Is Zofran (ondansetron) safe to use in the 3rd trimester of pregnancy?

From the Guidelines

Zofran (ondansetron) is considered safe to use in the 3rd trimester of pregnancy, with the benefits outweighing the risks, as indicated by recent guidelines and studies 1. When considering the use of Zofran in the 3rd trimester, it's essential to weigh the potential benefits against the risks. The medication is commonly prescribed for severe nausea and vomiting in pregnancy that hasn't responded to other treatments.

• The typical dose is 4-8 mg taken orally every 8 hours as needed, with a maximum daily dose of 24 mg.
• While earlier concerns existed about potential birth defects when used in the first trimester, most recent research suggests minimal risks in the third trimester.
• Some healthcare providers may recommend monitoring for potential side effects such as QT interval prolongation (a heart rhythm issue) in both mother and baby.
• Ondansetron works by blocking serotonin receptors in the brain and gut that trigger nausea and vomiting.
• As with any medication during pregnancy, it should only be used under medical supervision, and the lowest effective dose should be used for the shortest duration necessary to control symptoms.
• Alternative treatments like vitamin B6, ginger, or other anti-nausea medications might be considered first before using Zofran, depending on symptom severity. According to the EASL clinical practice guidelines on the management of liver diseases in pregnancy 1, ondansetron is listed as a second-line recommended treatment for management of Hyperemesis Gravidarum, with a compatible use in the 2nd/3rd trimester.
• Additionally, the ESMO expert consensus statements on the management of breast cancer during pregnancy also support the use of ondansetron during pregnancy, considering it safe when the benefits outweigh the risks 1. It's crucial to note that the use of ondansetron in early pregnancy has been associated with a marginal relative increase in cleft palate and cardiovascular malformations, but this risk is small, with an absolute increase of 0.03% in orofacial and 0.3% in ventricular septal defects 1.
• However, in the context of the 3rd trimester, the benefits of using ondansetron to manage severe nausea and vomiting often outweigh the risks, and it is considered a safe option under medical supervision.

From the FDA Drug Label

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 Ondansetron exposure in utero has not been associated with overall major congenital malformations in aggregate analyses

The use of Zofran (ondansetron) in the 3rd trimester of pregnancy is not directly addressed in the provided drug label. However, available data suggest that ondansetron exposure in utero has not been associated with overall major congenital malformations in aggregate analyses.

• Key points:
  • No drug-associated risk of miscarriage or adverse maternal outcomes was identified.
  • Reproductive studies in rats and rabbits showed no evidence of harm to the fetus.
  • Ondansetron exposure in utero was not associated with overall major congenital malformations. However, due to the lack of direct information regarding the 3rd trimester, caution should be exercised when considering the use of ondansetron during this period 2.

From the Research

Safety of Zofran in the 3rd Trimester of Pregnancy

• The safety of Zofran (ondansetron) in the 3rd trimester of pregnancy is a topic of ongoing debate and research 3, 4, 5, 6, 7.
• Some studies suggest that ondansetron is effective in controlling severe vomiting in pregnancy, with one study finding that it had a more favorable effect in controlling severe vomiting compared to metoclopramide 4.
• However, other studies have raised concerns about the potential risks of ondansetron use during pregnancy, including an increased risk of cleft palate and QT prolongation 5, 6.
• The European Medicines Agency (EMA) has updated its guidance on the use of ondansetron in pregnancy, stating that it should not be used in the first trimester due to the potential risks 5.
• However, the evidence for the safety of ondansetron in the 3rd trimester is limited, and more research is needed to fully understand its effects 3, 7.
• A study comparing the effectiveness of different antiemetics in an emergency department setting found that ondansetron was associated with similar mean time from administration to disposition as other antiemetics 7.

Key Findings

• Ondansetron is effective in controlling severe vomiting in pregnancy 4.
• The EMA has updated its guidance on the use of ondansetron in pregnancy, stating that it should not be used in the first trimester due to the potential risks 5.
• The evidence for the safety of ondansetron in the 3rd trimester is limited, and more research is needed to fully understand its effects 3, 7.
• Ondansetron is associated with similar mean time from administration to disposition as other antiemetics in an emergency department setting 7.

Study Limitations

• The studies had small sample sizes and limited follow-up periods 3, 4, 6.
• The evidence for the safety of ondansetron in the 3rd trimester is limited, and more research is needed to fully understand its effects 3, 7.
• The studies had varying methodologies and outcomes, making it difficult to compare results 3, 4, 5, 6, 7.