Metoclopramide-containing medicines
- Procedure started
- Under evaluation
- CHMP opinion
- European Commission final decision
Table of contents
Overview
European Medicines Agency recommends changes to the use of metoclopramide
Changes aim mainly to reduce the risk of neurological side effects
On 24 October the European Medicines Agency's Committee on Medicinal Products for Human Use (CHMP) confirmed previously recommended changes to the use of metoclopramide-containing medicines in the European Union (EU), including restricting the dose and duration of use of these medicines to minimise the known risks of potentially serious neurological (brain and nerve) side effects. This followed a re-examination, at the request of a marketing authorisation holder, of the opinion originally given by the Committee on 26 July 2013.
Metoclopramide-containing medicines have been authorised separately in individual Member States of the EU, with differing licensed indications such as nausea and vomiting of various causes (for example after treatment with anticancer chemotherapy or radiotherapy, after surgery, or associated with migraine) and gastrointestinal motility disorders (conditions in which the normal passage of food through the gut is delayed).
The original review of metoclopramide was carried out at the request of the French medicines regulatory agency (ANSM), following continued safety concerns over side effects and concerns over efficacy. ANSM asked the CHMP to review the benefits and risks of these medicines in all age groups and to recommend consistent indications across the EU. The review confirmed the well-known risks of neurological effects such as short-term extrapyramidal disorders, a group of involuntary movement disorders that may include muscle spasms (often involving the head and neck) and tardive dyskinesia (uncontrollable movements such as grimacing and twitching). The risk of acute (short-term) neurological effects is higher in children, although tardive dyskinesia is reported more often in the elderly, and the risk is increased at high doses or with long-term treatment. The evidence indicated that these risks outweighed the benefits of metoclopramide in conditions requiring long-term treatment. There have also been very rare cases of serious effects on the heart or circulation, particularly after injection.
During the re-examination the Committee confirmed its recommendation that metoclopramide should only be authorised for short-term use (up to 5 days), that it should not be used in children below 1 year of age and that in children over 1 year of age it should only be used as a second-choice treatment (after other treatments have been considered or tried) for the prevention of delayed nausea and vomiting after chemotherapy and for the treatment of post-operative nausea and vomiting. In adults, the Committee recommended use for the prevention and treatment of nausea and vomiting such as that associated with chemotherapy, radiotherapy, surgery and in the management of migraine. In addition, the maximum recommended doses in adults and children should be restricted, and higher strength formulations, including oral liquids in strengths above 1 mg/ml, removed from the market. Such oral liquids have been associated with overdose in children.
At the request of a manufacturer of higher strength oral solutions, the Committee reconsidered the evidence behind its view that oral solutions above 1 mg/ml should no longer be available, and the arguments and proposals to minimise the risk that were supplied by the company, specifically a restriction on the use of the higher strength solution in children. However, the CHMP concluded that although liquid dose forms had some benefits, such as easier adjustment of doses in patients with reduced kidney or liver function, the 1 mg/ml solution could be used in situations where a liquid dosage form was appropriate, and the Committee was not convinced the proposed restrictions would be sufficient to reduce the risk of error and overdose in children. Although it had been suggested adult doses would be difficult to give accurately as a 1 mg/ml solution because of the large number of drops required, there should be no problem if the Committee's recommendation were followed that liquid dose forms be given by a measuring device such as a graduated oral syringe.
Detailed recommendations for patients and healthcare professionals are available below.
The CHMP recommendation was then sent to the European Commission, which adopted it with a final legally binding decision, valid throughout the European Union (EU), on 20 December 2013.
Key facts
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About this medicine
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| Approved name |
Metoclopramide-containing medicines
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| International non-proprietary name (INN) or common name |
metoclopramide
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| Associated names |
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| Class |
Anti-emetic
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About this procedure
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| Current status |
European Commission final decision
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| Reference number |
EMEA/H/A-31/1321
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| Type | |
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Key dates and outcomes
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| CHMP opinion date |
24/10/2013
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| EC decision date |
20/12/2013
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All documents
Opinion provided by Committee for Medicinal Products for Human Use
European Commission final decision
Metoclopramide Article-31 referral - Annex I (PDF/462.91 KB)
First published: 31/01/2014
Last updated: 31/01/2014
Metoclopramide Article-31 referral - Annex II (PDF/114.25 KB)
First published: 31/01/2014
Last updated: 31/01/2014
Metoclopramide Article-31 referral - Annex III (PDF/299.4 KB)
First published: 31/01/2014
Last updated: 31/01/2014
Description of documents published
Please note that some of the listed documents apply only to certain procedures.
- Overview - lay-language summary of the stage of the procedure
- Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
- Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
- List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
- Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
- List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
- List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
- Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
- Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
- Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
- Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
- Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
- Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
- Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
- Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)
Note that older documents may have different titles.