Duchesnay USA's Diclegis

Diclegis (doxylamine succinate and pyridoxine hydrochloride) has been approved by the FDA for the treatment of nausea and vomiting associated with pregnancy.

On April 8, 2013, the FDA announced approval of Diclegis (doxylamine succinate and pyridoxine hydrochloride) for nausea and vomiting associated with pregnancy. It may be used in pregnant women with nausea and vomiting that does not improve with conservative management strategies; however, it has not been studied in pregnant women with hyperemesis gravidarum,¹ a condition that causes extreme, persistent nausea often associated with dehydration.²

The components of Diclegis have been used since 1976 to treat morning sickness in the United States and around the world. Currently, Diclegis is the only FDA-approved treatment for nausea and vomiting associated with pregnancy.^1,3

Pharmacology and Pharmacokinetics

The mechanism of action of Diclegis is unknown.¹

Peak plasma concentrations of the doxylamine component occur in 7.5 hours, and the pyridoxine component, 5.5 hours. Elimination half-life is 12.5 hours for the doxylamine component, and in 0.5 hours for the pyridoxine component. Steady-state concentrations of doxylamine are reached within 24 to 48 hours. Pyridoxine does not reach steady-state concentrations due to its short half-life.¹

Dosage and Administration

Each tablet contains 10 mg of doxylamine succinate and 10 mg of pyridoxine hydrochloride, should not be chewed or crushed, and should be taken on an empty stomach with a glass of water. Patients should start with 2 tablets daily at bedtime, adding a single-tablet morning dose if symptoms are inadequately controlled. If further symptoms occur, patients may add a single-tablet midafternoon dose to the regimen, reaching the 4-tablet maximum daily dose.¹

Clinical Trials

Two meta-analyses evaluated the results of several cohort and case control studies carried out between 1961 and 1985, and failed to detect any teratogenicity to the components of Diclegis related to use during the first trimester of pregnancy. Further studies in pregnant rhesus monkeys confirmed the safety of these medications.¹

In a clinical trial of pregnant, adult women between 7 and 14 weeks’ gestation, 131 patients received between 2 and 4 tablets daily and 125 patients received placebo for 14 days. Investigators evaluated the degree of nausea with a survey called the Pregnancy Unique-Quantification of Emesis (PUQE) that rated the degree of emesis from 3 (no emesis) to 15 (6 or more hours of nausea, 7 or more instances of vomiting, and 7 or more instances of dry heaves daily). Treatment with placebo led to a 3.9-point mean decrease in the PUQE score by day 15, while patients treated with Diclegis experienced an additional 0.7-point mean decline in PUQE scores over patients treated with placebo (95% CI: 0.2-1.2; P <.0006).^1,4

Contraindications, Warnings, and Precautions

Diclegis is contraindicated in patients with a hypersensitivity to ethanolamine-based antihistamines, pyridoxine hydrochloride, or any inactive components of Diclegis. Patients should avoid tasks such as operating machinery or driving. Alcohol should be avoided because it may increase the sedation potential of Diclegis. Medical conditions such as asthma, increased intraocular pressure, narrow-angle glaucoma, certain stomach problems, and bladder obstruction problems should be discussed with a health care professional before initiating treatment because the anticholinergic properties of doxylamine may affect these conditions.¹

Although Diclegis is a category A medication for use in pregnancy, it should not be used during breast-feeding because the doxylamine component may cause sedation and worsening of respiratory conditions in infants. Excitement and irritability may also occur with doxylamine exposure in infants. In clinical trials, 14.3% of patients using Diclegis experienced somnolence versus 11.7% of patients using placebo, meaning investigators would have to treat ≈38 patients with Diclegis instead of placebo for 1 additional case of somnolence to occur. Other adverse events observed in postmarketing experience include tachycardia, blurred vision, vertigo, irritability, migraine, urinary retention, and rash.¹

Michael R. Page earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.

References:

• Diclegis (doxylamine succinate and pyridoxine hydrochloride) [package insert]. Bryn Mawr, PA: Duchesnay USA, Inc; 2013.
• US National Library of Medicine. Hyperemesis gravidarum. www.nlm.nih.gov/medlineplus/ency/article/001499.htm. Accessed June 2013.
• US Food and Drug Administration. FDA approves Diclegis for pregnant women experiencing nausea and vomiting. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm347087.htm. Accessed June 2013.
• Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010;6(571):e1-e7.