Domperidone is a medication which is licenced for nausea and vomiting. In addition to the licenced indications, domperidone is also can be given to start or increase breast milk production following childbirth. However, this unlicenced indication of domperidone for breast milk production can be associated with side effects of depression, anxiety and insomnia. Currently, it is not known how much unlicenced use of domperidone there is in the UK. Therefore, the size of the population at risk of adverse reactions associated with the use of domperidone such as depression, anxiety and insomnia needs to be estimated.
The current study aims to quantify the use of domperidone in postpartum women, so the feasibility of a retrospective cohort study to describe the prescribing of domperidone to women postpartum can be concluded. The results of the cohort study will help us to identify the recording of prescriptions of unlicenced use of domperidone for starting or increasing breast milk production which will aid in our assessment of risks of adverse reactions. This will enable us to direct advice on the use of domperidone to those populations.
Domperidone is a dopamine receptor antagonist which stimulates peristalsis and is licenced for the treatment of nausea, vomiting and gastric pain. Domperidone also increases prolactin levels and therefore, in addition to licenced indications, is given off-label as a galactagogue. The off-label use of domperidone as a lactation stimulant is associated with an increased risk of depression, anxiety and insomnia. The extent of off-label use of domperidone is unknown but could be widespread. However, the identification of off-label use is challenging as it is not known what codes are used by GPs to record this usage. Therefore we aim to estimate the size of the population at risk of adverse reactions associated with the use of domperidone.
The feasibility study will quantify domperidone prescriptions in pregnant and postpartum women who are likely to be given the domperidone off-label. This study will use CPRD Aurum data to identify prescriptions of domperidone, and the Pregnancy Register data set will provide a study population. The null hypothesis is that the proportion of prescriptions before and after the delivery of a baby is the same. Any discrepancies in counts will be noted and the assumption that the prescription of domperidone after live birth until a baby is six months old is given off-label for lactation stimulation will be explored.
The analysis will quantify the number of domperidone prescriptions given between 2000 and 2023 to women who had a live birth, thus quantifying the prescribing of domperidone in a population of pregnant and postpartum women and comparing indications. The study findings will support the development of a list of codes to identify the off-label use of domperidone in a subsequent retrospective cohort study. The findings will aid in the planning of safety monitoring activities, including epidemiological studies to explore complications associated with off-label prescribing of domperidone.
The following outcome measures would be calculated from the Pregnancy Register data linked to CPRD Aurum data:
• The number (proportion) of women who received at least one prescription for domperidone during pregnancy or postpartum;
• The number of prescriptions per woman, start and duration of treatment.
• The list of indications of domperidone prescriptions will be described and their frequencies presented.
• Descriptive statistics will be conducted to quantify the number of prescriptions in different strata of the study population (e.g., during pregnancy and after delivery, by gestational age, postpartum period, and maternal age).
• Multiple pregnancies and prescriptions will be allowed per woman.
If the stratified analysis will result in small cell counts (<5 events per patient), for instance when the distribution of prescriptions is produced according to maternal age, the grouped age categories of maternal age will be produced to include a summary of cells with low counts. This will minimise the risk of inadvertently identifying patients or practices during the conduct or publication of the study.
Based on the outcome measures listed above, the feasibility of a retrospective cohort study will be concluded where comorbidity profile and concomitant therapy will be used to work out the indications for the use of domperidone.
Katherine Donegan - Chief Investigator - MHRA
Svetlana Buzdugan - Corresponding Applicant - MHRA
Svetlana Buzdugan - Collaborator - MHRA
CPRD Aurum Pregnancy Register