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Domperidone: Limited Benefits With Significant Risk for Sudden Cardiac Death

Hondeghem, Luc M. MD, PhD

Journal of Cardiovascular Pharmacology: March 2013 - Volume 61 - Issue 3 - p 218–225
doi: 10.1097/FJC.0b013e31827afd0d
Original Article
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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.

Department of Pharmacology, Catholic University of Leuven, Leuven, Belgium.

Reprints: Luc M. Hondeghem, Westlaan 85, B-8400 Oostende, Belgium (e-mail: luc.hondeghem@screenqt.com).

The authors report no conflicts of interest.

Received September 05, 2012

Accepted October 25, 2012

© 2013 by Lippincott Williams & Wilkins.