Is Ondansetron (Zofran) safe during pregnancy?

From the Guidelines

Zofran (ondansetron) is considered safe for use during pregnancy when needed to treat severe nausea and vomiting, including hyperemesis gravidarum, as stated in the most recent study from 2024 1. The typical dosage is 4-8 mg taken orally every 8 hours as needed, though your healthcare provider may adjust this based on your specific situation. While earlier concerns existed about potential birth defects, more recent and larger studies have not found significant associations between ondansetron use and major birth defects, as noted in the 2023 study 1. However, as with any medication during pregnancy, it should only be used when the benefits outweigh potential risks. Zofran works by blocking serotonin receptors in the brain and gut that trigger nausea and vomiting. Some key points to consider when using Zofran during pregnancy include:

• The American College of Obstetricians and Gynecologists (ACOG) recommends a step-up approach for patients who do not respond to first-line therapy, with metoclopramide and ondansetron as potential options 1.
• Ondansetron is given primarily in severe NVP that requires hospitalization, and has not been associated with an increased risk of stillbirth, spontaneous abortion, or major birth defects, as stated in the 2024 study 1.
• The European Association for the Study of the Liver Clinical Practice Guidelines recommend doxylamine and pyridoxine and phenothiazines as first-line pharmacologic treatment of HG and metoclopramide and ondansetron as second-line therapies 1. Always consult with your healthcare provider before taking any medication during pregnancy, as they can evaluate your specific situation and help determine if Zofran is appropriate for you.

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

The safety of ondansetron in pregnancy is not conclusively established due to inconsistent findings and methodological limitations in epidemiological studies 2 2. However, available data do not suggest a significant risk of miscarriage or adverse maternal outcomes.

• Key findings:
  • Inconsistent epidemiological study results
  • No identified risk of miscarriage or adverse maternal outcomes
  • Reproductive studies in animals showed no harm to the fetus
• Clinical decision: Use ondansetron in pregnancy with caution, considering the potential benefits and risks, as the safety profile is not fully established 2 2.

From the Research

Safety of Zofran (Ondansetron) in Pregnancy

• The American College of Obstetricians and Gynecologists recommends early treatment of nausea and vomiting of pregnancy to prevent progression to hyperemesis gravidarum 3.
• Ondansetron is a widely used treatment for nausea and vomiting of pregnancy, but its safety during pregnancy has been debated due to conflicting findings in recent studies 3, 4.
• A study published in 2016 found that current data do not support a reluctance to treat women with ondansetron in clinical practice, despite limitations in the literature on its safety 3.
• However, another study published in 2012 suggested that ondansetron use cannot be assumed to be safe during pregnancy due to limited fetal safety data and potential risks of QT prolongation and torsade de pointes 4.

Efficacy of Ondansetron in Treating Nausea and Vomiting in Pregnancy

• A randomized trial published in 2013 found that ondansetron was more effective than metoclopramide in controlling severe vomiting in pregnant women 5.
• A systematic review published in 2016 found that ondansetron was associated with improved symptoms of nausea and vomiting in pregnancy, particularly for moderate symptoms 6.
• The review also found that other interventions, such as ginger, vitamin B6, antihistamines, and metoclopramide, were associated with improved symptoms, but the quality of evidence was generally low 6.

Considerations for Treatment

• The decision to use ondansetron or other treatments for nausea and vomiting in pregnancy should be made on a case-by-case basis, taking into account the severity of symptoms and potential risks and benefits 3, 6.
• Healthcare providers should be proactive in diagnosing and managing nausea and vomiting in pregnancy, and patients should be involved in the decision-making process 7.