Doxylamine-Pyridoxine Combo Prevents Nausea in Pregnancy

SAN FRANCISCO, California — The doxylamine–pyridoxine combination might work best when it is administered before, instead of after, the symptoms of morning sickness begin, according to a new study.

"We may find that in the future this prevents maternal and fetal complications. It may reduce the need for enteral and parenteral therapy and their associated risks," said Caroline Maltepe, BA, from the Hospital for Sick Children in Toronto, Ontario, Canada, who presented the study results here at the Society for Maternal-Fetal Medicine 33rd Annual Meeting.

The researchers found a greater reduction in the recurrence of hyperemesis gravidarum in those who used the doxylamine–pyridoxine combination preemptively than in those who took the drug when symptoms began (43% vs 17%; P < .05).

The combination, marketed by Duchesnay as Diclectin, is a delayed-release formulation of doxylamine plus pyridoxine (vitamin B₆). The drug is widely used in Canada. It was previously available in the United States, as Bendectin, but was voluntarily removed from the market when lawsuits were filed alleging birth defects. A US Food and Drug Administration panel later concluded that no association between the drug and birth defects has been demonstrated.

The researchers, led by Gideon Koren, MD, director of the Motherisk Program at the Hospital for Sick Children, recruited 60 pregnant women with a history of severe nausea and vomiting during pregnancy or hyperemesis gravidarum. The women were part of Motherisk, a popular Toronto-based pregnancy helpline.

The participants reported how often they experienced nausea, vomiting, gagging, and retching and how well they slept in the previous 24 hours on a scale developed by the researchers. The acronym for the Pregnancy Unique Quantification of Emesis scoring system — PUQE — drew laughter from the audience during the presentation.

The women also rated their overall wellbeing.

PUQE Score

The researchers randomly assigned half the women to take the delayed-release formulation (doxylamine 10 mg plus pyridoxine 10 mg) before experiencing the symptoms of morning sickness and half to take it when they felt sick.

All women were instructed to start with 2 tablets a day and to increase the number of tablets as symptoms worsened. Four tablets per day is the standard dose.

The Motherisk helpline operators provided detailed counseling about diet and lifestyle to both groups of women. The 2 groups were similar in age, body mass index, and history of severe nausea and vomiting. The daily dose in both groups ranged from 2 to 9 tablets.

The researchers found that a PUQE score above 11 (meaning less moderate to severe nausea and vomiting) was less common in the preemptive group than in the group with symptoms (15% vs 39%; P < .04).

They also found that peak PUQE scores correlated negatively with wellbeing.

Study Under Fire

After the presentation, a member of the audience asked why the study did not include a placebo. Maltepe explained that "it wouldn't be ethical" to give these women placebo. The questioner shot back that "it's unethical to promote this industry-funded study based on this study design."

Another audience member asked if the Motherisk helpline receives funding from Duchesnay, the drug's manufacturer. "As well as Health Canada," Maltepe responded.

"And women are calling in and being directed to this product?" the questioner asked.

"No, our counseling is very extensive, as I mentioned," Maltepe said. "We explain all nonmedical approaches, we explain dietary and lifestyle strategies, and then we explain all medications. Diclectin is first-line in Canada, so yes, it will be explained, as well as many other antiemetic therapies."

Robert Silver, MD, professor of obstetrics and gynecology at the University of Utah in Salt Lake City, told Medscape Medical News that he considers this study "very flawed" because it did not include a placebo control.

He pointed out that many physicians currently prescribe a combination of doxylamine plus vitamin B₆ as prophylaxis in women with a history of severe morning sickness, but he added that there is no good evidence to show whether this approach is effective.

Although most of these medications are quite safe, he noted, physicians should wait for more risk/benefit studies before prescribing preemptive administration to women in the general population.

This study was funded by Duchesnay, the manufacturer of the doxylamine–pyridoxine combination. Dr. Silver has disclosed no relevant financial relationships.

Society for Maternal-Fetal Medicine (SMFM) 33rd Annual Meeting: Abstract 31. Presented February 14, 2013.