Is Ondansetron (Zofran) safe to use at 16 weeks of gestation?

From the Guidelines

Ondansetron (Zofran) is generally considered safe to use at 16 weeks of gestation for treating nausea and vomiting, as the critical period of organ development is largely complete by this time, reducing potential risks. The typical dose is 4-8 mg taken orally every 8 hours as needed for nausea 1. While earlier studies raised concerns about potential birth defects when used in the first trimester, more recent and larger studies, such as the 2024 study published in Gastroenterology, have been reassuring regarding its safety throughout pregnancy 1. Many obstetricians prescribe Zofran when other anti-nausea medications like vitamin B6 and doxylamine (Unisom) haven't provided adequate relief.

Some key points to consider when using ondansetron during pregnancy include:

• The American College of Obstetricians and Gynecologists (ACOG) recommends using ondansetron on a case-by-case basis in patients with persistent symptoms before 10 weeks of pregnancy 1.
• A Cochrane review and meta-analysis of 25 studies found no significant difference in efficacy among medications commonly administered for hyperemesis gravidarum (HG), including metoclopramide, ondansetron, and promethazine 1.
• The European Association for the Study of the Liver Clinical Practice Guidelines recommend doxylamine and pyridoxine and phenothiazines as first-line pharmacologic treatment of HG, and metoclopramide and ondansetron as second-line therapies 1.
• Common side effects of ondansetron may include headache, constipation, and drowsiness.
• It's always important to discuss any medication use during pregnancy with your healthcare provider, as they can evaluate your specific situation and help weigh the benefits of treating severe nausea against any potential risks 1.

From the FDA Drug Label

1. 1 Pregnancy Risk Summary 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 at 16 weeks of gestation is not directly addressed in the FDA drug label. However, based on the available data, no conclusive evidence of harm to the fetus has been reported. The label does mention that reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered during organogenesis. Nevertheless, due to the inconsistent findings and methodological limitations of the epidemiological studies, caution should be exercised when using ondansetron during pregnancy. 2

From the Research

Safety of Ondansetron at 16 Weeks of Gestation

• The safety of ondansetron during pregnancy has been a subject of debate, with some studies suggesting a potential increased risk of congenital cardiac malformations and oral cleft 3.
• However, other studies have found ondansetron to be safe and effective for use in pregnancy, including at 16 weeks of gestation 4, 5.
• A systematic review of clinical trials found that ondansetron is an effective treatment for nausea and vomiting, including pregnancy-related morning sickness, but further research is needed to better understand the potential risks and benefits associated with its use in pregnant women 5.
• Some older studies have raised concerns about the safety of ondansetron during pregnancy, citing a lack of fetal safety data and potential risks such as QT prolongation and torsade de pointes 6.
• Expert opinion suggests that while there are reassuring studies on the fetal safety of ondansetron, more studies are needed to quantify fetal risks, particularly for severe nausea and vomiting of pregnancy and hyperemesis gravidarum 7.

Guidelines for Use

• 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 3.
• However, other guidelines suggest that ondansetron can be used as a second-line antiemetic for nausea and vomiting of pregnancy, with careful consideration of the potential risks and benefits 4.
• Women should be informed about the potential risks and benefits of ondansetron use during pregnancy and closely monitored for any adverse effects 4, 7.