Domperidone Restrictions Endorsed in EU Due to Cardiac Risk

Megan Brooks


April 25, 2014

The European Medicines Agency's (EMA's) Coordination Group for Mutual Recognition and Decentralised Procedures (CMDh) has endorsed recommendations to restrict the use of domperidone-containing antiemetics because of concerns about adverse cardiac effects, the EMA announced today.

The CMDh agreed these medicines should only be used to relieve symptoms of nausea and vomiting, doses and duration of use should be restricted, and doses 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The recommendations were originally made by the EMA's Pharmacovigilance Risk Assessment Committee in March, as reported by Medscape Medical News.

Domperidone-containing drugs are authorized in the European Union for treatment of nausea and vomiting of various causes, including in children in some member states, and also for the management of symptoms of bloating, discomfort, and heartburn. The US Food and Drug Administration has not approved domperidone for any indication.

"The benefit-risk balance of domperidone remains positive in the relief of the symptoms of nausea and vomiting. The available evidence of efficacy was not sufficient to support its use for other indications," the EMA said in a news release issued April 25, announcing the CMDh position.

A review of the evidence confirms a "small increased risk" for serious adverse cardiac events with domperidone use, including QTc prolongation, torsade de pointes, serious ventricular arrhythmia, and sudden cardiac death, the EMA said. They note that a higher risk is seen in patients older than 60 years, adults taking daily oral doses of more than 30 mg, and those taking QT-prolonging medicines or CYP3A4 inhibitors concomitantly.

The CMDh confirmed by majority the Pharmacovigilance Risk Assessment Committee recommendation that domperidone-containing drugs should remain available and may continue to be used for the management of the symptoms of nausea and vomiting, but that the recommended dose should be reduced to 10 mg up to 3 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.

The CMDh also agreed that domperidone products licensed for use in children and adolescents weighing less than 35 kg should be given by mouth at a dose of 0.25 mg/kg bodyweight up to 3 times daily, that measuring devices should be included with liquid formulations to allow accurate dosing by body weight, and that the medicine should not normally be used for longer than 1 week.

The CMDh also agreed that domperidone should not be used to treat other conditions such as bloating or heartburn and should not be given to patients with moderate or severe impairment of liver function, those who have existing abnormalities of electrical activity in the heart or heart rhythm, or those at increased risk for 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 for adverse effects).

The CMDh also agreed that products supplying a dose of 20 mg by mouth and suppositories of 10 or 60 mg should no longer be 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," the EMA said.

The CMDh position will now be sent to the European Commission, which will make a European Union–wide, legally binding decision.


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