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

  • Pharmacoepidemiology and Prescription
  • Published:
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Abstract

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.

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Acknowledgements

The authors would like to thank the Uppsala Monitoring Centre (UMC), WHO’s Collaborating Centre for International Drug Monitoring that provided and gave permission to use the data analyzed in the present study. The opinions and conclusions, however, are not those of the UMC or of the WHO.

Author information

Authors and Affiliations

  1. Hospital Pharmacy of Tromsø, Sykehusapotek Nord HF, Norway, Postboks 6147 Langnes, 9291, Tromsø, Norway

    Kristian Svendsen

  2. Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, School of Pharmacy & PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway

    Mollie Wood, Erika Olsson & Hedvig Nordeng

  3. Department of Child Health, Norwegian Institute of Public Health, Oslo, Norway

    Hedvig Nordeng

Authors
  1. Kristian Svendsen
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  2. Mollie Wood
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  4. Hedvig Nordeng
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Corresponding author

Correspondence to Kristian Svendsen.

Ethics declarations

Ethical statement

Since the data received by the UMC is de-identified and furthermore the UMC did not provide any potentially identifiable variables such as narratives or patient initials, no ethical approval was needed.

Disclaimer

The WHO database contains summary reports of individual suspected adverse reactions to medicines, received from national centers in countries participating in the WHO International Drug Monitoring Programme. No causality assessment is made at the Uppsala Monitoring Centre. Since these reports constitute suspicions of adverse drug reactions, further investigation and research is needed for a full interpretation of the data.

Conflict of interest

The authors declare they have no conflict of interest.

Additional information

Key findings:

• For patients aged 45 and older, the reported time to onset for ADRs was longer than for younger patients, particularly for reports of tardive dyskinesia.

• Almost all ADRs occurred within the first 5 days of metoclopramide treatment initiation.

• A higher proportion of reported ADRs were neurological for metoclopramide compared to other medicines, regardless of age and gender.

• More than one third of all ADR reports were communicated by US lawyers after FDA warnings in 2009.

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Svendsen, K., Wood, M., Olsson, E. et al. 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 74, 627–636 (2018). https://doi.org/10.1007/s00228-017-2407-z

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