Is ondansetron (Zofran) safe to use during pregnancy?

Ondansetron Use During Pregnancy

Ondansetron can be used during pregnancy as a second-line treatment for nausea and vomiting, but should be used with caution in the first trimester due to a small but potential risk of cardiac malformations and oral clefts. 1, 2

Safety Profile

• Ondansetron has not been linked to a high risk of congenital defects overall, but studies have shown a marginal relative increase in cleft palate (0.03% absolute increase) and cardiovascular malformations, particularly ventricular septal defects (0.3% absolute increase) 1, 2
• FDA labeling notes that epidemiological studies on ondansetron use and major birth defects have reported inconsistent findings with important methodological limitations 3
• One large retrospective cohort study of 1,970 women who received ondansetron during pregnancy found no association with major congenital malformations, miscarriage, stillbirth, preterm delivery, or low birth weight infants 3
• Animal studies did not show evidence of harm to the fetus when ondansetron was administered during organogenesis at doses 6-24 times the maximum recommended human dose 3

Recommendations for Clinical Use

• Metoclopramide (5-10 mg orally every 6-8 hours) should be considered as first-line therapy for nausea and vomiting in pregnancy due to its established safety profile 1, 2
• 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, 2
• Ondansetron should be reserved as a second-line agent when first-line therapies (such as vitamin B6, doxylamine, or metoclopramide) are ineffective 1, 2
• For severe nausea and vomiting of pregnancy (hyperemesis gravidarum), a step-up approach is recommended, with ondansetron considered after failure of first-line therapies 1

Treatment Algorithm for Nausea and Vomiting in Pregnancy

1. First-line options:

   • Dietary and lifestyle modifications 2
   • Vitamin B6 (pyridoxine) 10-25 mg every 8 hours 2
   • Metoclopramide 5-10 mg orally every 6-8 hours 1, 2

2. Second-line options (if first-line therapy fails):

   • Ondansetron 8 mg every 4-6 hours as needed 1, 2
   • Consider baseline ECG before starting ondansetron due to risk of QT prolongation 1

3. For severe, refractory cases:

   • Methylprednisolone (after 10 weeks gestation) 1
   • Consider hospitalization for IV hydration and electrolyte replacement 1

Important Considerations and Monitoring

• Ondansetron use has increased significantly worldwide despite limited pregnancy safety data 4, 5
• Monitor for potential side effects including headache and QT interval prolongation 1, 3
• Thiamine supplementation should be considered in cases of prolonged vomiting to prevent Wernicke encephalopathy 1, 2
• Women with mental health disorders, asthma, and those prescribed folic acid appear more likely to experience nausea and vomiting in pregnancy and use antiemetics 5

Clinical Perspective

• Despite concerns, many experts believe the benefits of treating severe nausea and vomiting in pregnancy may outweigh the small potential risks of ondansetron 6
• The European Network of Teratology Information Services has argued against overly restrictive regulatory decisions limiting ondansetron use in pregnancy 7
• Early treatment of nausea and vomiting is recommended to prevent progression to hyperemesis gravidarum, which carries significant maternal and fetal risks 1, 6