Overview

Metoclopramide is generally indicated for the prevention of nausea and vomiting associated with chemotherapy or radiotherapy and symptomatic treatment of nausea and vomiting in adults. In children above one (1) year old, metoclopramide is only indicated as second line therapy for the prevention of delayed chemotherapy-induced and post-operative nausea and vomiting.¹

Metoclopramide crosses the blood-brain barrier and is associated with serious neurological adverse events, mainly oculogyric crisis and other related symptoms which are of particular concern in children.²

Oculogyric crisis is uncontrolled ocular muscles characterised by marked involuntary deviation of the eyes. The eyes usually inadvertently move upward and to the left or right, and it can change position from crisis to crisis.³

Background

Following a safety review by NPRA on the benefit-risk ratio of the drug in 2015, the Drug Control Authority (DCA) had issued a directive [Ref. No.: Bil. (24) dlm.BPFK/PPP /07/25] for product registration holders to update metoclopramide package inserts with restrictions in its indication and dose. These restrictions include a new contraindication of metoclopramide use in patients aged below one year old, and limitation of usage in patients aged between 1-18 years old as a second-line option.⁴ Following this directive, NPRA has released a latest safety issue notification to healthcare professionals. This safety issue was also highlighted in MADRAC Newsletter August 2015.⁵

Adverse Drug Reaction (ADR) Reports

Since the last safety issue notification in 2015, the NPRA has received 897 reports with 1,591 adverse events suspected to be related to metoclopramide. The total number of neurologic adverse events reported is 361, with the most reported being oculogyric crisis (241, 66.7%). There was one (1) report of oculogyric crisis received involving a six (6) months old infant.⁶

Advice for Healthcare Professionals

• Metoclopramide (oral and injection) is contraindicated in children aged below one (1) year old, while metoclopramide suppository is contraindicated in children aged below 18 years old.
• For children, treatment duration should not exceed five (5) days for the prevention of post-chemotherapy nausea and vomiting, and should not exceed 48 hours for the prevention of post-operative nausea and vomiting.
• Be alert on the risk of oculogyric crisis when prescribing metoclopramide especially in paediatric patients.
• Consider an alternative treatment if it is indicated and available.
• Report all adverse events suspected to be related to metoclopramide to NPRA.

References

1. National Pharmaceutical Regulatory Agency. Malaysian Product Registration Database (Quest 3+). Metoclopramide local product package insert [Internet]. Last revision date: 2018 January [Cited 2020 June 16]. Available from: https://npra.gov.my/index.php/en/consumers/information/products-search
2. Drug Bank Canada. Metoclopramide [Internet]. Last revision date: 2020 June 22 [Cited 2020 June 16]. Available from: https://www.drugbank.ca/drugs/DB01233
3. Gold DR. Eye Movement Disorders: Conjugate Gaze Abnormalities. Liu, Volpe, and Galetta's Neuro-Ophthalmology (Third Edition), Diagnosis and Management [Internet]. 2019 [Cited 2020 June 16] p549-584. Available from: https://doi.org/10.1016/B978-0-323-34044-1.00016-X.
4. National Pharmaceutical Regulatory Agency. Direktif untuk Semua Produk Metoclopramide: Memperketatkan Indikasi dan Mengehadkan Dos Penggunaan Berikutan Risiko Kesan Advers Neurologik [Ref. No.: Bil. (24) dlm.BPFK/PPP/07/25]. 2015 January 8 [Cited 2020 June 16]. Available from: https://www.npra.gov.my/images/Drug-Registration-Guidance-Document/January-2015/Direktif_Bil-17_metoclopramide.pdf
5. National Pharmaceutical Regulatory Agency. MADRAC Newsletter August 2015 [Internet]. 2015 August [Cited 2020 June 16]. Available from: https://www.npra.gov.my/images/Publications/Newsletter_MADRAC_Bulletin/Bulletin_MADRAC_Aug2015.pdf
6. National Pharmaceutical Regulatory Agency. The Malaysian Adverse Drug Reactions database [Internet]. 2020 [Cited 2020 June 16].

DISCLAIMER:

This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.