To evaluate the safety of domperidone in children.

Clinical studies involving domperidone used in children were searched from PubMed, Embase, Cochrane Library, Chinese Biology Medical disc, CNKI, VIP, and Wanfang Database. Adverse drug reaction information bulletins which were reported by WHO Pharmaceuticals Newsletter and National Center for adverse drug reaction monitoring were searched and adverse drug reactions (ADR)/adverse drug events (ADE) related to domperidone were collected. Websites of European Medicines Agency, Food and Drug Administration of United States, Medicines and Healthcare Products Regulatory Agency (MHRA), Health Canada, and Therapeutic Goods Administration were searched and information of risks and benefits related to domperidone treatment were collected. Randomized controlled trails (RCTs) were Meta-analyzed using RevMan 5.2 software and other data were descriptively analyzed. Correlation analysis of domperidone and adverse drug reactions was performed using evaluation criteria of WHO. Severity of ADR/ADE was evaluated using criteria CTCAE 4.03 of United States Department of Health and Human Services.

A total of 9 RCTs, 1 cohort study, 4 self-controlled studies, and 24 case reports were entered in this study. Meta-analysis of 9 RCTs showed the following results. There were no statistical significance in the incidence of ADR in children between the domperidone group and the control groups of placebo, cisapride, and mosapride. The incidence of ADR in children in the domperidone group was lower than that in the metoclopramide (RR=0.44, 95%CI: 0.23-0.86, P=0.02), and higher than that in the Traditional Chinese Medicine group (RR=16.09, 95%CI: 2.01-129.04, P=0.01). There were no serious adverse events of domperidone reported in the 9 RCTs. It was showed in the self-controlled study that oral domperidone was associated with QTc prolongation in neonates. One hundred and one cases of ADR were reported in 24 case reports. Of them, 80 cases (79.2%) of ADR were mild-to-moderate (CTCAE grading 1-2), 21 cases (20.8%) of ADR were severe (CTCAE grading 3), and no ADR with CTCAE grading 4-5 was reported. The results of causality assessment on above mentioned 101 cases of ADR showed that 2 cases of ADR were associated with domperidone certainly, 76 were probably, 15 cases of ADR induced by drug overdose, and 2 cases induced by combination use of medicines that may cause the same adverse reactions. In April 2014, European Medicines Agency suggested to limit clinical indications and dosage of domperidone. In September 2014, MHRA of Britain announced that domperidone was no longer to use as over-the-counter.

No enough evidences to prove that the incidence of ADR induced by domperidone was higher than that by the placebo, other gastro-kinetic agents, and other conventional treatments in children. The risks of serious ADR occurrence existed in children with domperidone treatment.

Domperidone; Child; Safety