Flash VIG-news: domperidone: no longer approved for use in children due to a lack of efficacy

The use of domperidone in newborns, infants, children (under 12) and adolescents weighing less than 35kg is no longer approved at European level. A new clinical study has demonstrated a lack of efficacy of the medical product.

Domperidone is a dopamine antagonist that is solely authorised for the relief of the symptoms of nausea and vomiting.

In 2013 and 2014, a European review was carried out on the cardiac risk associated with the use of domperidone. One of the recommendations resulting from this review, approved by the European Commission in July 2014, was a request to carry out a clinical study on its use in children in order to generate solid efficacy data for its only approved indication. This request notably arose due to the reduction of the recommended dose for newborns, infants, children (under 12) and adolescents weighing under 35kg from 0.25 to 0.5 mg/kg administered 3-4 times a day, to a maximum dosage of 0.25 mg/kg 3 times a day in order to reduce the cardiotoxicity risk.

The study was terminated early due to a lack of efficacy. Its results did not demonstrate any significant benefit compared to treatment with a placebo. As of now, the marketing authorisation holder of MOTILIUM®, the reference medicinal product, has offered to remove the indication of domperidone for newborns, infants, children (under 12) and adolescents weighing less than 35 kg. This proposal has been approved by the FAMHP and the other European member states concerned. Additional details concerning the aforementioned study are now included in section 5.1 “Pharmacodynamic properties” of MOTILIUM®’s summary of product characteristics (SPC).

As a result, the MOTILIUM® 1 mg/ml “paediatric” drinkable suspension with dosing pipette, the only product specifically targeted at the paediatric population aged under 12, shall be withdrawn from the market as of 15.09.2019.

Furthermore, the FAMHP would like to issue a reminder regarding the safety advice resulting from the conclusion of the European review completed in 2014 and still in effect:

Therapeutic indication:

Domperidone is solely indicated for the relief of the symptoms of nausea and vomiting.

Dosage:

Adults and adolescents (12 years and older, weighing at least 35 kg): 10 mg up to 3 times a day, with a maximum daily dose of 30 mg.

Domperidone must be used at the lowest effective dose for the shortest time necessary to control nausea and vomiting. The maximum duration of treatment should not usually exceed one week.

Contraindications:

Domperidone is contraindicated in the following situations:

  • in patients with moderate or severe hepatic impairment
  • in patients with known existing prolongation of cardiac conduction intervals, particularly the QTc interval, patients with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart failure
  • co-administration with QTc-prolonging medicinal products
  • co-administration with potent CYP3A4 inhibitors (regardless of their QT interval prolonging effects).

Special warnings and precautions for use:

During post-marketing surveillance, there have been very rare cases of QT interval prolongation and torsades de pointes in patients taking domperidone. These cases concern patients with risk factors, electrolyte abnormalities and concomitant treatments which may have been contributing factors.

Epidemiological studies showed that domperidone was associated with an increased risk of serious ventricular arrhythmias or sudden death. A higher risk was observed in patients older than 60 years, patients taking daily doses greater than 30 mg, and patients concurrently taking QT-prolonging medicinal products or CYP3A4 inhibitors.

More information

You can find out more about all DHPC on the FAMHP website.

SPCs and Patient Information Leaflets for all medicinal products authorised in Belgium are available on the FAMHP website.

Last updated on
18/04/2019