title: Domperidone: limited benefits with significant risk for sudden cardiac death.
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.
  
  
  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.
authors.affiliation: Department of Pharmacology, Catholic University of Leuven, Leuven, Belgium. luc.hondeghem@screenqt.com
authors.forename: Luc M
authors.initials: LM
authors.lastname: Hondeghem
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000932:Antiemetics / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004294:Domperidone / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D004415:Dyspepsia / Q000188:drug therapy / Q000503:physiopathology; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000503:physiopathology; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D010477:Perfusion; D011817:Rabbits; D015203:Reproducibility of Results; D018570:Risk Assessment; D012720:Severity of Illness Index; D017180:Tachycardia, Ventricular / Q000139:chemically induced
chemical_list: D000932:Antiemetics; D018492:Dopamine Antagonists; D004294:Domperidone