Advice

Overview for healthcare professionals

Overview for healthcare professionals

Domperidone is a dopamine receptor antagonist that is used to relieve symptoms of nausea and vomiting in adults and children. It is also used to relieve symptoms of indigestion or feelings of discomfort or fullness in the stomach in adults.

Regulatory status of domperidone

Domperidone 10 mg tablets, 1 mg/ml oral suspension and 30 mg suppositories are licensed in the UK for relieving symptoms of nausea and vomiting, epigastric sense of fullness, upper abdominal discomfort and regurgitation of gastric contents in adults. In children, 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. None of the formulations (tablets, oral suspension or suppositories) are licensed for stimulating gastrointestinal motility to promote tolerance of enteral feeds in any age group, so use for this indication is off-label. The oral suspension is the most likely formulation to be used off-label for this indication in infants because of its acceptability to infants and because it allows the smaller doses that are likely to be needed in younger children to be administered more accurately.

In line with the guidance from the General Medical Council (GMC), it is the responsibility of the prescriber to determine the clinical need of the patient and the suitability of using domperidone outside its authorised indications.

Evidence statements

  • One small (n=22) and short-term, partially blinded, randomised crossover study (Gounaris et al. 2010) found that giving domperidone oral solution 0.3 mg/kg/8 hours over 48 hours led to a statistically significant improvement in gastric emptying time compared with a control (sterile water) in preterm, very low birth weight neonates being enterally fed in an intensive care unit.

  • The number of stools passed also statistically significantly increased when using domperidone compared with water, but frequency of vomiting was described as similar in both groups.

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

  • The small sample size, narrow study population and short treatment duration in this study severely limit its ability to reliably assess whether domperidone is effective at promoting tolerance of enteral feeds in the study population as well as in wider populations of children and young people, or for longer periods of time.

  • Although the authors report that no side effects were experienced by neonates in the study, reliable evidence of the safety of domperidone cannot be established because of the short-term nature of the treatment period.

  • No further studies were found that used domperidone to stimulate gastrointestinal motility to promote tolerance of enteral feeds in children and young people.

  • On 7 March 2013, the European Medicines Agency started a new 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.

Summary of the evidence

This section gives a brief summary of the main evidence. A more thorough analysis is given in the Evidence review section.

Domperidone 10 mg tablets, 1 mg/ml oral suspension and 30 mg suppositories are licensed in the UK for the relief of symptoms of nausea and vomiting, epigastric sense of fullness, upper abdominal discomfort and regurgitation of gastric contents in adults. In children domperidone 1 mg/ml oral suspension, 30 mg suppositories and some brands of 10 mg tablets are licensed for the relief of symptoms of nausea and vomiting. There are currently no UK treatments licensed for children and young people (under 18) to promote tolerance of enteral feeds. Consequently, using domperidone to promote tolerance of enteral feeds in this group represents off-label use.

Efficacy

There was very limited directly applicable research relevant to this specific off-label use of domperidone. For important evidence selection information, see the Evidence selection section.

The only relevant published information found came from a single non-UK-based study (Gounaris et al. 2010). This was a small (n=22), randomised, crossover study involving enterally fed very low birth weight preterm neonates with a clinical history of problems with gut motility in an intensive care setting. The authors describe the study as partially blinded, but it is not clear who was blind to treatments other than the radiologists involved in taking measurements of gastric emptying times in the neonates.

The study was small and short term, so cannot provide reliable or generalisable information on the effectiveness or safety of domperidone in children and young people for this off-label use.

In the single study identified (Gounaris et al. 2010), all very low birth weight preterm neonates were given 200 ml/kg/day of milk (either standard premature infant formula [n=12] or their mother's own supplemented milk [n=10]) by nasogastric tube. In addition, they received 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 primary outcome was change in gastric emptying time. Secondary outcomes included the number of stool passages in both groups and the differences in gastric emptying between neonates fed with formula milk and those fed with their mother's own supplemented milk.

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. No further clinical or patient outcomes of feeding tolerance were recorded, such as nutrient absorption, or the impact on growth or survival.

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 typical cost of using off-label domperidone to promote tolerance of enteral feeds and to stimulate gut motility could not be established because of lack of information on typical off-label dosing and treatment duration.

Table 1 Summary of the crossover study: Gounaris et al. (2010)

Domperidone

(0.3 mg/kg/8 hours over 48 hours)

Sterile water

(same quantity as domperidone over 48 hours)

Analysis

Randomiseda

n=22

n=22

All 22 participants completed the trial and were included in the analysis

Efficacy

Primary outcome: gastric emptying, ultrasound measurement of ACSA (mean half-value time, minutes)

47.6

(SD 23.9)

68.2

(SD 25.5)

p=0.008

Absolute difference=20.6 minutes after the 48-hour treatment period

Secondary outcome: mean number of stools passed during 48-hour treatment period

2.4

(SD 1.9)

1.8

(SD 0.7)

p=0.038

Absolute difference=0.6 stools during the 48-hour treatment period

Other outcomes:

Number of times vomiting occurred

Not reported

Not reported

The publication reported no difference between groups in the number of times vomiting occurred

Gastric residual

Not reported

Not reported

Abdominal distension

Not reported

Not reported

Safety

Adverse events

Not reported

Not reported

The publication reported there were 'no adverse effects'

Abbreviations: ACSA, antral cross-sectional area; n, number of patients; SD, standard deviation.

a The study was a crossover design, so all neonates received both treatments with treatment order determined by randomisation. All neonates were on full enteral feeding during study treatment and received 200 ml/kg/day of milk by nasogastric tube given by gravity.

Safety

The study was too small and too short for side-effect frequencies or safety to be assessed reliably.

The summaries of product characteristics for licensed domperidone products contain the precaution that epidemiological studies have shown that domperidone 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). They specify that domperidone should 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. They also recommend that domperidone should be used at the lowest effective dose in adults and children and that using it in combination with potent CYP3A4 inhibitors that prolong the QTc interval 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. The European Medicines Agency will review all available data on the benefit–risk balance of domperidone-containing medicines, and issue an opinion on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the European Union. No expected date for the final decision has been given.

Cost effectiveness and cost

No information on the typical dose or treatment duration of off-label domperidone to promote tolerance of enteral feeds in children and young people was available at the time this evidence summary was prepared. Therefore, it was not possible to estimate daily, weekly or monthly costs with any degree of certainty.

The NHS Electronic Drug Tariff (July 2013) lists the price for domperidone formulations as follows:

  • Domperidone 10 mg tablet, 30-tablet pack: £1.14

  • Domperidone 10 mg tablet, 100-tablet pack: £3.80

  • Domperidone 30 mg suppositories, 10-suppository pack: £3.06

  • Domperidone 1 mg/ml oral suspension sugar free, 200 ml pack: £12.53