Is Zofran (ondansetron) safe to use during pregnancy?

From the Guidelines

Zofran (ondansetron) is considered safe for use during pregnancy, particularly for severe nausea and vomiting, with the most recent guidelines suggesting its use as a second-line therapy 1. The medication works by blocking serotonin receptors in the brain and gut that trigger nausea. While earlier concerns existed about potential birth defects, particularly heart defects and cleft palate, more recent and larger studies, such as the 2024 study published in Gastroenterology, have largely found no significant increased risk with ondansetron use during pregnancy 1. Some studies, like the one referenced in the European Association for the Study of the Liver Clinical Practice Guidelines, note that ondansetron use in pregnancy has been associated with an increased rate of orofacial clefting, but the absolute risk remains low, increasing from 11 cases per 10,000 births to 14 cases per 10,000 births 1. Given this information, the benefits of treating severe nausea and vomiting with ondansetron often outweigh the potential risks, especially when other treatments have failed and the patient's health is at risk due to dehydration and malnutrition. Pregnant women should always consult with their healthcare provider before taking any medication, as individual risk factors may influence the decision. Key points to consider include:

• Typical dosing is 4-8 mg taken orally every 8 hours as needed, with a maximum daily dose of 24 mg.
• Other interventions, such as dietary changes, ginger supplements, vitamin B6, or doxylamine combinations, should be tried first.
• The decision to use ondansetron should be made on a case-by-case basis, considering the severity of symptoms and the patient's overall health. It's also important to note that ondansetron is recommended as a second-line therapy by ACOG, to be used only when first-line treatments are not effective, and its administration should be carefully considered, especially in the first trimester 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

The safety of Zofran (ondansetron) in pregnancy is not conclusively established due to inconsistent findings in epidemiological studies and methodological limitations. However, available data do not indicate a significant risk of major birth defects or adverse maternal outcomes 2. Animal studies have also shown no evidence of harm to the fetus at doses up to 6 and 24 times the maximum recommended human dose.

• Key points:
  • Inconsistent epidemiological study findings
  • No identified risk of miscarriage or adverse maternal outcomes
  • Animal studies show no harm to the fetus at high doses It is essential to weigh the potential benefits and risks of using ondansetron during pregnancy, and healthcare providers should make decisions on a case-by-case basis 2.

From the Research

Safety of Zofran (Ondansetron) in Pregnancy

• The safety of Zofran (ondansetron) during pregnancy is a topic of ongoing debate and research 3, 4, 5, 6.
• Some studies suggest that ondansetron may be associated with an increased risk of orofacial clefts and congenital heart defects in fetuses exposed in utero during the 1st trimester of pregnancy 3, 4.
• However, other studies have found no significant increase in the risk of miscarriage or other adverse outcomes with ondansetron use during pregnancy 5, 6.
• The European Medicines Agency has stated that ondansetron should not be used during the 1st trimester of pregnancy due to potential risks 3.
• The US Food and Drug Administration (FDA) has also issued warnings about the potential risks of ondansetron use during pregnancy, including QT prolongation and torsade de pointes 4.

Efficacy and Safety of Ondansetron in Clinical Trials

• A systematic review of clinical trials found that ondansetron is an effective treatment for nausea and vomiting, including pregnancy-related morning sickness 5.
• However, the review also noted that further research is needed to fully understand the potential risks and benefits associated with ondansetron use in pregnant women 5.
• Another study found that ondansetron use in early pregnancy was not associated with an increased risk of miscarriage compared to alternative antiemetics 6.

Precautions and Considerations

• Pregnant women should discuss the potential risks and benefits of ondansetron use with their healthcare provider before taking the medication 3, 4.
• Alternative treatments for nausea and vomiting during pregnancy, such as doxylamine-pyridoxine, may be considered 4.
• Healthcare providers should carefully weigh the potential benefits and risks of ondansetron use in pregnant women and monitor them closely for any adverse effects 3, 4.