Is Diflucan (fluconazole) safe to use during pregnancy?

Fluconazole (Diflucan) in Pregnancy: Safety Considerations

Fluconazole should not be used during pregnancy, especially in the first trimester, due to potential risks of birth defects. Topical antifungal treatments are preferred for vaginal candidiasis in pregnant women. 1, 2, 3

Risk Assessment of Fluconazole in Pregnancy

First Trimester Risks

• High-dose fluconazole (≥400 mg daily) has been associated with a pattern of birth defects known as "fluconazole embryopathy" including:
  • Craniosynostosis
  • Characteristic facial abnormalities
  • Digital synostosis
  • Limb contractures 1, 3
• Even lower doses may pose risks:
  • A meta-analysis found increased prevalence of heart defects with both low-dose and any-dose fluconazole exposure during first trimester 4
  • Specifically, increased risk of tetralogy of Fallot has been observed 5

Later Pregnancy Considerations

• While single-dose (150 mg) episodic treatment has not shown consistent association with birth defects in some studies 1, more recent evidence suggests caution is warranted throughout pregnancy 4
• The FDA classifies fluconazole as Pregnancy Category C for single-dose treatment of vaginal candidiasis but Category D for higher doses or prolonged use 2, 3

Alternative Treatment Approaches for Pregnant Women

Recommended Treatments for Vaginal Candidiasis

• First-line therapy: Topical azole antifungals are preferred during pregnancy 1, 2
  • These include clotrimazole, miconazole, or other topical preparations
  • Topical treatments have minimal systemic absorption and are considered safer

For Systemic or Severe Fungal Infections

• For invasive or refractory fungal infections requiring systemic therapy, amphotericin B formulations are recommended instead of fluconazole, especially in the first trimester 1
• Neonates born to women on amphotericin B should be evaluated for renal dysfunction and hypokalemia 1

Special Considerations

Contraception Recommendations

• Women of childbearing potential taking fluconazole should use effective contraception during treatment and for approximately one week after the final dose 2, 3
• If a woman becomes pregnant while taking fluconazole, she should be informed of the potential risks to the fetus 3

Breastfeeding Considerations

• Fluconazole is present in breast milk at concentrations similar to plasma levels 1, 3
• Caution should be exercised when administering fluconazole to nursing women 2

Clinical Decision Algorithm

1. Confirm diagnosis of fungal infection requiring treatment
2. Determine pregnancy status before prescribing fluconazole
3. If patient is pregnant:
   • For vaginal candidiasis: Use topical azole antifungals instead of oral fluconazole
   • For systemic infections: Consider amphotericin B formulations if treatment is essential
4. If patient is of childbearing potential:
   • Verify effective contraception before prescribing fluconazole
   • Inform about risks and need to continue contraception for one week after treatment

The evidence clearly demonstrates that the risks of fluconazole in pregnancy, particularly regarding birth defects, outweigh potential benefits for most fungal infections, and safer alternatives are available.