Health Canada reviewing safety of controversial breastfeeding drug
Review follows CBC investigation into withdrawal effects from domperidone
Health Canada has launched a safety review of the psychological withdrawal symptoms associated with stopping or reducing use of a drug commonly prescribed to help women breastfeed.
The agency confirmed the review in an email to CBC News.
"This safety review, which started in December 2022, was prompted by domestic and foreign case reports of withdrawal symptoms after stopping or reducing the dose of domperidone used to stimulate lactation," the statement said.
Domperidone is approved in Canada to treat gastrointestinal disorders. Health Canada has never authorized its use as a lactation aid, but it is widely prescribed off-label for this purpose.
The Health Canada review follows a CBC News investigation into severe psychological effects that can occur when some women stop taking the drug. Women who spoke to the CBC described anxiety, inability to sleep and thoughts of self-harm severe enough that in some cases they became incapable of caring for their children or returning to work. One woman described multiple attempts to take her own life.
CBC's investigation also found domperidone is prescribed by some doctors to stimulate lactation at doses three to five times higher than what is recommended by both Health Canada and the drug manufacturer. Because this is not an approved use or dosage anywhere in the world, there are no large-scale clinical trials that shed any light on how often these side effects occur.
This makes it challenging for regulators like Health Canada to evaluate the safety of a drug for an off-label purpose, said Mina Tadrous, an assistant professor at the Leslie Dan Faculty of Pharmacy at the University of Toronto who specializes in drug safety.
"The company may not have intended it for that, so the original clinical trials were not designed for that. And so it means that they have to look at different mechanisms to be able to evaluate the safety of these drugs," he said.
That can include looking at data from other countries with larger populations, according to Tadrous.
Case studies document concerns
There are, however, case studies documenting the withdrawal effects, including three published in November 2022 in the peer-reviewed journal Breastfeeding Medicine.
Domperidone blocks dopamine receptors in the brain, which stimulates the release of prolactin. This causes lactation, the authors note, but can also cause domperidone to act as an antipsychotic. The authors, from the Texas Tech University Health Sciences Center, also noted withdrawal symptoms are typically less severe when women taper off the drug slowly.
The most recent case studies are from the United States, where domperidone is not approved by the Food and Drug Administration (FDA) for any purpose. CBC's investigation found some American women get the drug from doctors in Canada.
Health Canada will review "all relevant domestic and foreign case reports," the statement said.
Reviews can result in Health Canada requesting more information, studies or monitoring by the manufacturer. They can also result in warnings to patients and health-care providers, changes to how a drug is labelled or, if necessary, the withdrawal of a drug from the market "if the benefits no longer outweigh the risks of the product," according to the statement released by the department.
"The decision to take action, including issuing a warning, is not based solely on the number of case reports, but on a comprehensive assessment of the information contained in these case reports," Health Canada's statement said.
"Should new safety risks be confirmed, Health Canada will take appropriate action and continue to keep Canadians informed."
The department expects the review will be completed by summer 2023.
WATCH | Women report alarming withdrawal effects after taking domperidone as a lactation aid:
The distinction between quantity and quality of reports is important, Tadrous said, because large numbers of reports, especially from non-clinicians, may only indicate people believe there's a connection between a drug and a reaction.
"That's the lesson we've learned with vaccines, for example, where these adverse-event systems are flooded," he said.
"And so if you base something just on the number of reports without doing a thorough investigation and a different type of study design that reduces bias … you might reach a false conclusion."
Health Canada has conducted multiple safety reviews of domperidone, most recently in 2021. Previous reviews confirmed the risk of serious abnormal heart rhythms and sudden cardiac death related to domperidone use. These reviews resulted in Health Canada introducing a maximum daily dose recommendation of 30 milligrams and restricting its use in patients with certain cardiac conditions or taking other drugs.
With files from Leah Hendry