TORONTO — A medication commonly prescribed for morning sickness during pregnancy appears to be ineffective, based on results from a previously unpublished clinical trial paid for by its Canadian manufacturer and submitted as part of the approval process to both Health Canada and the FDA, a new report suggests.
Dr. Nav Persaud, a family physician and researcher at St. Michael's Hospital in Toronto, obtained thousands of pages of documents from Health Canada related to the 2010 clinical study, which suggested Diclectin (pyridoxine-doxylamine) was effective in reducing nausea and vomiting in pregnant women.
The trial sponsored by drug-maker Duchesnay Inc. of Quebec was conducted at six U.S. medical centres and compared symptom reduction in 101 women put on the medication versus 86 women given a placebo, or dummy pill.
At the end of the two-week study, there was little difference in symptoms between the two groups; on a 13-point scale, women who took the drug reported symptom reduction only 0.7 points higher than that for women who got a placebo, the documents show.
The study specified that the findings would be clinically important only if there were a three-point reduction in symptoms, Persaud said Wednesday in an interview. "But on all counts, there was less than one point between the groups."
The analysis by Persaud and colleagues was published online Wednesday in the journal PLOS ONE.
Diclectin, sold as Diclegis in the U.S., is prescribed for alleviating morning sickness to millions of women around the world, including tens of thousands each year in Canada. At least one prescription for the drug is filled for every two births in this country.
Persaud once routinely prescribed the medication, which is recommended by the Society for Obstetricians and Gynecology of Canada (SOGC). But in 2011, one of his patients questioned use of the drug, prompting him to start investigating the safety and effectiveness profile that led to the drug being granted marketing approval.
"It did take a long time to get the information, but after looking at it, my practice has completely changed," said Persaud, who suggests that Health Canada and the U.S. Food and Drug Administration should rethink their endorsement of the medication.
Diclectin comes in a time-released pill that contains two main ingredients: pyridoxine, or vitamin B6, and doxylamine, an antihistamine.
A Health Canada spokesperson said the federal department reviewed the safety and effectiveness data for Diclectin in 2016, including seeking advice from an external expert panel.
"No new safety or efficacy issues were identified as part of the review," the spokesperson said by email. "The available evidence continues to support Diclectin in the treatment of nausea and vomiting during pregnancy."
As well, updated SOGC guidelines continue to recommend pyridoxine alone or doxylamine/pyridoxine combination therapy (Diclectin) as a first-line treatment for nausea and vomiting in pregnancy "when conservative measures have not been effective," the spokesperson said.
"Diclectin has been prescribed for more than 40 years in Canada and has been repeatedly proven safe and effective for use throughout pregnancy," said Duchesnay spokeswoman Fiona Story.
Both the safety and efficacy of doxylamine-pyridoxine have been proven in multiple studies and an estimated 35 million pregnant women worldwide have used the drug to manage their symptoms, Story said by email.
The medication has been endorsed as a first-line therapy for morning sickness in guidelines issued by professional medical organizations like the SOGC and approved by regulatory bodies in countries around the globe, she said.
"It is important to note that the specific clinical trial (DIC-301) being referenced ... was designed and developed in collaboration with the FDA through a special protocol assessment. The clinical trial achieved a statistically significant endpoint using the method of analysis requested by the FDA in accordance with all FDA requirements."
Still, pregnant women with nausea and vomiting may want to consider other treatment options, said Persaud, referring specifically to the more common form of morning sickness, not the severe type known as hyperemesis gravidarum that has repeatedly hospitalized the Duchess of Cambridge.
"I have completely stopped prescribing the medication and I would recommend that women with nausea and vomiting during pregnancy see their health-care provider about effective treatments," he said.
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