Domperidone for nausea and vomiting: lack of efficacy in children; reminder of contraindications in adults and adolescents

Domperidone is no longer licensed for use in children younger than 12 years or those weighing less than 35 kg. Results from a placebo-controlled study in children younger than 12 years with acute gastroenteritis did not show any difference in efficacy at relieving nausea and vomiting compared with placebo.

• From: Medicines and Healthcare products Regulatory Agency
• Published: 16 December 2019

• Therapeutic area: Cardiovascular disease and lipidology, GI, hepatology and pancreatic disorders, Paediatrics and neonatology

Advice for healthcare professionals:

Change of indication

• domperidone is now authorised for the relief of symptoms of nausea and vomiting only in adults and adolescents 12 years of age or older and weighing 35 kg or more
• consider alternative treatments to domperidone in children younger than 12 years of age who need relief of symptoms of nausea and vomiting

Reminder of contraindications

• European regulatory studies show that some physicians, including in the UK, are not aware of the important precautions for use of domperidone introduced in 2014
• domperidone is contraindicated:
  • in patients with moderate to severe hepatic impairment
  • in patients with known existing prolongation of cardiac conduction intervals (particularly QTc)
  • in patients with underlying cardiac diseases such as congestive heart failure,
  • in patients with significant electrolyte disturbances,
  • during co-administration with QT-prolonging drugs (for more information about considerations with apomorphine (see Drug Safety Update, April 2016)
  • during co-administration with potent CYP3A4 inhibitors (regardless of their QT-prolonging effects)
  • in patients with hypersensitivity to domperidone
  • in patients with a prolactin-releasing pituitary tumour
  • in patients in which stimulation of the gastric motility could be harmful (for example, in patients with gastro-intestinal haemorrhage, mechanical obstruction, or perforation)

Reminder of recommendations for dose and treatment duration

• for adults and adolescents 12 years of age or older and weighing 35 kg or more, the recommended maximum dose in 24 hours is 30 mg (dose interval: 10 mg up to 3 times a day)
• domperidone should be used at the lowest effective dose for the shortest possible duration and maximum treatment duration should not usually exceed 1 week
• report suspected adverse drug reactions associated with domperidone to the Yellow Card Scheme

Lack of efficacy in the paediatric population younger than 12 years

Domperidone is a dopamine antagonist with antiemetic properties. A European review of the safety of domperidone in 2014 introduced new restrictions following continued reports of cardiac side effects (see later section). At the time, there were limited data to support paediatric use in the relief of the symptoms of nausea and vomiting, and studies were requested to provide further data to support efficacy.

A multicentre, double-blind, randomised, placebo-controlled, parallel-group, prospective study^{[footnote 1]} evaluated the safety and efficacy of domperidone in 292 children with acute gastroenteritis aged between 6 months and 12 years (median age 7 years). In addition to oral rehydration treatment (ORT), patients were randomised to receive domperidone oral suspension at 0.25 mg/kg (up to a maximum of 30 mg domperidone per day), or placebo, 3 times a day, for up to 7 days. This study did not show domperidone suspension plus ORT to be significantly more effective than placebo plus ORT at reducing vomiting episodes during the first 48 hours after the first treatment administration.^{[footnote 1]} The study did not reveal any new safety concern.

A European review assessed this new evidence that domperidone is not as effective in this population as previously considered. Consequently, the product information for UK domperidone medicines has been updated to remove the indication in children younger than 12 years of age.

Domperidone is also used outside of its authorised indications in children in the UK for gastrokinetic effects in conditions other than nausea and vomiting. If a specialist physician considers, based on their professional judgement and available evidence of the medical condition, that domperidone use in any condition is justified in a child younger than 12 years, the patient or parent/caregiver should be fully informed of the potential benefits and risks of the different options (please see previous guidance on off-label use in Drug Safety Update, April 2009).

Reminder on the safe use of domperidone in accordance with the product information

The European safety review in 2014 confirmed risk of serious cardiac adverse drug reactions related to domperidone, including QTc prolongation, torsade de pointes, serious ventricular arrhythmia, and sudden cardiac death. The review concluded that additional risk minimising measures were necessary to improve the balance between benefits and risks and to reduce the risk of serious cardiac adverse events. More about these important restrictions, contraindications, and precautions can be found in the Drug Safety Update, December 2014.

Recent regulatory studies in several European countries, including the UK, show a proportion of physicians are not aware of the changes in indication and the contraindications introduced in 2014. All healthcare professionals are thus reminded to follow the precautions for safe use of domperidone-containing products (see list of contraindications).

Current usage of domperidone in the UK

Both tablet and oral suspension domperidone products are currently marketed in the UK. Data from the Clinical Practice Research Datalink (CPRD) suggest use of domperidone in the UK has reduced since 2014. Based on extrapolation from CPRD data, an estimated 5700–7500 children aged 0–11-years were prescribed domperidone in the UK in 2018 for any indication.^{[footnote 2]}

Article citation: Drug Safety Update volume 13, issue 5: December 2019: 1.

1. Leitz G, et al. Safety and efficacy of low-dose domperidone for treating nausea and vomiting due to acute gastroenteritis in children. J Pediatr Gastroenterol Nutr 2019; 69: 425–30. ↩ ↩²

2. The information presented here is based in part on data from the Clinical Practice Research Datalink however, the interpretation and conclusions regarding usage contained in this report are that of MHRA alone. ↩

Published 16 December 2019