Can Ondansetron (Zofran) be given during pregnancy?

From the Guidelines

Ondansetron (Zofran) can be used during pregnancy when necessary for managing severe nausea and vomiting, particularly in hyperemesis gravidarum when other treatments have failed, as it has been shown to be effective with no significant increased risk of major congenital malformations in recent studies 1. The typical dose is 4-8 mg orally or intravenously every 8 hours as needed. While initial concerns existed about potential birth defects, more recent and larger studies, such as the 2024 study published in Gastroenterology 1, have generally shown no significant increased risk of major congenital malformations with ondansetron use during pregnancy. However, it is still considered a second-line treatment after trying other options like vitamin B6 (10-25 mg three times daily) and doxylamine (12.5 mg three to four times daily). Some key points to consider when using ondansetron during pregnancy include:

• The European Association for the Study of the Liver Clinical Practice Guidelines recommend ondansetron as a second-line therapy for hyperemesis gravidarum 1
• Ondansetron works by blocking serotonin receptors in the brain and gut that trigger nausea and vomiting, providing effective relief when other treatments are insufficient
• The decision to use ondansetron should be made after discussing the benefits versus potential risks with your healthcare provider, considering the severity of symptoms and the importance of maintaining maternal nutrition and hydration during pregnancy. It's also worth noting that ondansetron has been associated with an increased rate of orofacial clefting, but the absolute risk is relatively low, increasing from 11 cases per 10,000 births to 14 cases per 10,000 births 1.

From the FDA Drug Label

Published epidemiological studies on the association between ondansetron use and major birth defects have reported inconsistent findings and have important methodological limitations that preclude conclusions about the safety of ondansetron use in pregnancy Available postmarketing data have not identified a drug associated risk of miscarriage or adverse maternal outcomes. Reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered during organogenesis at approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, based on body surface area (BSA), respectively

Ondansetron use in pregnancy is not conclusively determined to be safe due to inconsistent findings and methodological limitations in epidemiological studies. However, available data do not suggest a significant risk of major birth defects or adverse maternal outcomes. Animal studies have also shown no evidence of harm to the fetus. Therefore, ondansetron may be used in pregnancy if clinically necessary, but with caution and careful consideration of the potential risks and benefits 2.

• Key points:
  • Inconsistent findings in epidemiological studies
  • No significant risk of major birth defects or adverse maternal outcomes
  • Animal studies show no evidence of harm to the fetus
  • Use with caution and careful consideration of potential risks and benefits

From the Research

Zofran Use in Pregnancy

• Zofran, also known as ondansetron, is a medication used to treat nausea and vomiting in pregnancy 3, 4, 5, 6, 7.
• The European Medicines Agency has stated that ondansetron should not be used in the first trimester of pregnancy due to potential risks of orofacial clefts and congenital heart defects 3, 5.
• However, some studies suggest that ondansetron may be effective in treating nausea and vomiting in pregnancy, particularly in cases where other treatments have failed 4, 6, 7.
• A systematic review of 78 studies found that ondansetron was associated with improved symptoms compared to placebo, but the quality of evidence was low 4.
• Another study found that ondansetron was associated with lower nausea scores and fewer episodes of emesis compared to metoclopramide, but the difference was not significant 7.
• The use of ondansetron in pregnancy is still a topic of debate, and more research is needed to fully understand its safety and efficacy 3, 5, 6.

Safety and Efficacy

• The safety of ondansetron in pregnancy has been questioned due to potential risks of congenital malformations 3, 5.
• However, some studies have found that ondansetron is not associated with an increased risk of adverse outcomes 4, 7.
• The efficacy of ondansetron in treating nausea and vomiting in pregnancy has been demonstrated in several studies, but the quality of evidence is often low 4, 6, 7.
• More research is needed to fully understand the safety and efficacy of ondansetron in pregnancy and to inform clinical decision-making 3, 5, 6.

Clinical Guidelines

• Clinical guidelines for the treatment of nausea and vomiting in pregnancy vary, but often recommend ondansetron as a second-line treatment option 3, 4, 6.
• The European Medicines Agency has updated its guidance to recommend against the use of ondansetron in the first trimester of pregnancy 3, 5.
• However, some clinicians and researchers argue that the evidence for this recommendation is not sufficient, and that ondansetron may still be a useful treatment option for some women 5, 6.