title: Domperidone-Associated QT Interval Prolongation in Non-oncologic Pediatric Patients: A Review of the Literature.
abstract: BACKGROUND
  Domperidone is a prokinetic agent used to treat pediatric gastroesophageal reflux disease. Health Canada has issued warnings about an increased risk of domperidone-associated ventricular arrhythmias and sudden cardiac death. However, the supporting data referred only to adult patients; therefore, extrapolating the safety risks to pediatric patients is difficult.
  
  
  OBJECTIVE
  To summarize and evaluate the evidence for domperidone-associated QT interval prolongation, ventricular arrhythmias, and sudden cardiac death to determine the safety of this drug for pediatric patients.
  
  
  METHODS
  Two databases (MEDLINE [1946 to August 2015] and Embase [1980 to August 2015]) were searched with the following Medical Subject Headings and keywords: "domperidone", "arrhythmias, cardiac", "death, sudden, cardiac", "electrocardiography", "heart diseases", "long QT syndrome", "tachycardia, ventricular", "torsades de pointes", and "ventricular fibrillation". The search was limited to studies conducted in humans under 18 years of age and published in English.
  
  
  METHODS
  Original research included in this review reported on the cardiac-related safety of domperidone in nononcologic patients under 18 years of age.
  
  
  RESULTS
  Of the 5 studies meeting the inclusion criteria (n = 137 patients), one reported a statistically significant change in the corrected QT (QTc) interval, but the clinical significance was unclear. Most of the studies reported rare occurrences of pathological QTc intervals in a limited number of patients. However, confounding factors (e.g., abnormal electrolyte level or concurrent medications) were not consistently considered. Potential bias might have been alleviated by blinding of electrocardiogram (ECG) assessors; however, this was not consistently implemented. The designs of the included studies did not allow assessment of causality. The results should be interpreted with caution.
  
  
  CONCLUSIONS
  Although the available evidence is limited, pathological QTc intervals were noted among a small number of infants, which supports the possibility of domperidone-associated risk of prolonged QTc interval. Because of the potential severity of QT interval prolongation, individual assessment and routine ECG monitoring should be implemented for patients receiving domperidone.
authors.affiliation: BSP, ACPR, PharmD, was, at the time of this study, a Post-Baccalaureate PharmD student in the Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario. She is now with the College of Pharmacy and Nutrition, University of Saskatchewan, and the Saskatchewan Cancer Agency, Saskatoon, Saskatchewan.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Morris
authors.affiliation: BScPhm, PharmD, ACPR, is with the Drug Information Service of The Hospital for Sick Children and the Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chen
authors.affiliation: RPh, BScPhm, PharmD, MSc, ACPR, is with the Drug Information Service of The Hospital for Sick Children and the Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario.
authors.forename: Elaine
authors.initials: E
authors.lastname: Lau
authors.affiliation: BScPhm, PharmD, ACPR, is with the Department of Pharmacy, The Hospital for Sick Children, Toronto, Ontario.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Poh
keywords: QT interval prolongation; arrhythmia; domperidone; pediatrics