The majority of prescriptions used for the treatment of nausea and vomiting in pregnancy (NVP) in the United States have been with medications not labeled for and not classified as safe in use during pregnancy by the Food and Drug Administration. Over the last decade, the extremely potent 5HT3 receptor antagonist, Ondansetron (Zofran) has been increasingly used for NVP. However, the FDA has cautioned against its use in pregnancy based on recent studies regarding the association between Zofran use in early pregnancy and congenital cardiac malformations and oral clefts (cleft lip and palate). In addition, Zofran poses maternal risk of arrhythmias from possible QT interval prolongation which can result in the potentially fatal arrhythmia (Torsades de pointes) and Serotonin syndrome. The American College of Obstetricians and Gynecologists (ACOG) has issued new guidelines for the diagnosis and management of NVP. A safe and effective category A drug is available in the U.S., Diclegis (doxylamine succinate and Vitamin B6, pyridoxine hydrochloride) which has been studied in hundreds of thousands of pregnant women. Unisom SleepTabs (Sanofi Aventis; oral vitamin B6 and doxylamine), which are available OTC in the U.S., have been studied in more than 6000 patients and control participants, with no evidence of teratogenicity. In randomized trials, this combination has been associated with a 70% reduction in nausea and vomiting. ACOG therefore recommends this combination as first-line therapy for NVP. Following treatment failure with dietary modifications and alternative therapy remedies such as ginger capsules (250 mg qid) and acupuncture, pharmacologic therapies should include: 1. Vitamin B6 (pyridoxine), 10 to 25 mg every 8 hours, and doxylamine, 25 mg at bedtime and 12.5 mg each in the morning and afternoon. 2. If parental antiemetics are required, phenothiazides such as prochlorperazine or promethazine or Ondansetron in refractory cases. 3. Prokinetic agent Metoclopramide (Reglan; tablets, Alaven; injection, Baxter) is a dopamine antagonist. The FDA has issued a black-box warning concerning the use of Reglan in general. Because the risk for exrapyramidal complications, tardive dyskinesia increases with the duration of treatment and the total cumulative dose, treatment duration should not exceed 12 weeks. 4. Intravenous fluid replacement with multivitamins, especially thiamine is indicated with use of dextrose containing solutions (to prevent Wernicke's encephalopathy) until ketosis resolves.
References
1.Koren G. Am J Obstet Gynecol. 2014 Dec;211(6):602-6. doi: 10.1016/j.ajog.2014.08.017. Epub 2014 Aug 20. Treating morning sickness in the United States--changes in prescribing are needed. 2. Nulman I, Rovet J, et al. J Pediatr. 2009 Jul;155(1):45-50, 50.e1-2. doi: 10.1016/j.jpeds.2009.02.005. Epub 2009 Apr 24. Long-term neurodevelopment of children exposed to maternal nausea and vomiting of pregnancy and diclectin. 3. Slaughter SR, Hearns-Stokes R, et al. N Engl J Med. 2014 Mar 20; 370(12):1081-3. FDA approval of doxylamine-pyridoxine therapy for use in pregnancy. 4. Persaud N, Chin J, Walker M. J Obstet Gynaecol Can. 2014 Apr; 36(4):343-8. Should doxylamine-pyridoxine be used for nausea and vomiting of pregnancy?
