This week, Health Canada publicly confirmed that it is reviewing the safety of domperidone, a drug used to treat gastrointestinal symptoms that has also been prescribed off-label to improve breast milk supply.

Here's a look at key properties of the drug and what the issues are with it:

How does domperidone work?

Domperidone blocks some of the body's dopamine receptors, called D2 receptors. Dopamine is a neurotransmitter, but it's not just found in the brain. There are also D2 dopamine receptors in the smooth muscle of the gastrointestinal tract, When domperidone blocks those receptors, it causes increased movement through the digestive system, relieving some gastrointestinal symptoms and treating nausea.

That's what the drug is approved by Health Canada to do.

But a side-effect of taking domperidone can be increased breast milk production. There are also D2 dopamine receptors in the pituitary gland, which produces a hormone called prolactin that stimulates lactation. When the receptors are blocked, more prolactin is secreted, which in turn increases breast milk.

Health Canada never approved domperidone for use in lactation, but is aware that many doctors and midwives have prescribed it for that purpose — that's called prescribing a drug "off-label."


How long has domperidone been around?

According to Health Canada, domperidone has been marketed in Canada since 1985 for managing symptoms of gastrointestinal disorders.

When did health-care providers start prescribing it to increase breastmilk?

Dr. Jack Newman, a pediatrician who has long been recognized as an expert on breastfeeding, told The Canadian Press that he's been prescribing domperidone for lactation since the 1980s.

It's not clear when it became more widely prescribed, but studies published in the Canadian Medical Association Journal (CMAJ) suggest the use of the drug to help breastfeeding increased from the early 2000s through 2017.


How effective is it?

Not all pediatricians agree on how effective domperidone is at increasing breastmilk.

"We initially thought it was going to be this magic pill, but it really hasn't proven to be that way," said Dr. Maya Bunik, a professor of pediatrics at Children's Hospital Colorado and chair of the American Academy of Pediatrics breastfeeding section.

There aren't enough rigorous studies "to tell whether it really has any effect or not," she said.

But Newman, who is the founder of the International Breastfeeding Centre based in Toronto, said after working with thousands of breastfeeding mothers for more than three decades, "there's no question" that domperidone works.

However, he said, if new mothers had enough support to help them breastfeed as soon as their babies were born, he wouldn't need to prescribe the medication.

"If mothers got a good start in hospital with breastfeeding, then we would be using a lot less domperidone," Newman said.

Suzanne Campbell, a nursing professor specializing in breastfeeding at the University of British Columbia, said it's possible that there's a psychological component to taking domperidone, because knowing the drug has worked for others helps the mother relax and have new confidence in her ability to breastfeed.

"Psychologically, if the mother is so stressed and anxious, that's cutting off the feedback loops that not only make the milk but help to release the milk," she said.


Why is Health Canada doing a safety review?

Health Canada says it started a safety review in December because of "domestic and foreign case reports of withdrawal symptoms after stopping or reducing the dose of domperidone used to stimulate lactation."

Health Canada didn't specify which case reports it's reviewing, but researchers at the University of British Columbia (UBC) and at the InfantRisk Center at Texas Tech University Health Sciences Center have documented cases of women who suffered severe anxiety, depression, intrusive disturbing thoughts and insomnia while trying to stop taking domperidone.

Newman says that his clinic gives patients clear instructions on how to wean off the drug slowly to prevent withdrawal symptoms and that anyone else who prescribes domperidone should be doing the same.

Alixandra Bacon, president of the Canadian Association of Midwives, said recent media coverage about the drug has led to some clients to panic and "quit their domperidone cold turkey."

"The biggest risk for these rare but possible mental-health side-effects is not weaning off the medication properly," she said.

Bacon urged breastfeeding women to "engage with your health-care provider" if they have concerns.

Why would withdrawal symptoms happen with domperidone?

"The bottom line is we don't know," said Dr. Jonathan Zipursky, a specialist in clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre in Toronto.

In general, domperidone doesn't cross the blood-brain barrier, or only crosses in small amounts.

Researchers have different theories, he said. One is that higher concentrations of the drug get into the brain in some people but not others — and that could explain why only some breastfeeding mothers experience withdrawal symptoms.

Another possible theory is that because prolactin is a hormone, the decreased levels when someone stops taking domperidone could trigger the symptoms.


Are there other safety concerns about domperidone?


Health Canada has previously issued warnings about potential cardiac risks associated with domperidone.

In Canada, the product's labelling includes a maximum recommended daily dose of 30 mg. Much higher doses, generally starting at 90 mg a day, are prescribed to promote lactation.

The FDA has banned domperidone altogether in the U.S — even for its intended use to treat gastrointestinal symptoms — because of concerns about cardiac risks.

"(With) these really high doses that have not been studied, you know, the cardiac adverse effects are something that I really worry about," said Kaytlin Krutsch, a pharmacotherapy specialist at the InfantRisk Center at Texas Tech University Health Sciences Center.

"The psychiatric ones I worry about too. But I think that probably the cardiac ones are more common. We don't know how common the psychiatric ones are," she said.

In a domperidone information page on the International Breastfeeding Centre website, Newman argues the heart-related side-effects happened when "very sick patients" were given domperidone intravenously and to people over age 70, "many of whom had pre-existing health conditions."

The webpage also says the clinic is not aware of anyone it has treated with domperidone experiencing heart-related side-effects.

This report by The Canadian Press was first published Feb. 3, 2023.