Summary Safety Review - Metoclopramide - Abnormal Involuntary Movements of the Body (Extrapyramidal Symptoms) in Children
Review decision
A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.
Issued: 2015-01-15
issue
A safety review was initiated to evaluate the currently available information regarding the possible risk of abnormal involuntary movements of the body, known as extrapyramidal symptoms (EPS), in children taking the recommended daily dose of metoclopramide. This review was prompted by a report published by the European Medicines Agency which found that the development of EPS was common in children taking metoclopramide at the recommended daily dose. Prior to this report, the possibility of EPS in children was believed to mostly occur at doses greater than recommended.
Background
Approved use of metoclopramide in Canada
Metoclopramide has been on the Canadian market for decades. It was introduced under the brand name MAXERAN in 1974. At the time of this review, it was sold by 5 generic companies.a
In Canada, metoclopramide is approved for the treatment of conditions such as slowed stomach emptying and for medical procedures like inserting a tube into the small intestine (called small bowel intubation). The recommended daily dose for children (0.5 mg/kg/day) is provided in the prescribing information for metoclopramide. At the time of the review, the prescribing information for metoclopramide included warnings on the risk of EPS in children taking more than the recommended daily dose. They contained limited information on the risk of EPS in children taking the recommended daily dose.
Extrapyramidal symptoms
EPS refer to a variety of abnormal involuntary movements caused by a malfunctioning of the part of the brain responsible for the movements of the body. Although they are mostly reversible, EPS also include a condition called tardive dyskinesia (TD), which is serious and may be permanent. TD is a repetitive, involuntary movement which affects mainly the face, tongue, arms and legs. TD is rare in children.
Objective
To assess the available evidence concerning the possible risk of EPS in children treated with metoclopramide at the recommended daily dose. This review considered information from Canadian adverse reaction reports, scientific literature, international safety data, as well as what is known about the use of these products both in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.
Key findings
Use of metoclopramide in Canadab
Metoclopramide is not widely used to treat children in Canada. In 2011-2012, major reasons for prescribing metoclopramide in children included the treatment of inflammation of the esophagus (esophagitis), headache, nausea and vomiting. In 2012, metoclopramide use in children represented 3% of 419,000 prescriptions for metoclopramide in Canada.
Canadian reports of extrapyramidal symptoms in children taking the recommended daily dose of metoclopramide
At the time of this review, Health Canada had identified 8 reports of EPS suspected of being associated with metoclopramide in children receiving the recommended daily dose.
Scientific reports
There is limited information on the safety of metoclopramide in children in the scientific literature. Most articles described studies on the effect of metoclopramide (called efficacy studies).
A review of the available scientific information on EPS and the use of metoclopramide in children showed that EPS can occur in children taking recommended daily doses of metoclopramide. Children younger than one year of age appear to be at higher risk of EPS.
International data
A review of the European data found many cases of EPS in children less than 18 years of age treated with metoclopramide. Most cases occurred when recommended doses were used.
At the time of this review, several other countries had restricted the use of metoclopramide in children.
Conclusions and actions
The safety review showed that EPS can occur in children treated with metoclopramide at the recommended daily dose (0.5 mg/kg/day). It also showed that metoclopramide should not be used in children less than one year of age. Finally, the risk of EPS should be considered with the expected benefits of metoclopramide use in children older than one year of age.
In order to reduce the risks associated with metoclopramide use in children, Health Canada has worked with the manufacturers of metoclopramide to incorporate the following information in their prescribing information:
- Metoclopramide is contraindicated in children less than one year of age;
- Metoclopramide should not be used in children greater than one year of age unless the expected benefits clearly outweigh the possible risks; and
- EPS may also occur in children receiving the recommended daily dose of metoclopramide, which should not exceed 0.5 mg/kg/day.
Health Canada has also issued a communication to inform healthcare professionals and patients about the risk of EPS at recommended doses of metoclopramide and changes to the prescribing information.
References
- European Medicines Agency. Rapporteur's Public Paediatric Assessment Report for paediatric studies submitted in accordance with Article 45 of Regulation (EC) No1901/2006, as amended; 2010.
- Council of International Organizations of Medical Sciences (CIOMS). Reporting adverse drug reactions: definition of terms and criteria for their use; 1999.
Footnotes
- Metoclopramide is currently sold by 4 generic companies.
- IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place.
- This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review.