CMDh confirms recommendations on restricting use of domperidone-containing medicines
Press release
European Commission to take final legal decision
The Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) has endorsed recommendations to restrict the use of domperidone-containing medicines. The CMDh, a medicines regulatory body representing the EU Member States, agreed that these medicines should only be used to relieve symptoms of nausea and vomiting, that doses and length of treatment should be restricted and that they should be adjusted carefully by the patient's weight where available for use in children. The recommendations were originally made by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) at its meeting of 3-6 March, after a careful evaluation of the available evidence on the benefits and risks of such medicines.
Domperidone-containing medicines have been authorised nationally in individual Member States of the EU for the treatment of nausea and vomiting of various causes but also for the management of symptoms such as bloating, discomfort and heartburn.
The review of domperidone was carried out at the request of the Belgian medicines authority over concerns about the medicine's effects on the heart. The injectable form of domperidone was withdrawn in 1985 because of such side effects. Serious effects on the heart with domperidone, including prolongation of the QT interval (an alteration of the electrical activity of the heart) and arrhythmias (unstable heartbeats), have previously been evaluated by the EMA and the product information updated with relevant warnings. However, cases of heart problems in patients using the medicine continued to be reported, and the PRAC was therefore asked to examine whether the benefits still outweighed the risks for these medicines in their approved uses and forms, and whether their marketing authorisations should be maintained or changed across the EU.
The CMDh confirmed by majority the PRAC recommendation that domperidone-containing medicines should remain available and may continue to be used in the EU for the management of the symptoms of nausea and vomiting, but that the recommended dose should be reduced to 10 mg up to three times daily by mouth for adults and adolescents weighing 35 kg or more. These patients may also be given the medicine as suppositories of 30 mg twice daily. Products licensed in children and adolescents weighing less than 35 kg should be given by mouth at a dose of 0.25 mg per kg bodyweight up to three times daily. Measuring devices should be included with liquid formulations to allow accurate dosing by bodyweight. The medicine should not normally be used for longer than one week.
Domperidone should no longer be authorised to treat other conditions such as bloating or heartburn. It must not be given to patients with moderate or severe impairment of liver function, or in those who have existing abnormalities of electrical activity in the heart or heart rhythm, or who are at increased risk of such effects. In addition, it should not be used with other medicines that have similar effects on the heart or reduce the breakdown of domperidone in the body (thus increasing the risk of side effects). The product information should be amended appropriately. Products supplying a dose of 20 mg by mouth, and suppositories of 10 or 60 mg are no longer recommended for use and should be withdrawn, as should combination products with cinnarizine (an antihistamine) where available.
Although the scope of the review does not cover use outside the licensed indications (off-label use) the principles behind these recommendations should be considered whenever domperidone is used.
As the CMDh position was adopted by majority vote, the CMDh position will now be sent to the European Commission, which will take an EU-wide legally binding decision.
Information to patients
Information to healthcare professionals
These recommendations are based on careful consideration of data on the safety and efficacy of domperidone from various sources. This comprised non-clinical and clinical data, both published and unpublished, including a thorough QT study, cumulative review of case reports of cardiac disorders and vascular investigations from the safety databases for domperidone products, pharmacoepidemiological studies, and published and unpublished efficacy studies.
More about the medicine
Domperidone-containing medicines have been authorised in most EU Member States via national procedures since the 1970s and are widely available as over-the-counter or prescription-only medicines. They are available as tablets, oral suspension and suppositories under various trade names (such as Motilium). A combination product with cinnarizine (an antihistamine) is available in some Member States for the treatment of motion sickness.
Domperidone works by blocking receptors for the neurotransmitter dopamine found in the gut and in the part of the brain linked to vomiting. This helps to prevent nausea (feeling sick) and vomiting.
More about the procedure
The review of domperidone was initiated on 1 March 2013 at the request of the Belgian medicines authority, the Federal Agency for Medicines and Health Products (FAGG-AFMPS), under Article 31 of Directive 2001/83/EC.
A review of these data was first conducted by the Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC recommendations were sent to Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which adopted a final position. The CMDh, a body representing EU Member States, is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.
As the CMDh position was adopted by majority vote, the CMDh position will now be sent to the European Commission, which will take an EU-wide legally binding decision.