Summary Safety Review - Domperidone - Assessing the Potential Risk of Psychiatric Withdrawal Events when Used for Lactation Stimulation

Domperidone-containing products

Psychiatric withdrawal events including, but not limited to, depression, anxiety and insomnia following sudden discontinuation or tapering (dose reduction) of domperidone used to stimulate lactation

• Domperidone is authorized for sale in Canada to treat symptoms of slowed stomach emptying seen with certain gastrointestinal conditions, and to prevent symptoms, such as nausea and vomiting, caused by some drugs used to treat Parkinson’s disease.

• Domperidone is not authorized in Canada to promote lactation, but data derived from Canadian sources indicate that it has been prescribed for this off-label (not authorized) use^1,2.

• Health Canada reviewed the potential risk of psychiatric withdrawal events following sudden discontinuation or tapering of domperidone used for lactation stimulation. The safety review was triggered by reports published in the scientific literature concerning this risk and the off-label use of domperidone for lactation stimulation.

• Health Canada’s review of the available information found a link between the sudden discontinuation or tapering of domperidone, used off-label for lactation stimulation, and the risk of psychiatric withdrawal events. This link was mostly observed in patients taking daily doses greater than the maximum recommended dose of 30 mg per day. However, the review was limited by the small number of cases.

• Health Canada will work with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for domperidone-containing products to note that cases of psychiatric withdrawal events have been reported. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

Health Canada reviewed the potential risk of psychiatric withdrawal events following sudden discontinuation or tapering of domperidone used to stimulate lactation. The safety review was triggered by reports published in the scientific literature concerning this risk and the off-label use of domperidone for lactation stimulation.

Domperidone is not authorized in Canada to promote lactation, but data derived from Canadian sources indicate that it has been prescribed for this off-label use^1,2. Daily doses exceeding 30 mg have been reported in the literature for this off-label use.

• Domperidone is a prescription drug authorized for sale in Canada to treat symptoms of slowed stomach emptying seen with certain gastrointestinal disorders, and to prevent symptoms, such as nausea and vomiting, caused by some drugs used to treat Parkinson’s disease. The maximum recommended daily dose of domperidone for all authorized uses in Canada is 30 mg.

• Domperidone has been marketed in Canada since 1985. It is currently available in 10 mg tablets. Various generic domperidone products are available in Canada.

• Approximately 1.7 million prescriptions were filled for domperidone in 2021 across all indications (authorized and not authorized uses).

• Health Canada reviewed the available information from searches of the Canada Vigilance Database^a and the published literature.

• Health Canada reviewed 9 cases (4 Canadian and 5 international) of psychiatric withdrawal events following sudden discontinuation or tapering of domperidone when used for lactation stimulation. Of the 9 cases, 7 (4 Canadian) were found to be probably linked to the use of domperidone and 2 were found to be possibly linked. The total daily dose of domperidone used in 8 of the 9 cases was reported to be higher than 30 mg. In all cases, the duration of domperidone use prior to the initial discontinuation or tapering attempt was longer than 4 weeks.

• Health Canada also reviewed articles published in the scientific literature, which identified potential biological mechanisms that may explain how sudden discontinuation or tapering of domperidone, when used to stimulate lactation, could lead to psychiatric withdrawal events.

• Health Canada’s review of the available information found a link between the sudden discontinuation or tapering of domperidone, used off-label for lactation stimulation, and the risk of psychiatric withdrawal events. This link was mostly observed in patients taking daily doses greater than the maximum recommended dose of 30 mg per day. However, the review was limited by the small number of cases.

• Health Canada will work with the manufacturers to update the CPM for domperidone-containing products to note that cases of psychiatric withdrawal events have been reported.

• Health Canada will also inform healthcare professionals about this update through a Health Product Infowatch communication.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of domperidone and other health products to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving domperidone, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of domperidone both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

1. Moriello, C., Paterson, J. M., Reynier, P., Dahl, M., Aibibula, W., Fisher, A., Gamble, J. M., Kuo, I. F., Ronksley, P. E., Winquist, B., Filion, K. B., & Canadian Network for Observational Drug Effect Studies (CNODES) Investigators (2021). Off-label postpartum use of domperidone in Canada: a multidatabase cohort study. CMAJ open, 9(2), E500–E509. https://doi.org/10.9778/cmajo.20200084

2. Smolina, K., Morgan, S. G., Hanley, G. E., Oberlander, T. F., & Mintzes, B. (2016). Postpartum domperidone use in British Columbia: a retrospective cohort study. CMAJ open, 4(1), E13–E19. https://doi.org/10.9778/cmajo.20150067

1. Canadian reports can be accessed through the Canada Vigilance Online Database.