What is the safety of Zofran (ondansetron) during pregnancy?

From the Guidelines

Ondansetron is generally considered safe during pregnancy, but its use should be approached with caution, especially in the first trimester.

Safety of Ondansetron

• The American College of Obstetricians and Gynecologists (ACOG) recommends using ondansetron on a case-by-case basis in patients with persistent symptoms before 10 weeks of pregnancy 1.
• A study published in the Journal of Hepatology found that ondansetron use in pregnancy has been associated with an increased rate of orofacial clefting, but the absolute risk is still relatively low, increasing from 11 cases per 10,000 births to 14 cases per 10,000 births 1.
• The European Association for the Study of the Liver Clinical Practice Guidelines recommend ondansetron as a second-line therapy for hyperemesis gravidarum, citing its effectiveness and relatively safe profile 1.

Key Considerations

• First-trimester use: While ondansetron can be used in the first trimester, it should be done so with caution and only when the benefits outweigh the potential risks 1.
• Dosing and administration: The dosage and administration of ondansetron should be carefully considered, and patients should be monitored for any adverse effects 1.
• Alternative treatments: Other anti-emetic agents, such as metoclopramide and promethazine, may be considered as first-line treatments for hyperemesis gravidarum, depending on the patient's specific needs and medical history 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) during pregnancy is uncertain. While some studies suggest no increased risk of major birth defects or adverse outcomes, others have reported inconsistent findings. No conclusive evidence is available to fully assess the safety of ondansetron use in pregnancy 2.

From the Research

Safety of Zofran (Ondansetron) During Pregnancy

The safety of Zofran (ondansetron) during pregnancy has been a topic of considerable debate. Several studies have investigated the potential risks associated with the use of ondansetron during pregnancy, including the risk of congenital malformations and other adverse pregnancy outcomes.

Risk of Congenital Malformations

• A study published in 2020 found that first trimester exposure to ondansetron was associated with an increased risk of ventricular septal defects (VSD) and oral clefts 3.
• Another study published in 2020 found that early gestational exposure to ondansetron was associated with an increased risk of heart defects and orofacial defects, although the absolute increase in risk was small 4.
• A systematic review and meta-analysis published in 2022 found that the use of ondansetron during pregnancy was associated with an increased incidence of cardiac defects, neural tube defects, and chest cleft, although the results were not consistent across all studies 5.

Regulatory Updates

• The European Medicines Agency (EMA) updated the Summary of Product Characteristics (SmPC) for ondansetron in 2019 to state that it should not be used in the first trimester of pregnancy, citing concerns about the risk of congenital malformations 6.

Efficacy and Safety of Ondansetron

• A systematic review of clinical trials published in 2023 found that ondansetron was an effective treatment for nausea and vomiting, including pregnancy-related morning sickness, although further research is needed to fully understand the potential risks and benefits associated with its use 7.
• A study published in 2022 found that the use of ondansetron during pregnancy was associated with a reduced incidence of miscarriage, although the results were not consistent across all studies 5.

Overall Assessment

The available evidence suggests that the use of ondansetron during pregnancy may be associated with an increased risk of certain congenital malformations, although the absolute increase in risk is small. However, the evidence is not consistent across all studies, and further research is needed to fully understand the potential risks and benefits associated with the use of ondansetron during pregnancy 6, 3, 4, 7, 5.