Doxylamine succinate-pyridoxine hydrochloride (Diclegis) for the management of nausea and vomiting in pregnancy: an overview

Abstract

Nausea and vomiting in pregnancy (NVP) is common and often undertreated, in part due to fears of adverse effects of medications on the fetus during early pregnancy. In April 2013, the US Food and Drug Administration (FDA) approved doxylamine succinate 10 mg and pyridoxine hydrochloride (a vitamin B6 analog) 10 mg as a delayed-release combination pill called Diclegis for the treatment of NVP. Diclegis is currently the only medication that is FDA-approved for the indication of NVP. This review addresses the historical context, safety, efficacy, pharmacology, and practical role of doxylamine and pyridoxine for the management of NVP. The reintroduction of this doxylamine-pyridoxine combination pill into the American market fills a therapeutic gap in the management of NVP left by the removal of the same active drugs marketed over 30 years ago in the form of Bendectin. The substantial amount of safety data accumulated over the years makes it one of the few drugs that qualify for FDA Pregnancy Category A status. In the hierarchical approach to pharmacological treatment of NVP, the combination of doxylamine and pyridoxine should thus be first-tier.

Keywords: doxylamine; nausea; pregnancy; pyridoxine; vitamin B6; vomiting.

Figure 1

Public health data related to Bendectin therapy. Notes: NVP hospitalization data were collected by the National Center for Health Statistics. Birth defect data were collected by the Centers for Disease Control. Bendectin sales data were collected by the Food and Drug Administration. Reproduced with permission from Kutcher JS, Engle A, Firth J, Lamm SH. Bendectin and birth defects. II: Ecological analyses. Birth Defects Res A Clin Mol Teratol. 2003;67(2):88–97. © 2003 Wiley-Liss, Inc., A Wiley Company. Abbreviation: NVP, nausea and vomiting in pregnancy.

Figure 2

ACOG (American Congress of Obstetricians and Gynecologists) algorithm for pharmacologic treatment of NVP (Nausea and vomiting in pregnancy). Notes: *This algorithm assumes other causes of nausea and vomiting have been ruled out. At any step, consider parenteral nutrition if dehydration or persistent weight loss is noted. Alternative therapies may be added at any time during the sequence depending on patient acceptance and clinician familiarity; consider P6 acupressure with wrist bands or acustimulation or ginger capsules, 250 mg 4 times daily; ^†in the United States, doxylamine is available as the active ingredient in some over-the-counter sleep aids; one half of a scored 25 mg tablet can be used to provide a 12.5 mg dose of doxylamine; ^‡thiamine, intravenously, 100 mg daily for 2–3 days (followed by intravenous multivitamins), is recommended for every woman who requires intravenous hydration and has vomited for more than 3 weeks; ^$corticosteroids appear to increase risk for oral clefts in the first 10 weeks of gestation; ^¶safety, particularly in the first trimester of pregnancy, not yet determined; less effect on nausea.