Is ondansetron (Zofran) safe to use during pregnancy?

Safety of Ondansetron Use During Pregnancy

Ondansetron can be used during pregnancy as a second-line agent for nausea and vomiting, but should be used with caution in the first trimester due to a small increased risk of orofacial clefts (0.03%) and cardiovascular malformations, particularly ventricular septal defects (0.3%). 1, 2

Safety Profile and Risks

• Ondansetron has not been linked to a high risk of congenital defects overall, but studies have identified a marginal relative increase in specific birth defects when used in early pregnancy 1
• The FDA pregnancy data indicates inconsistent findings regarding major birth defects, with some studies showing no association while others suggest a possible link to cardiac septal defects and oral clefts 3
• The absolute risk increase is small: approximately 0.03% for orofacial clefts and 0.3% for ventricular septal defects 1, 2
• The European Medicines Agency (EMA) took a more conservative stance in 2019, stating ondansetron should not be used in the first trimester, though this decision has been criticized as insufficiently substantiated 4

Clinical Recommendations

• Ondansetron should be considered a second-line agent for pregnancy-related nausea and vomiting 1, 2
• First-line treatments should include:
  • Pyridoxine (vitamin B6) 10-25 mg every 8 hours 2
  • Metoclopramide 5-10 mg orally every 6-8 hours, which has been shown to be safe in pregnancy with no significant increase in major congenital defects 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

Treatment Algorithm for Nausea and Vomiting in Pregnancy

1. Start with dietary and lifestyle modifications 2
2. If insufficient, add pyridoxine (vitamin B6) as first-line pharmacological treatment 2
3. For persistent symptoms, consider metoclopramide as the preferred second-line agent 1, 2
4. Reserve ondansetron for cases where first-line treatments fail, particularly after 10 weeks gestation 1, 2
5. For severe hyperemesis gravidarum requiring hospitalization, IV hydration and replacement of electrolytes may be necessary 1

Special Considerations

• Ondansetron use has been increasing in pregnancy despite limited safety data, with prescription rates rising from 0.1% in 2005 to 2.5% in 2019 5
• Thiamine supplementation should be considered in cases of prolonged vomiting to prevent Wernicke encephalopathy 1, 2
• Methylprednisolone can be considered as a last resort for severe hyperemesis gravidarum, but should be avoided before 10 weeks gestation due to a small risk of cleft palate 1

Monitoring and Follow-up

• Pregnant patients receiving medications for nausea and vomiting, especially those receiving chemotherapy, need additional ultrasounds (every 3-4 weeks) to document adequate fetal growth 1
• For women with cancer receiving chemotherapy during pregnancy, fetal umbilical artery Doppler exams should be considered to evaluate for potential fetal anemia 1

While ondansetron can be effective for treating severe nausea and vomiting in pregnancy, its use should be carefully considered, especially in the first trimester, weighing the small potential risks against the benefits of symptom relief and prevention of complications from severe nausea and vomiting 2, 6, 7.