Is fluconazole (an antifungal medication) safe to use during pregnancy?

Safety of Fluconazole During Pregnancy

Fluconazole should be avoided during pregnancy, particularly in the first trimester, due to increased risks of spontaneous abortion and congenital malformations. 1, 2

Risk Assessment by Trimester

First Trimester

• Avoid fluconazole completely during the first trimester due to association with:
  • Craniofacial ossification defects 1, 2
  • Thin wavy ribs and renal pelvis defects 1
  • Congenital heart disease, particularly cardiac septal closure anomalies 3, 4
  • Increased risk of spontaneous abortion (2-3 times higher risk compared to unexposed pregnancies) 3

Second and Third Trimesters

• Use of fluconazole during later trimesters should be carefully considered:
  • Only use when the benefit of continuous antifungal exposure clearly outweighs potential risks 1
  • Lower risk compared to first trimester exposure, but safety is not fully established 1

Dose Considerations

• Dose matters significantly:
  • High-dose fluconazole (>150 mg) carries greater risk of congenital malformations 2, 3
  • Single low-dose (150 mg) treatment may have lower risk but is still associated with increased risk of spontaneous abortion 3
  • The FDA has specifically warned about long-term, high-dose (400-800 mg/day) fluconazole use during the first trimester 1

Alternative Treatment Options

• For systemic or disseminated fungal infections during pregnancy:
  • Amphotericin B (AmB) or Liposomal Amphotericin B (LFAmB) are preferred treatments (FDA category B) 1
  • These agents have shown no evidence of risk in humans and are well distributed in umbilical cord serum, amniotic fluid, and placenta 1

Special Considerations

For Limited Fungal Infections

• For limited and stable pulmonary cryptococcosis or other non-severe fungal infections:
  • Consider deferring antifungal therapy until after delivery with close monitoring 1
  • For vaginal candidiasis, topical azoles are preferred over oral fluconazole 3

Breastfeeding

• Fluconazole is excreted in breast milk at concentrations similar to plasma 1
• The American Academy of Pediatrics has indicated that breastfeeding while receiving fluconazole is likely safe for the newborn 1

Contraception Recommendations

• Effective contraceptive measures should be recommended to women of childbearing potential who are taking fluconazole 1, 2
• Contraception should continue throughout treatment and for approximately 1 week (5-6 half-lives) after the final dose 2

Clinical Pitfalls to Avoid

• Do not underestimate risks with "single dose" therapy - even short courses during pregnancy carry risks 3
• Do not assume all antifungals carry equal risk - amphotericin B has better safety data in pregnancy than azoles 1
• Watch for post-partum complications - rapid reversal of pregnancy-related immunosuppression can lead to worsening of previously stable fungal infections 1
• Consider the indication carefully - for non-life-threatening fungal infections, the risks of fluconazole likely outweigh the benefits 1