Domperidone: limited benefits with significant risk for sudden cardiac death

J Cardiovasc Pharmacol. 2013 Mar;61(3):218-25. doi: 10.1097/FJC.0b013e31827afd0d.

Abstract

Background: Domperidone (antinausea/vomiting agent) was recently shown by several groups to increase sudden cardiac death (SCD). Drug-induced disturbances of cardiac repolarization may be a major mechanism.

Methods and results: Experiments were executed in isolated female rabbit hearts perfused for 150 minutes with domperidone 30, 60, or 100 nM. Domperidone significantly prolonged the action potential duration: +9% at 30 nM, +32% at 60 nM, and +48% at 100 nM. Domperidone induced significant disturbances of repolarization in 83% of hearts at 60 nM and in 100% at 100 nM, including early afterdepolarizations and polymorphic ventricular tachycardia. Maximum therapeutic free drug plasma concentration of domperidone (19 nM) yields a safety index of only ∼2.5, that is, 12-fold below the accepted minimum. Gastrointestinal benefits and risks for SCD were derived from the literature. The defined daily dose of domperidone (30 mg/day) fails to show unequivocal gastrointestinal benefits beyond a placebo effect. In contrast, 5 of 5 population-based studies show that oral domperidone significantly increases the odds ratio for SCD to 2.8 (1.53-6.21) and it increases sharply above 30 mg/day.

Conclusions: Because domperidone has placebo-like benefits but is associated with increased SCD and a narrow safety margin, it should not be used in medicine.

Publication types

  • Review

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Antiemetics / adverse effects*
  • Antiemetics / pharmacology
  • Antiemetics / therapeutic use
  • Death, Sudden, Cardiac / etiology*
  • Domperidone / adverse effects*
  • Domperidone / pharmacology
  • Domperidone / therapeutic use
  • Dopamine Antagonists / adverse effects*
  • Dopamine Antagonists / pharmacology
  • Dopamine Antagonists / therapeutic use
  • Dyspepsia / drug therapy
  • Dyspepsia / physiopathology
  • Electrocardiography / drug effects
  • Female
  • Gastroesophageal Reflux / drug therapy
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / physiopathology
  • Heart / drug effects*
  • Humans
  • In Vitro Techniques
  • Male
  • Osmolar Concentration
  • Perfusion
  • Rabbits
  • Reproducibility of Results
  • Risk Assessment
  • Severity of Illness Index
  • Tachycardia, Ventricular / chemically induced

Substances

  • Antiemetics
  • Dopamine Antagonists
  • Domperidone