An examination appearing in PLOS One of an unpublished study from 2009 suggested that information the FDA used to approve doxylamine-pyridoxine for treatment of nausea and vomiting in pregnant women showed the drug was not effective.
The drug is included in the American College of Obstetricians and Gynecologists’ (ACOG) guidelines as the first-line pharmacological therapies for nausea and vomiting for women who are pregnant.
“Pregnant women should be given accurate information about this and other treatments,” Navindra Persaud, MD, department of family and community medicine, St. Michael’s Hospital in Toronto, told Healio Family Medicine. “Unfortunately, this information [regarding doxylamine-pyridoxine] has not been available to women taking the medication.”
In the DIC-301 trial from 2009, the efficacy of both doxylamine 10 mg and pyridoxine 10 mg taken from two to four times per day vs. placebo in the treatment of nausea and vomiting was assessed in 280 pregnant women matched in a 1:1 ratio. Information from 131 active treatment participants and 125 control participants were analyzed. By study’s end, 101 active treatment participants and 86 control participants provided primary outcome measures. Symptoms were scored by utilizing the 13-point pregnancy unique quantification of emesis scale between baseline and 14 days using an ANCOVA.
Using previously unpublished data obtained from public trial registration information, FDA review documents and study report documents from Health Canada, Persaud and colleagues re-analyzed the data from this study to address differences in prior reports of the trial. They found that there was a 0.73 point improvement (95% CI, 0.21-1.25) in symptoms scores with doxylamine-pyridoxine vs. placebo “when last observation carried forward imputation was used for missing data.” However, they added that this difference was not statistically significant when using different approaches to address the missing data (eg, 0.38; 95% CI, –0.08 to 0.84 using complete data).
Persaud and colleagues also reported that symptom scores plateau after day 10 and “improved substantially” during the 2-week trial in both groups; however, the difference between groups also decreased after the 10th day.
“Both of these findings could be explained by the natural history of the condition, that is, by the resolution of symptoms irrespective of treatment. This natural resolution could account for the lack of clinical important difference between groups,” Persaud and colleagues wrote.
According to Persaud, doxylamine-pyridoxine is still a popular option for pregnant women and approved for use in the U.S. and Canada. He told Healio Family Medicine that four prescriptions for the medication were filled for every five live births in Canada in 2014.