Prescribing Guidelines for Domperidone

(Includes risk of cardiac side effects – restricted indication, new contraindications, reduced dose & duration of use).

A European review assessed the benefits and risks of domperidone following continued reports of cardiac side effects. The review confirmed a small increased risk of serious cardiac side effects. A higher risk was observed in:

 Those over the age of 60 years  People taking daily oral domperidone doses of more than 30mg  Those taking QT-prolonging medicines or CYP3A4 inhibitors at the same time as domperidone.

For indications other than nausea and vomiting, the benefits were not considered to outweigh the cardiac risk. Based on these results of this review, the MHRA issued revised advice in April 2014 on the use of domperidone. Domperidone is restricted to the relief of symptoms of nausea and vomiting and the dosage and duration of use have also been reduced.

Domperidone is now contraindicated in those:  with conditions where cardiac conduction is, or could be, impaired.  with underlying cardiac diseases such as congestive heart failure.  receiving other medications known to prolong QT or potent CYP3A4 inhibitors.  with severe hepatic impairment.

Patients with these conditions should have their treatment reviewed at their next routine appointment and be switched to an alternative treatment if required.

Oral liquid formulations of domperidone should only be given via an appropriately designed, graduated oral syringe to ensure dose accuracy.

Recommended dose:

 Adults and adolescents over 12 years of age and weighing ≥35kg, the recommended maximum dose in 24 hours is 30mg (dose interval: 10mg up to three times daily).

(Maximum treatment duration should not exceed one week)

 Domperidone is no longer licensed for use in children younger than 12 years or those weighing less than 35 kg (MHRA December 2019).

Patients currently receiving long-term treatment with domperidone should be reassessed at a routine appointment to advise on treatment continuation, dose change, or cessation.

Advice to give to patients

 Domperidone should only be used for short periods of time to treat nausea and vomiting.  Talk to a doctor straight away if you experience dizziness; fainting; chest pain; or a rapid, fluttering, or pounding heartbeat while taking domperidone.

Availability of domperidone

Domperidone is no longer available without prescription. People now need to have a medical assessment before taking domperidone to

determine if it is suitable for them due to the risk of cardiac side effects.

Produced by West Essex CCG Medicines Optimisation Team August 2014; Updated and Approved MOPB September 2019; Updated and Approved MOPB January 2020 following MHRA Safety update.

Clinical use of domperidone across indications following the MHRA advice UKMI Summary: current position and available advice on the use of domperidone (May 2014)

Domperidone is used for a number of unlicensed and other indications not covered directly by the MHRA’s advice. Patients for whom domperidone might be considered currently include:

1. Adults with gastro-oesophageal reflux disease, dyspepsia, or gastroparesis 2. Adults receiving chemotherapy, for the prevention of nausea and vomiting 3. Children with gastro-oesophageal reflux disease 4. Breast feeding women where domperidone is used to stimulate milk production (i.e. as a galactogogue)

A number of publications have now been produced to help guide recommendations and prescribing in these areas.

1. Adults with gastro-oesophageal reflux disease, dyspepsia, or gastroparesis

A UKMi rapid communication produced in May 2014 summarised potential options for these indications. It suggests:  Reviews for all patients receiving long-term domperidone should be undertaken with a view to undertaking a trial withdrawal in conjunction with optimising other treatment options for GORD and dyspepsia.  For patients with gastroporesis, ‘on-demand’ domperidone (i.e. up to 10mg three times daily for up to 1 week) continues to be an option mindful of the revised contraindications.

2. Adults receiving chemotherapy, for the prevention of nausea and vomiting

As prescribing here involves higher (unlicensed) doses of domperidone, our advice would be that this is outside the expertise of a GP; therefore the prescribing and clinical responsibility, in this case should remain with the specialist.

3. Children with gastro-oesophageal reflux disease

The Neonatal and Paediatric Pharmacists’ Group produced advice on the use of domperidone in infants and children (May 2015). It discusses a variety of courses of action dependent on whether treatment is established or being considered, and whether congenital heart disease is present.  Consider reviewing children with established GORD who are already taking domperidone. In general, as stated by the MHRA advice, domperidone should only be used for the relief of the symptoms of nausea and vomiting  In patients who are newly diagnosed with GORD, follow the NICE NG1 guidance (January 2015) for the initial and pharmacological management of GORD.  Domperidone should only be prescribed for children by a specialist, and only if the benefits of using domperidone to treat GORD outweigh the risks of the cardiac adverse events (MOPB September 2019).

Medicines for Children have a leaflet for parents and carers entitled Domperidone for gastro-oesophageal reflux.

4. Use in nursing mothers to promote lactation (i.e. use as a galactogogue)

UKMI: Drug treatment of inadequate lactation (October 2014)  A health professional should always be involved in the decision to use a galactagogue.  Drugs to manage inadequate lactation should only be used where there is objective evidence to support diagnosis and where non- drug methods have failed.  There are no drugs licensed in the UK to improve lactation.  As long as the possible cardiac effects are taken into account, domperidone is considered to be the agent of choice for inadequate lactation because of its superior side effect profile, efficacy, and minimal passage into breast milk.  Domperidone should not be used for inadequate lactation where the mother or infant has a cardiac disorder or are receiving treatment with drugs known to affect the QT interval e.g. ketoconazole or erythromycin, in which case metoclopramide is preferred.  A maternal daily dose of 30mg domperidone should not be exceeded. The maximum treatment duration should not usually exceed one week.

References 1. European Medicines Agency Statement Domperidone-containing medicines (April 2014) 2. MHRA Domperidone: risks of cardiac side effects (May 2014) 3. MHRA Domperidone: small risk of heart problems (May 2014) Information for patients 4. MHRA Domperidone: no longer available without prescription (September 2014) 5. UKMI Summary: current position and available advice on the use of domperidone (May 2014) 6. UKMI Domperidone: new restrictions in use (May 2014) 7. UKMI Medicines Q&As Drug treatment of inadequate lactation (October 2014) 8. MHRA Domperidone for nausea and vomiting: lack of efficacy in children; reminder of contraindications in adults and adolescents (December 2019)

Produced by West Essex CCG Medicines Optimisation Team August 2014; Updated and Approved MOPB September 2019; Updated and Approved MOPB January 2020 following MHRA Safety update.