Is Zofran (ondansetron) safe to use in pregnant patients?

Safety of Ondansetron (Zofran) Use During Pregnancy

Ondansetron should be used as a second-line therapy for nausea and vomiting in pregnancy, only after first-line options have failed, due to potential concerns about congenital heart defects when used in the first trimester. 1

First-Line Treatment Options for Nausea and Vomiting in Pregnancy

• Vitamin B6 (pyridoxine) supplementation is recommended as the first-line treatment for hyperemesis gravidarum (HG) or severe nausea and vomiting in pregnancy 1, 2
• Doxylamine and pyridoxine combination is also considered a first-line option according to European guidelines 2
• For patients requiring additional medication, metoclopramide can be given as a second-line option with no reported increased risk of congenital defects 1

Ondansetron Use in Pregnancy

• Ondansetron should primarily be used in severe nausea and vomiting that requires hospitalization, and only as a second-line therapy 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
• Recent studies have reported inconsistent findings regarding ondansetron and congenital malformations, with some studies showing potential associations with congenital heart defects when given in the first trimester 1, 3
• The FDA drug label states that "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" 3

Evidence on Safety

• A large Danish cohort study found that ondansetron was not associated with significantly increased risk of spontaneous abortion, stillbirth, major birth defects, preterm delivery, or low birth weight 4
• However, a case-control study identified a modest association between prenatal exposure to ondansetron and cleft palate (adjusted OR 1.6,95% CI 1.1-2.3) 5
• Another study found no increased risk of miscarriage among women prescribed ondansetron versus alternative antiemetics during the first 20 weeks of pregnancy 6
• The prevalence of ondansetron use during pregnancy has increased significantly, from less than 1% before 2000 to 13% by 2013-2014 5, with 40% of prescriptions being initiated during the first trimester 7

Treatment Algorithm for Nausea and Vomiting in Pregnancy

1. Start with vitamin B6 (pyridoxine) supplementation as first-line therapy 1, 2
2. If inadequate response, add doxylamine (combination with pyridoxine) 2
3. For persistent symptoms, consider metoclopramide as a second-line option 1
4. Reserve ondansetron for severe cases not responding to first and second-line therapies, particularly after the first trimester when possible 1, 2
5. For severe cases requiring hospitalization, intravenous hydration and replacement of electrolytes, vitamins, and nutrients may be necessary 1

Important Considerations and Caveats

• The risk-benefit assessment should weigh the potential fetal risks against the maternal risks of untreated severe nausea and vomiting, including dehydration, electrolyte imbalances, and nutritional deficiencies 1
• If ondansetron is deemed necessary, it should be used at the lowest effective dose for the shortest duration possible 3
• Patients with severe symptoms may require a multidisciplinary approach involving obstetricians, nutritionists, psychologists, and gastroenterologists 1
• Thiamine (vitamin B1) supplementation should be considered in severe cases to prevent Wernicke encephalopathy, starting at 100 mg daily for at least 7 days 1