The Delayed-Release Combination of Doxylamine and Pyridoxine (Diclegis®/Diclectin®) for the Treatment of Nausea and Vomiting of Pregnancy

Abstract

Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman’s quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs. Unfortunately, many women receive either no pharmacological treatment or are recommended therapies for which fetal safety and efficacy have not been established. First-line treatment of NVP, as recommended by several leading healthcare and professional organizations, is the combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed-release tablet, was approved by the US Food and Drug Administration (FDA) for the treatment of NVP in April 2013 under the brand name Diclegis®, and has been on the Canadian market since 1979, currently under the brand name Diclectin®. The efficacy of Diclegis®/Diclectin® has been demonstrated in several clinical trials, and, more importantly, studies on more than 200,000 women exposed to doxylamine and pyridoxine in the first trimester of pregnancy have demonstrated no increased fetal risk for congenital malformations and other adverse pregnancy outcomes. The present review aims to present the scientific evidence on the effectiveness and fetal safety of Diclegis®/Diclectin® for the treatment of NVP to justify its use as first-line treatment for NVP.

Hyperemesis Gravidarum: A Review of Recent Literature

“…Doxylamine succinate is an antihistamine (H1 blocker), which is responsible for the drug's sedative and anti-emetic effects and 10 mg pyridoxine HCl is a formulation of vitamin B6. Vitamin B6 is known to be utilized by the body in over 160 enzyme activities including metabolic processes of amino acids, nucleic acids, unsaturated fatty acids, carbohydrates, glycogen, neurotransmitters, and porphyrin, and therefore thought to be a beneficial supplement in patients with a depleted nutritional state [40]. The safety of the drug has been extensively analyzed prior to its rerelease in the United States, as it had been continuously offered in Canada and Europe.…”

“…Due to the expense of the patented formulation, patients and physicians have attempted multiple off-brand alternatives including off-label use of over-the-counter 12.5 mg doxylamine (0.5 tablets of 25 mg) plus 10-25 mg pyridoxine; however, due to the nondelayed formulation of these alternatives, the efficacy of treatment appears diminished. Most studies, cite the effectiveness of Diclegis in cases classified as “nausea and vomiting” of pregnancy to be between 70 and 80% [40]. To date, Diclegis has not been studied specifically in patients with hyperemesis gravidarum.…”

Nausea and vomiting of pregnancy - What's new?

“…The delayed-release tablet contains doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg (Koren et al, 2010 ). This drug combination has been widely used in different countries around the world (Zur, 2013) and several studies and meta-analyses over the last 3 decades support its efficacy (2004; Niebyl et al, 2002) as well as its fetal and maternal safety (Einarson et al, 1988; Holmes, 1983; Koren et al, 2015; Madjunkova et al, 2014; McKeigue et al, 1994). Drowsiness is the most common side effect reported for this drug (Sanu et al, 2011).…”

8-Way Randomized Controlled Trial of Doxylamine, Pyridoxine and Dicyclomine for Nausea and Vomiting during Pregnancy: Restoration of Unpublished Information

“…Several sources have cited this trial in support of doxylamine and pyridoxine for the treatment of nausea and vomiting during pregnancy [9–12, 17]. In 2013, the US FDA referred to the results of this trial in approving a product containing doxylamine and pyridoxine: “…this reviewer concurs that the 1975 ‘8-way’ study supports the effectiveness of Diclegis in the treatment of NVP.” This recent US FDA review quoted the results of this 8-way study (e.g.…”