Advice

Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in July 2013. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.

Summary

Only 1 small (n=22) partially blinded, randomised crossover study was identified. It found domperidone had a statistically significant benefit in the short term for improving gastric emptying times in very low birth weight preterm neonates receiving enteral feeds. No relevant studies were found in children and young people. This study provides only very limited evidence on the effectiveness, safety and tolerability of domperidone when used for promoting tolerance of enteral feeds in either the short or longer term.

Regulatory status: Off-label.

Effectiveness

  • One small study (n=22) reporting on gastric emptying times as a primary outcome:

    • domperidone had a statistically significant benefit when compared with a control (sterile water) on gastric emptying times and stool frequency over a 48-hour period

    • clinical or patient outcomes, such as effect on tolerance of enteral feeds, survival or nutritional status, were not evaluated.

Safety

  • Domperidone has been associated with adverse cardiac effects, including QT prolongation and arrhythmias.

  • The European Medicines Agency is currently reviewing the benefit–risk balance of domperidone-containing medicines.

Patient factors

  • Assessment of tolerability is difficult from the study assessed as only 22 neonates were included.

  • Summary of Product Characteristics recommends that the dose (for its licensed indications) should be determined accurately and followed strictly in neonates, infants, toddlers and small children.

Resource implications

  • Domperidone is available in various formulations with costs ranging from £1.14 for a 30-pack of 10 mg tablets to £12.53 for 200 ml of 1 mg/ml oral suspension.

Key points

Domperidone 1 mg/ml oral suspension, 30 mg suppositories and some brands of 10 mg tablets are licensed for relieving symptoms of nausea and vomiting in children. None of the formulations are licensed for stimulating gastrointestinal motility to promote tolerance of enteral feeds in any age group, so use for this indication is off-label.

  • There is very limited published evidence on using domperidone in children and young people for this specific off-label indication. Just 1 relevant study, a small (n=22) partially blinded, randomised crossover study, was found that included an enterally fed neonatal population (Gounaris et al. 2010). No further studies were found that used domperidone to stimulate gastrointestinal motility to promote tolerance of enteral feeds in children and young people.

The study investigated using domperidone oral solution to improve gastric emptying in enterally fed very low birth weight preterm neonates in an intensive care setting.

All neonates received 200 ml/kg/day of milk by nasogastric tube and were also randomised to receive either domperidone oral solution (0.3 mg/kg/8 hours) or a control treatment (an equivalent quantity of sterile water) for a 48-hour treatment period.

The study found that neonates had shorter mean gastric emptying times when receiving domperidone (47.6 minutes, standard deviation [SD] 23.9 minutes) compared with sterile water (68.2 minutes, SD 25.5 minutes) and this difference was statistically significant (p=0.008). Stool frequency was also statistically significantly increased using domperidone compared with water (mean number of stools passed in 48 hours: 2.4 compared with 1.8, p=0.038). Frequency of vomiting was reported as being similar in both groups.

The clinical and patient impact of these gastric motility improvements in terms of improving enteral feeding tolerance and the ability to maintain adequate nutrition was not directly measured and so is unclear.

The reliability and generalisability of the evidence from this single study is very limited because of its small sample size, short treatment duration and narrowly defined neonate population. The results are not generalisable to non-neonate populations including older children and young people.

The study was too small and short term to assess side effects or safety reliably.

The summaries of product characteristics for licensed domperidone products carry the precaution that the drug may be associated with an increased risk of serious ventricular arrhythmias (very rare, frequency of less than 1 in 10,000), QTc interval prolongation (an alteration of the electrical activity in the heart; frequency unknown) or sudden cardiac death (frequency unknown). Domperidone should therefore be used with caution in people who have existing prolongation of cardiac conduction intervals, particularly QTc, and in people with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart failure. Use of the lowest effective dose of domperidone is recommended in adults and children and use in combination with potent CYP3A4 inhibitors that prolong the QTc interval (for example, ketoconazole or erythromycin) should be avoided.

On 7 March 2013, the European Medicines Agency started a safety review of domperidone-containing medicines in relation to continued concerns about its adverse effects on the heart. No expected date for the final decision has been given.

Update

The following information has become available since this ESUOM was produced:

January 2015: NICE guideline on gastro-oesophageal reflux disease: recognition, diagnosis and management in children and young people published.

This guidance was mentioned in this evidence summary when it was first published as being in development. The NICE guideline on gastro-oesophageal reflux disease: recognition, diagnosis and management in children and young people has now been published. It recommends that healthcare professionals should not offer metoclopramide, domperidone or erythromycin to treat gastro-oesophageal reflux or gastro-oesophageal reflux disease without seeking specialist advice and taking into account their potential to cause adverse events. See the NICE guideline for more information.

30 September 2014: Domperidone: risks of cardiac side effects - indication restricted to nausea and vomiting, new contraindications, and reduced dose and duration of use.

A European review has confirmed that domperidone is associated with a small increased risk of serious cardiac side effects. Its use is now restricted to the relief of nausea and vomiting and the dosage and duration of use have been reduced. It should no longer be used for the treatment of bloating and heartburn. Domperidone is now contraindicated in those with underlying cardiac conditions and other risk factors. See the Medicines and Healthcare Products Regulatory Agency Drug Safety Update May 2014 for more information.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.