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The Safety of Metoclopramide in Children: A Systematic Review and Meta-Analysis

Abstract

Introduction

Metoclopramide is recommended for adults with breakthrough or refractory chemotherapy-induced nausea and vomiting (CINV) and for CINV prophylaxis in children. The drug regulatory agencies of Canada and the EU have revised the labelling of metoclopramide to contraindicate its use in children aged <1 year and to caution against its use in children aged <5 years and its duration of use beyond 5 days.

Objective

This review describes the safety of metoclopramide in children when given for any indication.

Methods

We conducted electronic searches in MEDLINE and Embase as of 9 March 2015. All studies in English reporting adverse effects associated with the use of metoclopramide in children (aged ≤18 years) were included. Adverse effects that had a cumulative incidence of at least 1 % and were reported in prospective studies were synthesized.

Results

A total of 108 (57 prospective) studies involving 2699 patients (2745 metoclopramide courses) were included. The most common adverse effects reported in prospective studies of metoclopramide in children were extrapyramidal symptoms (EPS; 9 %, 95 % confidence interval [CI] 5–17), diarrhea (6 %, 95 % CI 4–9), and sedation (multiple-dose studies: 6 %, 95 % CI 3–12). Dysrhythmia, respiratory distress/arrest, neuroleptic malignant syndrome, and tardive dyskinesia were rarely associated with metoclopramide use.

Limitations

The definitions of adverse effects reported in the included studies were heterogeneous, and the risk of bias in most studies was moderate.

Conclusions

The most commonly reported adverse effects associated with the use of metoclopramide in children—EPS, diarrhea, and sedation—were reversible and of no long-term significance. Adverse effects that were life threatening or slow to resolve were rarely associated with its use in children.

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Acknowledgments

The assistance of Ms. Elizabeth Uleryk, Library Scientist, with the literature search and the administrative assistance of Ms. Sandra Cabral are gratefully acknowledged.

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Correspondence to L. Lee Dupuis.

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Funding

Support of the Pediatric Oncology Group of Ontario to conduct the study and to prepare the manuscript is acknowledged. The funder did not influence the interpretation of the results of this work.

Conflict of interest

Melissa Lau Moon Lin, Paula D. Robinson, Jacqueline Flank, Lillian Sung, and L. Lee Dupuis have no conflicts of interest that are directly relevant to the content of this study.

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Lau Moon Lin, M., Robinson, P.D., Flank, J. et al. The Safety of Metoclopramide in Children: A Systematic Review and Meta-Analysis. Drug Saf 39, 675–687 (2016). https://doi.org/10.1007/s40264-016-0418-9

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Keywords

  • Dystonia
  • Metoclopramide
  • Tardive Dyskinesia
  • Gastroparesis
  • Neuroleptic Malignant Syndrome