Is Ondansetron (Zofran) safe during pregnancy?

From the Guidelines

Zofran (ondansetron) is generally considered safe for use during pregnancy when prescribed by a healthcare provider. It's commonly used to treat severe nausea and vomiting in pregnancy, particularly when other treatments haven't worked. The typical dose is 4-8 mg taken orally every 8 hours as needed, though your doctor will determine the appropriate dosage for your situation.

Key Points to Consider

• While earlier concerns existed about potential birth defects, more recent and larger studies, such as the one published in Gastroenterology in 2024 1, have not found significant risks associated with ondansetron use during pregnancy.
• However, it should only be used when the benefits outweigh potential risks, and typically after trying other first-line treatments like vitamin B6 and doxylamine.
• Zofran works by blocking serotonin receptors in the brain and gut that trigger nausea and vomiting.
• Always consult with your healthcare provider before taking any medication during pregnancy, as they can evaluate your specific situation and medical history to determine if Zofran is appropriate for you.

Important Considerations

• A study published in Annals of Oncology in 2023 1 also supports the safety of ondansetron during pregnancy, noting a small absolute increase in orofacial and ventricular septal defects, but this risk is considered marginal.
• The American College of Gastroenterology and other medical guidelines recommend a step-up approach for managing nausea and vomiting in pregnancy, with ondansetron considered for severe cases or when first-line treatments are ineffective.
• It's crucial to follow the guidance of a healthcare provider, as they can assess individual risks and benefits, and monitor for any potential side effects or complications.

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 use of ondansetron in pregnancy is not conclusively established as safe due to inconsistent findings and methodological limitations in epidemiological studies. However, available data do not indicate a significant risk of miscarriage or adverse maternal outcomes. Animal studies have also not shown 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 to consider include:

• Inconsistent epidemiological study findings
• No identified drug-associated risk of miscarriage or adverse maternal outcomes
• Animal studies showing no harm to the fetus It is essential to weigh these factors and exercise caution when prescribing ondansetron to pregnant women.

From the Research

Zofran (Ondansetron) Use in Pregnancy

• Zofran, also known as ondansetron, is a medication used to treat nausea and vomiting in pregnancy 3, 4, 5, 6, 7.
• According to a 2016 study, ondansetron was associated with improved symptoms compared to placebo for moderate symptoms of nausea and vomiting in pregnancy 3.
• However, the European Medicines Agency (EMA) updated its assessment report in 2019, stating that ondansetron should not be used in the first trimester of pregnancy due to potential risks of congenital cardiac malformations and oral cleft 4.
• Other studies have found that ondansetron may be safe for use in pregnancy, with one study concluding that current data do not support a reluctance to treat women with ondansetron in clinical practice 6.
• The American College of Obstetricians and Gynecologists recommends early treatment of nausea and vomiting of pregnancy to stop progression to hyperemesis gravidarum, and ondansetron is an efficacious treatment used widely for this purpose 6.

Safety Considerations

• The safety of ondansetron during pregnancy has been a topic of debate, with some studies suggesting a potential increased risk of congenital cardiac malformations and oral cleft 4, 5.
• However, other studies have found that ondansetron may be safe for use in pregnancy, with large reassuring studies documenting fetal safety 5, 6.
• The quality of evidence on the safety of ondansetron in pregnancy is generally considered low, and more studies are needed to quantify fetal risks 3, 5.

Treatment Options

• Other treatment options for nausea and vomiting in pregnancy include ginger, vitamin B6, antihistamines, metoclopramide, and pyridoxine-doxylamine 3, 7.
• The choice of treatment should be based on the severity of symptoms and the individual patient's needs, with consideration of the potential risks and benefits of each treatment option 3, 5, 7.