Cracking the Case on Sudden Cardiac Death and Domperidone

Posted by CorDynamics on April 18th, 2013

by Liomar Neves, Senior Scientist

Recently, the Journal of Cardiovascular Pharmacology published an original article investigating sudden cardiac death and QT interval prolongation associated with domperidone that caught the attention of our CorDynamics team.

The Report

Domperidone is a dopamine receptor antagonist not approved by FDA for sale in the US market, but is widely used in more than 100 countries. Its purported benefits are as a gastrointestinal prokinetic agent, an anti-nausea and vomiting therapeutic and more recently it has been used to promote lactation.

However, the compound has been associated with disturbances in ventricular electrophysiology. These include increases in QT interval and cardiac rhythm disturbances.

In this recent preclinical study, the authors confirm that domperidone prolongs action potential duration and suggests that the IC50 for blocking the hERG channel IKr may be lower than previously reported.

New Evidence

The study also involved the use of prolonged domperidone exposure times, longer cycle lengths to examine reverse-use dependence, and use of rabbit hearts that are naturally heightened for sensitivity to IKr antagonism.

  • Evidence demonstrated domperidone to have a high affinity to IKr and low safety margin, thus increasing risk of drug-induced long QT syndrome and potential proarrhythmogenesis.
  • Additionally, the report brings attention to the limited benefits of domperidone for gastrointestinal disturbances and highlights the risk of using a low safety margin drug for a non-threatening target such as promotion of lactation.

The authors concluded the report by urging other regulatory agencies to take the FDA’s approach and ban domperidone’s use.

Leave a Reply