Reported time to onset of neurological adverse drug reactions among different age and gender groups using metoclopramide: an analysis of the global database Vigibase®

Eur J Clin Pharmacol. 2018 May;74(5):627-636. doi: 10.1007/s00228-017-2407-z. Epub 2017 Dec 30.


Purpose: Despite FDA and EMA warnings of long-term use, little is known regarding the time to onset (TTO) of neurological adverse drug reactions (ADR) for metoclopramide. The aims of this study were, first, to evaluate whether neurological ADRs are more commonly reported for metoclopramide than for other medications, and second, to describe how time to onset of neurological ADRs differs by age and gender.

Methods: All ADR reports with metoclopramide as the suspected/interacting drug were extracted from the WHOs Global ADR database Vigibase® between 1967 and May 2016. Cox proportional hazards models were fit using TTO of neurological ADRs as the outcome and age, gender, and type of ADR as predictors. Proportional Reporting Ratios (PRRs) for neurological ADRs were compared across age and gender. Lawyer reports were excluded in the analysis.

Results: Over 47,000 ADR reports with metoclopramide were identified. Over one third (35.6%) of the reports came from lawyers. The majority of ADRs in general and neurological ADRs in specific occurred within the first 5 days of metoclopramide use (median 1 day). TTO increased with age. Neurological ADRs were reported two to four times as frequently for metoclopramide than for other drugs, with the highest PRRs observed in children (PRR = 4.24 for girls and 4.60 for boys).

Conclusions: Most adverse drug reactions occur within the first 5 days of treatment with metoclopramide. Patients requiring use of metoclopramide should be carefully monitored for neurological ADRs during the first days of treatment.

Keywords: Adverse drug reactions; Metoclopramide; Vigibase.

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems / statistics & numerical data
  • Antiemetics / adverse effects*
  • Child
  • Child, Preschool
  • Databases, Factual / statistics & numerical data
  • Dopamine D2 Receptor Antagonists / adverse effects*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Metoclopramide / adverse effects*
  • Middle Aged
  • Neurotoxicity Syndromes / epidemiology*
  • Pharmacovigilance
  • World Health Organization
  • Young Adult


  • Antiemetics
  • Dopamine D2 Receptor Antagonists
  • Metoclopramide