title: Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine.
abstract: BACKGROUND
  Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agent. Oral domperidone is not approved in the United States, but it is used in many countries to treat nausea and vomiting, gastroparesis and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone.
  
  
  METHODS
  The authors undertook a review of the cardiac safety of oral domperidone.
  
  
  CONCLUSIONS
  The data from preclinical studies are unambiguous in identifying domperidone as able to produce marked hERG channel inhibition and action potential prolongation at clinically relevant concentrations. The compound's propensity to augment instability of action potential duration and action potential triangulation are also indicative of proarrhythmic potential. Domperidone should not be administered to subjects with pre-existing QT prolongation/LQTS, subjects receiving drugs that inhibit CYP3A4, subjects with electrolyte abnormalities or with other risk factors for QT-prolongation. With these provisos, it is possible that domperidone may be used as a galactogogue without direct risk to healthy breast feeding women, but more safety information should be sought in this situation. Also, more safety information is required regarding risk to breast feeding infants before domperidone is routinely used in gastroparesis or gastroesphageal reflux in children.
authors.affiliation: Queensland University of Technology, School of Biomedical Sciences, Faculty of Health , Brisbane, QLD4002 , Australia +61 7 3138 2015 ; +61 7 3138 1534 ; sheila.doggrell@qut.edu.au.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Doggrell
authors.forename: Jules C
authors.initials: JC
authors.lastname: Hancox
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000932:Antiemetics / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D004294:Domperidone / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D056669:Galactogogues / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006331:Heart Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D012307:Risk Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000932:Antiemetics; D056669:Galactogogues; D004294:Domperidone