Clinical Conundrum: Pregnant and Puking: What’s Safe and Effective in the ED?

Treatment of nausea and vomiting of pregnancy with vitamin B6 (pyridoxine) alone or vitamin B6 (pyridoxine) plus doxylamine in combination is safe and effective and should be considered first-line pharmacotherapy (ACOG Practice Bulletin 2018). For those not tolerating PO, other alternatives such as antihistamines, dopamine antagonists, and serotonin antagonists can be used. It is important to discuss with your patient and to be aware of the potential risks and side effects of each medication regimen. The following table outlines medications, dosages, route, and additional information for several medications we use in the Emergency Department:

Previous pregnancy risk categories:

• Category A: No risk in human studies (studies in pregnant women have not demonstrated a risk to the fetus during the first trimester).
• Category B: No risk in animal studies (there are no adequate studies in humans, but animal studies did not demonstrate a risk to the fetus).
• Category C: Risk cannot be ruled out. There are no satisfactory studies in pregnant women, but animal studies demonstrated a risk to the fetus; potential benefits of the drug may outweigh the risks. 
• Category D: Evidence of risk (studies in pregnant women have demonstrated a risk to the fetus; potential benefits of the drug may outweigh the risks).
• Category X:  Contraindicated (studies in pregnant women have demonstrated a risk to the fetus, and/or human or animal studies have shown fetal abnormalities; risks of the drug outweigh the potential benefits).
  

The Pregnancy and Lactation Labeling Rule (PLLR), implemented by the FDA in 2015, replaced the previous letter category system (A, B, C, D, X) with a more detailed narrative format. This change aimed to provide clearer, evidence-based information about the risks and benefits of medication use during pregnancy, lactation, and reproductive potential. The new labeling includes three sections—Pregnancy, Lactation, and Females and Males of Reproductive Potential—offering data on drug effects, clinical considerations, and supporting studies.

Ondansetron and concerns for birth defects:

Studies evaluating ondansetron and the risk of birth defects have been inconsistent. In a 2013 study of over 600,000 pregnancies (Pasternak 2013) reported that ondansetron was not associated with an increased risk of miscarriage, stillbirth, preterm delivery, low-birth-weight infants, small-for-gestational-age infants, or any major birth defects. A 2016 systematic review (Carstairs 2016) concluded that there was no overall increased risk of cardiac defects in ondansetron-exposed neonates, even though two of the included studies did show a small increase in cardiac malformations. Two studies released after this systematic review (Huybrechts 2018, Zambelli-Weiner 2019) showed no association of ondansetron use with overall cardiac malformations or congenital malformations, but did show a slight increase in cleft palate (an additional 5 cases/10,000 exposed births) and renal agenesis-dysgenesis. A 2019 cohort study (Huybrechts 2019) evaluating the use of intravenous ondansetron specifically showed no association with cardiac malformations, oral clefts, or overall congenital malformations.

Caputo Pearl:

Both Diclegis (10 mg Doxylamine succinate, 10 mg pyridoxine hydrochloride) and Bonjesta (extended-release 20 mg Doxylamine succinate, 20 mg pyridoxine hydrochloride) can be expensive prescriptions that insurance may not cover. Both medications can cost up to $500 per month without insurance or rebates. Pyridoxine (Vitamin B6) and Doxylamine (as Unisom) can be bought separately and is cheaper. The cost for regular use can be brought down to about ~ $30/month.