What is the recommended dosage and safety of Zofran (ondansetron) for pregnant women experiencing severe nausea and vomiting?

From the Guidelines

Ondansetron (Zofran) is recommended at a dosage of 4-8 mg orally every 8 hours as needed for pregnant women with severe nausea and vomiting, particularly when first-line treatments have failed, with the goal of using the lowest effective dose for the shortest duration necessary. This recommendation is based on the most recent and highest quality study available, which suggests that ondansetron is safe for use during pregnancy, with no significantly increased risk of major congenital defects, although a small potential increased risk of oral clefts has been reported when used in the first trimester 1. 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 cases that require hospitalization 1. It is essential for pregnant women to consult with their healthcare provider before starting ondansetron, as individual risk factors need to be considered. Treatment typically begins with other interventions like dietary modifications, vitamin B6, and doxylamine before considering ondansetron. Patients should be aware of potential side effects, including headache, constipation, and rarely, heart rhythm abnormalities, particularly in those with electrolyte abnormalities or heart conditions. The use of ondansetron in pregnancy has been associated with an increased rate of orofacial clefting, but the absolute risk is small, increasing from 11 cases per 10,000 births to 14 cases per 10,000 births 1.

Some key points to consider when prescribing ondansetron to pregnant women include:

• The medication should be used at the lowest effective dose for the shortest duration necessary
• Patients should be aware of potential side effects, including headache, constipation, and heart rhythm abnormalities
• Treatment typically begins with other interventions like dietary modifications, vitamin B6, and doxylamine before considering ondansetron
• The use of ondansetron in pregnancy has been associated with a small potential increased risk of oral clefts when used in the first trimester
• Pregnant women should always consult with their healthcare provider before starting ondansetron, as individual risk factors need to be considered.

Overall, the benefits of ondansetron in managing severe nausea and vomiting in pregnant women appear to outweigh the risks, and it is a commonly used medication in this population 1. However, it is crucial to carefully evaluate each patient's individual risk factors and medical history before prescribing ondansetron.

From the Research

Zofran and Pregnancy

• Zofran, also known as ondansetron, is a medication used to treat nausea and vomiting caused by cancer chemotherapy, but it is also prescribed off-label for nausea and vomiting during pregnancy (NVP) 2.
• The safety and effectiveness of ondansetron for NVP have been studied, with some studies suggesting that it may be effective, but safety data are insufficient to recommend it as a first-line agent 3.
• A study published in 2022 found that ondansetron is increasingly used off-label to treat NVP during pregnancy, with the most common oral daily dosages being 4 mg/d, 8 mg/d, 12 mg/d, and between 16 and 24 mg/d 2.
• However, the European Medicines Agency has stated that ondansetron should not be used during the first trimester of pregnancy due to a potential increased risk of orofacial clefts and congenital heart defects 4.
• A prospective comparative study published in 2004 found that ondansetron does not appear to be associated with an increased risk for major malformations above baseline, but the sample size was limited 5.

Recommended Dosage

• The recommended dosage of ondansetron for NVP is not established, but common oral daily dosages range from 4 mg/d to 24 mg/d 2.
• It is essential to note that ondansetron is not approved for use during pregnancy, and its use should be discussed with a healthcare provider.

Safety

• The safety of ondansetron during pregnancy is still a topic of debate, with some studies suggesting a potential increased risk of birth defects 4.
• However, other studies have found that ondansetron does not appear to be associated with an increased risk for major malformations above baseline 5.
• Women with mental health disorders, asthma, and/or prescribed folic acid may be more likely to experience NVP and use antiemetics, including ondansetron 2.