Together for Short Lives
Call the Helpline 0808 8088 100

Domperidone-Associated QT Interval Prolongation in Non-oncologic Pediatric Patients: A Review of the Literature

Journal title
The Canadian journal of hospital pharmacy
Publication year
2016
Author(s)
Morris, A. D.; Chen, J.; Lau, E.; Poh, J.
Pages
224-30
Volume
69
Number
3

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. DATA SOURCES: 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. STUDY SELECTION AND DATA EXTRACTION: Original research included in this review reported on the cardiac-related safety of domperidone in nononcologic patients under 18 years of age. DATA SYNTHESIS: 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. Publisher: CONTEXTE: La domperidone est un agent gastroprocinetique utilise pour traiter le reflux gastro-oesophagien chez l’enfant. Sante Canada a publie des mises en garde a propos d’un risque accru d’arythmies ventriculaires et de mort subite cardiaque associees a la domperidone. Or, comme les donnees probantes ne concernent que l’adulte, il est difficile de generaliser les risques pour la sante a l’enfant. OBJECTIF: Resumer et analyser les donnees probantes portant sur l’allongement de l’intervalle QT, les arythmies ventriculaires et la mort subite cardiaque associes a la domperidone afin de determiner le degre d’innocuite du medicament chez l’enfant. SOURCES DES DONNEES: Deux bases de donnees (MEDLINE [1946 a aout 2015] et EMBASE [1980 a aout 2015]) ont ete interrogees en utilisant les mots cles et les Medical Subject Headings (MeSH) suivants : << domperidone >> (domperidone), << arrhythmias, cardiac >> (arythmies cardiaques), << death, sudden, cardiac >> (mort, subite, cardiaque), << electrocardiography >> (electrocardiographie), << heart diseases >> (cardiopathies), << long QT syndrome >> (syndrome du QT long), << tachycardia, ventricular >> (tachycardie, ventriculaire), << torsades de pointes >> (torsades de pointes) et << ventricular fibrillation >> (fibrillation ventriculaire). La recherche se limitait aux etudes publiees en anglais et effectuees chez l’humain de moins de 18 ans. SELECTION DES ETUDES ET EXTRACTION DES DONNEES: Les etudes retenues dans la presente revue abordaient l’innocuite cardiaque de la domperidone chez les patients de moins de 18 ans qui ne sont pas atteints d’un cancer. SYNTHESE DES DONNEES: Parmi les cinq etudes qui repondaient aux criteres d’inclusion (n = 137 patients), une indiquait un changement statistiquement significatif dans l’intervalle QT corrige (QTc), mais la signification clinique demeurait floue. La plupart des etudes signalaient de rares cas d’intervalles QTc pathologiques chez un nombre limite de patients. Cependant, des facteurs de confusion (desequilibre electrolytique ou emploi concomitant de medicaments, par exemple) n’etaient pas systematiquement pris en compte. Il aurait ete possible d’eviter de potentiels biais en tenant les lecteurs d’electrocardiogramme (ECG) dans l’ignorance du traitement, mais cette mesure n’etait pas toujours mise en oeuvre. Les plans des etudes retenues ne permettaient pas d’evaluer la causalite. Il faut donc interpreter les resultats avec prudence. CONCLUSIONS: Bien qu’il n’y ait que peu de donnees probantes, des cas d’intervalles QTc pathologiques ont ete releves chez un petit nombre de nourrissons, ce qui vient appuyer le risque possible d’allongement de l’intervalle QTc associe a la domperidone. A cause de la potentielle gravite de l’allongement de l’intervalle QT, une evaluation individuelle et une surveillance ECG systematique doit etre mise en place pour les patients qui recoivent de la domperidone. fre

Research abstracts