Summary: current position and available
advice on the use of domperidone
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Pharmacovigilance Risk Assessment Committee (PRAC) of published and unpublished data2.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 recommended domperidone be restricted to a maximum dose of 10mg up to three
times daily for a general indication of nausea and vomiting in adults 1. Overall, the benefit to
risk was considered to be positive for other indications. It was also considered that wellestablished paediatric use should continue, but recommended 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, two focussed 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 indication 3, 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probably based primarily on unpublished data.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 MHRA advice
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:
1.
2.
3.
4.
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.
1. Adults with gastro-oesophageal reflux disease, dyspepsia, or gastroparesis
A UKMi 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
2. 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).
3. Children with gastro-oesophageal reflux disease
The Neonatal and Paediatric Pharmacists’ Group have produced interim advice on
domperidone use in children.
It discusses a variety of courses of action dependent on whether treatment is established or
being considered, and whether congenital heart disease is present.
4. Use in nursing mothers to promote lactation (i.e. use as a galactogogue)
A UKMi rapid communication recommends continued use of domperidone, albeit at a reduced
dose and duration, and only once all other options have been exhausted.
Ben Rehman
b.rehman@nhs.net