Morris Amy D, Chen Jennifer, Lau Elaine, Poh Jennifer
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.
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.
Can J Hosp Pharm. 2016 May-Jun;69(3):224-30. doi: 10.4212/cjhp.v69i3.1560. Epub 2016 Jun 30.
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.
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.
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.
Original research included in this review reported on the cardiac-related safety of domperidone in nononcologic patients under 18 years of age.
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.
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.
多潘立酮是一种用于治疗小儿胃食管反流病的促动力药。加拿大卫生部已发布警告，提示多潘立酮相关的室性心律失常和心源性猝死风险增加。然而，支持该警告的数据仅涉及成年患者；因此，将这些安全风险外推至儿科患者存在困难。
总结和评估多潘立酮相关的QT间期延长、室性心律失常和心源性猝死的证据，以确定该药物对儿科患者的安全性。
检索了两个数据库（MEDLINE [1946年至2015年8月] 和Embase [1980年至2015年8月]），使用了以下医学主题词和关键词：“多潘立酮”、“心律失常，心脏性”、“死亡，猝死，心脏性”、“心电图”、“心脏病”、“长QT综合征”、“心动过速，室性”、“尖端扭转型室速”和“心室颤动”。检索限于针对18岁以下人群开展且以英文发表的研究。
本综述纳入的原始研究报告了多潘立酮在18岁以下非肿瘤患者中的心脏相关安全性。
在符合纳入标准的5项研究（n = 137例患者）中，有1项报告校正QT（QTc）间期有统计学意义的变化，但临床意义不明。大多数研究报告在少数患者中罕见病理性QTc间期。然而，未始终考虑混杂因素（如电解质水平异常或同时使用的药物）。心电图（ECG）评估者实施盲法可能减轻了潜在偏倚；然而，并非始终如此。纳入研究的设计不允许评估因果关系。对结果的解释应谨慎。
尽管现有证据有限，但在少数婴儿中观察到病理性QTc间期，这支持多潘立酮相关的QT间期延长风险的可能性。由于QT间期延长的潜在严重性，对于接受多潘立酮治疗的患者应进行个体评估并常规监测心电图。
