Is Ondansetron (Zofran) safe to use during pregnancy?

From the Guidelines

Ondansetron (Zofran) can be used in pregnancy for nausea and vomiting when benefits outweigh risks, as it has not been associated with an increased risk of stillbirth, spontaneous abortion, or major birth defects, although it should be administered with caution in the first trimester due to some reports of congenital heart defects 1.

Key Considerations

• The American College of Obstetricians and Gynecologists (ACOG) recommends a step-up approach for patients who do not respond to first-line therapy, with ondansetron given primarily in severe nausea and vomiting that requires hospitalization 1.
• A recent study published in Gastroenterology suggests that ondansetron should only be administered as a second-line therapy, and ACOG recommends using it on a case-by-case basis in patients with persistent symptoms before 10 weeks of pregnancy 1.
• Another study published in Annals of Oncology states that ondansetron, metoclopramide, and steroids are considered safe for use during pregnancy for nausea and vomiting 1.

Treatment Approach

• The typical dose of ondansetron is 4-8 mg orally every 8 hours as needed, with a maximum daily dose of 24 mg.
• Patients should be informed that while the medication appears relatively safe in pregnancy, the decision to use it should involve weighing the severity of symptoms against potential risks, and should be made in consultation with their healthcare provider.
• Other interventions, such as dietary changes, ginger, vitamin B6, or doxylamine-pyridoxine combinations (Diclegis/Bonjesta), should be tried first before considering ondansetron.

Important Notes

• Ondansetron works by blocking serotonin receptors that trigger nausea and vomiting pathways in both the brain and gut.
• The medication is not FDA-approved specifically for morning sickness, but is commonly used off-label for this purpose.
• While most studies show no significant increase in birth defects with ondansetron use, some research has suggested a small potential increased risk of oral clefts when used in the first trimester, and therefore it should be used with caution in this period 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 ondansetron (Zofran) use during pregnancy is uncertain due to inconsistent findings and methodological limitations in epidemiological studies. However, animal studies have not shown evidence of harm to the fetus.

• Key points:
  • Inconsistent findings in epidemiological studies
  • No drug-associated risk of miscarriage or adverse maternal outcomes in postmarketing data
  • Animal studies did not show evidence of harm to the fetus Based on the available data, a conservative clinical decision would be to use ondansetron with caution during pregnancy, as the evidence is unclear or equivocal 2.

From the Research

Safety of Ondansetron During Pregnancy

• The safety of ondansetron during pregnancy is a topic of ongoing debate, with some studies suggesting an increased risk of orofacial clefts and congenital heart defects in fetuses exposed to the drug in the first trimester 3.
• However, other studies have found ondansetron to be safe and effective in treating nausea and vomiting during pregnancy, with a low risk of adverse effects 4, 5.
• The European Medicines Agency has stated that ondansetron should not be used during the first trimester of pregnancy due to the potential risks, but this decision is controversial 3.
• A 2024 study published in the BJOG: an international journal of obstetrics and gynaecology found that ondansetron can be used as a second-line antiemetic in pregnant women with severe vomiting, with a low risk of adverse effects 4.
• Another study published in 2013 found that ondansetron was more effective than metoclopramide in controlling severe vomiting in pregnant women 5.

Risks and Benefits

• The risks of using ondansetron during pregnancy must be weighed against the benefits of treating nausea and vomiting, which can have serious consequences for the health of the mother and fetus if left untreated 4, 6.
• Pregnant women should be informed of the potential risks and benefits of ondansetron and other antiemetic medications, and should be closely monitored for any adverse effects 4, 7.
• Further research is needed to fully understand the safety and efficacy of ondansetron and other medications during pregnancy, and to develop new treatments for obstetric conditions 6.