Bendectin and birth defects: Hopefully, the final chapter

Management of gastrointestinal and liver diseases during pregnancy

“…More specifically, combination therapy of doxylamine succinate (10 g) and vitamin B 6 (10 g) is recommended as first-line therapy for the treatment of nausea in pregnancy by the Canadian and American Colleges of Obstetricians and Gynecologists10 11 and the Association of Professors of Gynecology and Obstetrics 12. Moreover, two meta-analyses have confirmed the fetal safety of this therapy 13 14. There have also been several prospective studies of metoclopramide use in pregnancy that have not revealed any association with an increased risk of birth defects 15–17.…”

TheDaubertDecision

“…There were numerous cohort and case-control studies, 2 meta-analyses, and animal and in vitro studies, all of which indicated that the clinical use of Bendectin represented no measurable increased risk for birth defects in the exposed population. [4][5][6][7][8][9][10][11][12][13] Expert witnesses for the plaintiff have testified numerous times but have not subjected their testimony to peer review. It is important to understand that there is no scientific basis for testifying "with reasonable degree of medical certainty" that Bendectin causes congenital malformations as a general thesis or in an individual congenital-malformation lawsuit.…”

Antihistamines and birth defects: a systematic review of the literature

“…The most controversial antihistamine ever in widespread use in the United States, the combination of doxylamine plus pyridoxine (originally a three-component drug which also included dicyclomine [an antispasmodic]), was reformulated to the more commonly-used two-component version in 1976 after a double-blind evaluation demonstrated that dicyclomine did not contribute to the drug's effectiveness (reported in Brent, 2003) 4 . Sold in the United States from 1957-1983, an estimated 30-35% of pregnant women used doxylamine plus pyridoxine for the treatment of NVP during the height of its popularity the 1970s 4 .…”

“…Sold in the United States from 1957-1983, an estimated 30-35% of pregnant women used doxylamine plus pyridoxine for the treatment of NVP during the height of its popularity the 1970s 4 . However, because of concerns about fetal safety, doxylamine plus pyridoxine has been the topic of at least 27 original research peer-reviewed publications 5 , three published meta-analyses 5-7 , and at least 30 commentaries, editorials, and letters to the editor ( 4, 8-11 ). The meta-analysis by McKeigue and colleagues based on 16 cohort and 11 case-control studies reported a pooled relative risk showing no association between any birth defect and first trimester exposure to doxylamine plus pyridoxine (0.95; 95% confidence interval (CI) 0.88-1.04).…”

“…Separate analyses were conducted on types of birth defects including neural tube defects, oral clefts, congenital heart defects (CHD), and limb reductions, with relative risks ranging from 0.81 to 1.12, all of which had confidence intervals that contained the null value of 1.0 5 . However in the face of numerous lawsuits stating that the drug caused birth defects, including a class action case with over 1,000 plaintiffs, 4 its manufacturer stopped marketing doxylamine plus pyridoxine in the United States in 1983. As of April 2013, however, the US Food and Drug Administration has granted approval for a marketing a formulation of doxylamine plus pyridoxine for the treatment of NVP in women who do not respond to conservative management.…”