Is Zofran (ondansetron) safe to use during pregnancy?

Ondansetron (Zofran) Use in Pregnancy

Ondansetron should not be used as a first-line treatment for nausea and vomiting in pregnancy, particularly during the first trimester, due to potential safety concerns. 1, 2

Safety Profile and Risks

• The FDA label indicates inconsistent findings regarding birth defects, with some studies showing potential concerns:

  • Some data suggests a possible association with cardiac septal defects (RR 2.05,95% CI 1.19,3.28) 2
  • One large retrospective cohort study showed increased risk of oral clefts with oral ondansetron prescribed in the first trimester (RR 1.24,95% CI 1.03,1.48) 2
  • However, other studies have not confirmed these associations 2

• The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) has recommended against using ondansetron in the first trimester 3

Recommended Treatment Approach for Nausea and Vomiting in Pregnancy

First-Line Options:

1. Vitamin B6 (pyridoxine) supplementation
2. Doxylamine-pyridoxine combination
3. Phenothiazines 1

Second-Line Options (only if first-line fails):

1. Metoclopramide (5-10mg orally every 6-8 hours)
2. Ondansetron (only after 10 weeks gestation and when benefits outweigh risks)
3. Methylprednisolone for severe hyperemesis gravidarum 1

Special Considerations for Hyperemesis Gravidarum

The American College of Obstetricians and Gynecologists (ACOG) recommends using ondansetron only on a case-by-case basis for persistent symptoms, preferably after 10 weeks of pregnancy 1. For hyperemesis gravidarum specifically, ondansetron is considered an acceptable anti-emetic agent 4.

Monitoring and Precautions

• If ondansetron must be used (after first-line treatments have failed):
  • Preferably avoid during the first trimester, especially during weeks 6-9 when palate formation occurs 2
  • Consider the severity of the mother's condition - severe dehydration and malnutrition from untreated hyperemesis gravidarum also pose significant risks to both mother and fetus 1

Conclusion on Clinical Decision-Making

When treating nausea and vomiting in pregnancy:

1. Start with first-line agents (vitamin B6, doxylamine-pyridoxine, phenothiazines)
2. If these fail, consider metoclopramide before ondansetron
3. Reserve ondansetron for cases where:
   • First-line treatments have failed
   • Patient is beyond 10 weeks gestation if possible
   • The benefits of treating severe symptoms outweigh potential risks

While some studies have not shown significant increases in major malformations 5, the most recent guidelines and FDA labeling suggest caution, particularly in the first trimester.