avoid cisapride with interacting medicines or predisposing conditions

Cisapride should be avoided in the following circumstances:

• With use of agents inhibiting metabolism by cytochrome P450 3A4: macrolide antibiotics (erythromycin, clarithromycin, etc.), azole antifungals (ketoconazole, itraconazole, fluconazole, etc), protease inhibitors (ritonavir, indinavir, etc.), nefazodone and grapefruit juice
  
• With use of agents which may prolong the QT-interval, quinine, terfenadine, some antiarrhythmic medicines (e.g. amiodarone, quinidine, flecainide, sotolol), tricyclic antidepressants (e.g. amitriptyline) and some antipsychotic agents (phenothiazines and haloperidol)
  
• In patients with a history of QT-prolongation, ventricular arrhythmia, torsade de pointes, and those with risk factors for arrhythmia, such as second or third degree atrioventricular block, clinically significant heart disease, uncorrected electrolyte disturbances, renal or respiratory failure
  
• In patients with hepatic failure.

Cardiac arrhythmias and cisapride are an adverse reaction of current concern. Please report all New Zealand cases to the Centre for Adverse Reactions Monitoring, University of Otago, PO Box 913, Dunedin.