title: Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial.
abstract: BACKGROUND
  Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting up to 80% of expecting mothers. In April 2013 the FDA approved the delayed release combination of doxylamine succinate and -pyridoxine hydrochloride (Diclegis®) for NVP, following a phase 3 randomized trial in pregnant women. The fetal safety of this medication has been proven by numerous studies. However, because it is the only FDA-approved medication for NVP that is likely to be used by a large number of pregnant women, its maternal safety is an important public health question. The Objective is to evaluate the maternal safety of doxylamine succinate -pyridoxine hydrochloride delayed-release preparation (Diclegis® as compared to placebo.
  
  
  METHODS
  We randomized women suffering from NVP to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from 2-4 tablets a day, based on a pre-specified titration protocol response to symptoms. Adverse events were collected through patient diaries, clinical examination and laboratory testing.
  
  
  RESULTS
  Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg use was not associated with an increased rate of any adverse event over placebo, including CNS depression, gastrointestinal or cardiovascular involvement.
  
  
  CONCLUSIONS
  Doxylamine succinate-pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy.
  
  
  BACKGROUND
  Clinical Trial Registration No: NCT00614445 .
authors.affiliation: From the Motherisk Program, Hospital for Sick Children and University of Toronto, Toronto, Canada. gkoren@sickkids.ca.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA. gkoren@sickkids.ca.|Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. gkoren@sickkids.ca.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas, Medical Branch Galveston, Galveston, TX, USA. shclark@utmb.edu.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA. shclark@utmb.edu.
authors.forename: Shannon
authors.initials: S
authors.lastname: Clark
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas, Medical Branch Galveston, Galveston, TX, USA. ghankins@utmb.edu.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA. ghankins@utmb.edu.
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: Department of Obstetrics and Gynecology, University of Pittsburgh, Medical Center, Pittsburgh, PA, USA. carisn@mail.magee.edu.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA. carisn@mail.magee.edu.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
authors.affiliation: Medstar Health Research Institute, Hyattsville MD, and the Georgetown- Howard Universities Center for Clinical and Translational Science, Washington, DC, USA. Jason.umans@gmail.com.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA. Jason.umans@gmail.com.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.affiliation: Medstar Health Research Institute, Hyattsville MD, and the Georgetown- Howard Universities Center for Clinical and Translational Science, Washington, DC, USA. mmiodovnik@gmail.com.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA. mmiodovnik@gmail.com.
authors.forename: Menachem
authors.initials: M
authors.lastname: Miodovnik
authors.affiliation: The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA. Donald.mattison@gmail.com.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Mattison
authors.affiliation: From the Motherisk Program, Hospital for Sick Children and University of Toronto, Toronto, Canada. ilanmatok@gmail.com.|Division of Clinical Pharmacy, Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. ilanmatok@gmail.com.
authors.forename: Ilan
authors.initials: I
authors.lastname: Matok
mesh_terms: D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004025:Dicyclomine / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004319:Doxylamine / Q000008:administration & dosage / Q000009:adverse effects; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D009325:Nausea / Q000188:drug therapy / Q000209:etiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011736:Pyridoxine / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014803:Vitamin B Complex; D014839:Vomiting / Q000188:drug therapy / Q000209:etiology
chemical_list: D000932:Antiemetics; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; C004454:dicyclomine, doxylamine, pyridoxine drug combination; D014803:Vitamin B Complex; D004025:Dicyclomine; D004319:Doxylamine; D011736:Pyridoxine