Is ondansetron (Zofran) safe to use during pregnancy?

Safety of Ondansetron (Zofran) During Pregnancy

Ondansetron should be used during pregnancy only as a second-line therapy for severe nausea and vomiting that requires hospitalization, after first-line treatments have failed. 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 or severe nausea and vomiting in pregnancy 2, 1
• Doxylamine and pyridoxine combination is considered another first-line option according to European guidelines 1
• Metoclopramide can be given as a second-line option with no reported increased risk of congenital defects 2

Ondansetron Use and Safety During Pregnancy

• The American College of Obstetricians and Gynecologists recommends using ondansetron on a case-by-case basis in patients with persistent symptoms before 10 weeks of pregnancy 2, 1
• FDA labeling for ondansetron states: "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
• Some studies have reported potential associations between ondansetron and cardiac septal defects or oral clefts, but findings have been inconsistent across studies 3
• A systematic review of epidemiological evidence found limited data linking prenatal exposure to ondansetron to an increased risk of congenital malformations 4
• A more recent study did not find a statistically significant association between ondansetron exposure and the risk of overall major congenital malformations 5
• No increased risk of miscarriage has been observed with ondansetron use compared to alternative antiemetics 6

Important Safety Considerations

• The FDA has issued warnings about potentially serious QT prolongation and torsade de pointes associated with ondansetron use 7
• Ondansetron is not labeled or FDA-approved for use in nausea and vomiting of pregnancy in either the United States or Canada 7
• Fetal safety data for ondansetron are based on fewer pregnancies compared to first-line treatments like doxylamine-pyridoxine 7

Treatment Algorithm for Nausea and Vomiting in Pregnancy

1. Start with vitamin B6 (pyridoxine) supplementation as first-line therapy 2, 1
2. Add doxylamine if vitamin B6 alone is insufficient 1
3. Consider metoclopramide as a second-line option if first-line therapy fails 2
4. Reserve ondansetron for severe cases that have failed previous therapies, particularly when hospitalization is required 2, 1
5. For severe cases requiring hospitalization, consider thiamine supplementation (100 mg daily for at least 7 days) to prevent Wernicke encephalopathy 2

Clinical Pearls and Caveats

• Risk-benefit assessment should weigh potential fetal risks against maternal risks of untreated severe nausea and vomiting, including dehydration, electrolyte imbalances, and nutritional deficiencies 1
• Severe cases may benefit from a multidisciplinary approach involving obstetricians, gastroenterologists, and other specialists 2, 1
• Ondansetron use has increased significantly in recent years despite limited safety data compared to first-line alternatives 7, 8
• The efficacy of ondansetron for nausea and vomiting in pregnancy has been demonstrated, but safety concerns remain an area of ongoing research 8