From the Guidelines
Ondansetron is generally considered safe for use during pregnancy when the benefits outweigh the risks, particularly for managing severe nausea and vomiting in pregnancy (NVP) or hyperemesis gravidarum. The typical dosage is 4-8 mg orally every 8 hours as needed, with a maximum daily dose of 24 mg. While ondansetron should not be used as a first-line treatment, it can be considered after other interventions like vitamin B6 and doxylamine have failed, as recommended by the American College of Obstetricians and Gynecologists (ACOG) 1.
Key Considerations
- Current evidence suggests no significant increase in overall birth defects with ondansetron use, though some studies have shown a small increased risk of oral clefts when used in the first trimester (approximately 3 additional cases per 10,000 births) 1.
- The medication works by blocking serotonin receptors in the chemoreceptor trigger zone and gastrointestinal tract, effectively reducing nausea and vomiting signals to the brain.
- Potential side effects include headache, constipation, and rarely QT interval prolongation.
- Patients with electrolyte abnormalities or heart conditions should use ondansetron with caution.
Decision Making
The decision to use ondansetron during pregnancy should be made after discussing the potential benefits and risks with a healthcare provider, considering the severity of symptoms and the impact on maternal health and nutrition. According to a recent study published in Gastroenterology, 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.
Safety Profile
Some studies have reported cases of congenital heart defects when ondansetron is given in the first trimester, but the risk is considered small, with a 0.03% absolute increase in orofacial and 0.3% in ventricular septal defects 1. Overall, the safety profile of ondansetron in pregnancy is considered favorable when used appropriately, and it can be a valuable option for managing severe NVP or hyperemesis gravidarum.
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 Ondansetron exposure in utero has not been associated with overall major congenital malformations in aggregate analyses
The safety of ondansetron (Zofran) in pregnancy is uncertain due to inconsistent findings and methodological limitations in epidemiological studies.
- Major birth defects: Studies have reported inconsistent findings, with some showing no association and others suggesting a possible increased risk of specific defects, such as cardiac septal defects or oral clefts.
- Miscarriage and adverse maternal outcomes: Available postmarketing data have not identified a drug-associated risk. Based on the available data, no conclusion can be drawn about the safety of ondansetron use in pregnancy 2.
From the Research
Safety of Ondansetron in Pregnancy
The safety of ondansetron in pregnancy has been a topic of debate, with various studies presenting different findings.
- A study published in 2021 3 discussed the updated assessment report on the use of ondansetron in the first trimester by the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC), which led to changes in the Summary of Product Characteristics (SmPC) stating that ondansetron should not be used in the first trimester of pregnancy.
- However, a systematic review of clinical trials published in 2023 4 found that ondansetron is an effective treatment for nausea and vomiting, including pregnancy-related morning sickness, but further research is needed to understand the potential risks and benefits associated with its use in pregnant women.
- A historical cohort study from Denmark published in 2013 5 found that ondansetron was not associated with a significantly increased risk of adverse fetal outcomes, including spontaneous abortion, stillbirth, major birth defects, preterm delivery, and low birth weight.
- In contrast, a study published in 2012 6 raised concerns about the safety of ondansetron during pregnancy, citing limited fetal safety data and a potential increased risk of cleft palate.
- Another study from Western Australia published in 2013 7 found no significant increase in major birth defects with first-trimester exposure to ondansetron, but the study was not conclusive about the safety of ondansetron in pregnancy.
Key Findings
- Ondansetron is effective in treating nausea and vomiting during pregnancy 4, 5.
- The European Medicines Agency (EMA) recommends avoiding ondansetron in the first trimester of pregnancy 3.
- Some studies suggest a potential increased risk of birth defects, such as cleft palate, with ondansetron use during pregnancy 6.
- Other studies found no significant increase in adverse fetal outcomes with ondansetron use 5, 7.