Is it safe to take Zofran (ondansetron) during pregnancy?

From the Guidelines

Zofran (ondansetron) can be used during pregnancy for managing severe nausea and vomiting, particularly in cases of hyperemesis gravidarum, as the benefits often outweigh the potential risks, and it is generally considered acceptable when used under the guidance of a healthcare provider. The medication is typically prescribed at doses of 4-8 mg taken orally every 8 hours as needed 1. While no medication during pregnancy is completely without risk, multiple large studies have shown that ondansetron does not significantly increase the overall risk of birth defects, although a marginal relative increase in cleft palate and cardiovascular malformations has been described 1.

Key Considerations

• The use of ondansetron in early pregnancy has not been linked to a high risk of congenital defects, but a small absolute increase in orofacial and ventricular septal defects has been reported 1.
• It is essential to weigh the benefits and potential risks of using Zofran during pregnancy, considering the severity of symptoms and pregnancy history.
• Healthcare providers should evaluate each case individually to determine if Zofran is appropriate, ideally after trying other safer options first, such as vitamin B6 and doxylamine 1.

Management Approach

• The American College of Obstetricians and Gynecologists (ACOG) recommends a step-up approach for managing nausea and vomiting during pregnancy, with ondansetron considered for severe cases that do not respond to first-line therapy 1.
• Metoclopramide can also be used for nausea and vomiting, with no increased risk of congenital defects reported, although it may cause extrapyramidal adverse effects 1.
• Methylprednisolone can be given as a last resort in patients with severe hyperemesis gravidarum, but its administration in the first trimester should be done with caution due to potential risks 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 use of ondansetron during pregnancy is not conclusively established as safe due to inconsistent findings and methodological limitations in epidemiological studies 2. Key points to consider include:

• Inconsistent findings in studies on the association between ondansetron use and major birth defects
• No identified risk of miscarriage or adverse maternal outcomes in postmarketing data
• Animal studies showed no evidence of harm to the fetus when ondansetron was administered during organogenesis However, due to the limitations and inconsistencies in the available data, caution is advised when considering the use of ondansetron during pregnancy.

From the Research

Zofran Use During Pregnancy

• The use of Zofran (ondansetron) during pregnancy has been studied in various research papers 3, 4, 5, 6, 7.
• According to a 2016 systematic review, ondansetron was found to be effective in reducing nausea and vomiting in pregnancy, especially for moderate symptoms 4.
• Another study published in 2004 found that ondansetron did not appear to increase the risk of major malformations above baseline 6.
• However, a 2021 assessment by the European Medicines Agency (EMA) and Pharmacovigilance Risk Assessment Committee (PRAC) concluded that ondansetron should not be used in the first trimester of pregnancy due to potential risks 5.
• A 2016 review highlighted the difficulties in interpreting the available data on ondansetron use during pregnancy and emphasized the need for practical guidelines regarding treatment of nausea and vomiting in pregnancy 7.

Safety and Efficacy

• The safety and efficacy of ondansetron during pregnancy have been evaluated in several studies, with some finding no significant increase in risk of birth defects or adverse pregnancy outcomes 4, 6.
• However, other studies have raised concerns about the potential risks of ondansetron use during pregnancy, particularly in the first trimester 5.
• The evidence on the use of ondansetron during pregnancy is limited, and more research is needed to fully understand its safety and efficacy 3, 7.

Clinical Guidelines

• Clinical guidelines for the treatment of nausea and vomiting in pregnancy recommend the use of ondansetron as a second-line treatment option for severe symptoms 4.
• However, the EMA and PRAC have updated the summary of product characteristics for ondansetron to state that it should not be used in the first trimester of pregnancy 5.
• Healthcare providers should carefully consider the potential risks and benefits of ondansetron use during pregnancy and follow practical guidelines for treatment of nausea and vomiting in pregnancy 7.