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

Domperidone: limited benefits with significant risk for sudden cardiac death.

Author information

1
Department of Pharmacology, Catholic University of Leuven, Leuven, Belgium. luc.hondeghem@screenqt.com

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.

PMID:
23188128
DOI:
10.1097/FJC.0b013e31827afd0d
[Indexed for MEDLINE]

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