Summary: current position and available advice on the use ofdomperidone
May 2014
Background and regulatory position
The MHRA issued revised advice in April on the use of domperidone following a European wide review of its safety1. The advice was based on an assessment by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) of published and unpublished data2.
The MHRA recommendeddomperidonebe restricted to a maximum dose of 10mg up to three times daily for a general indication of nausea and vomiting in adults1. Overall, the benefit to risk was considered to be positive for other indications. It was also considered that well-established paediatric use should continue, butrecommended dose reductions1. Unlicensed indications were not considered as part of the assessment process, although it is suggested that the principles underpinning the MHRA recommendations are applied when considering unlicensed (off-label) use1, 2. In addition, domperidone is now contraindicated for patients with a broad range of cardiac conduction and associated conditions, as well as for patients taking a range of QT prolonging or CYP3A4 inhibiting medicines. It should be used with particular caution in those over 60 years of age1, 2.
The basis of the PRAC assessment and the subsequent MHRA advice is not entirely clear as the primary data underpinning the advice has not been made fully available. From the published literature, four epidemiological studies have been identified all of which were published prior to previous European advice in 20113-6. Of these studies, twofocussed on the relationship between domperidone and cardiac outcomes (as opposed to the broader considerations of drugs prolonging the QT interval)3, 5. The studies do not determine equivocally the relationship between domperidone dose and cardiac risk; they were not free of potential confounders; and they did not consider risk on the basis of indication3, 5. Given the timing of the publications and the study limitations, the PRAC’s 2014 assessment is probably based primarily on unpublished data. Without access to these data it is difficult to independently assess the extent to which the benefit to risk is affected across a range of indications. However It is important to consider the revised MHRA advice when considering the use of domperidone in practice.
Clinical use of domperidone across indications following the MHRAadvice
Domperidone is used for a variety of unlicensed and other indications not covered directly by the MHRA’s advice.
Patients for whom domperidone might be considered currently include:
- Adults with gastro-oesophageal reflux disease, dyspepsia, or gastroparesis
- Adults receiving chemotherapy, for the prevention of nausea and vomiting
- Children with gastro-oesophageal reflux disease
- 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.
- Adults with gastro-oesophageal reflux disease, dyspepsia, or gastroparesis
AUKMi rapid communication 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
- Adults receiving chemotherapy, for the prevention of nausea and vomiting
A rapid review for the London Cancer New Drugs Group presents various options, ranging from non-adoption of the MHRA recommendations (continuing higher domperidone doses), through dose restriction, to a wholesale switch to alternative antiemetic protocols (although use of these, which include 5-HT3 antagonists and other options, have their own safety and financial implications).
- Children with gastro-oesophageal reflux disease
The Neonatal and Paediatric Pharmacists’ Group have produced interim advice on domperidone use in children.
Itdiscusses a variety of courses of action dependent on whether treatment is established or being considered, and whether congenital heart disease is present.
- Use in nursing mothers to promote lactation (i.e. use as a galactogogue)
AUKMi rapid communicationrecommends continued use of domperidone, albeit at a reduced dose and duration, and only once all other options have been exhausted.
Ben Rehman