Fluconazole Pregnancy Category
Fluconazole is FDA Pregnancy Category C (now Category D for high doses), meaning it should be avoided during pregnancy—particularly in the first trimester—due to documented risks of spontaneous abortion and congenital malformations, with amphotericin B being the preferred alternative for systemic fungal infections requiring treatment during pregnancy. 1
FDA Classification and Risk Profile
The FDA drug label classifies fluconazole as having potential for fetal harm, stating that "use in pregnancy should be avoided except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the anticipated benefit outweighs the possible risk to the fetus" 1
Chronic high-dose fluconazole (400-800 mg/day) during the first trimester causes a specific pattern of birth defects known as "fluconazole embryopathy," which includes brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease 1, 2
Even low-dose fluconazole (single 150 mg dose) has been associated with increased risk of spontaneous abortion (adjusted OR 2.23,95% CI 1.96-2.54) and cardiac septal closure anomalies when used during the first trimester 3, 4
Guideline-Based Recommendations by Clinical Scenario
For Severe/Systemic Fungal Infections During Pregnancy
Amphotericin B or liposomal amphotericin B are the preferred treatments for disseminated and CNS fungal disease during pregnancy, classified as FDA category B with no evidence of risk in humans 5, 2
Amphotericin B can be used with or without flucytosine (also category C), though flucytosine use must be weighed against benefit versus risk 5
Fluconazole should only be started after delivery for consolidation/maintenance therapy 5
For First Trimester Exposures
Fluconazole exposure during the first trimester should be completely avoided due to the highest risk period for congenital malformations 5, 2
If a woman becomes pregnant while taking fluconazole, she should be informed of the potential hazard to the fetus and amphotericin B should be substituted for invasive or refractory infections 5, 1
For Second and Third Trimester Considerations
During the last 2 trimesters, fluconazole use must be judged against the need for continuous antifungal exposure during pregnancy, though amphotericin B remains preferred 5
For limited and stable pulmonary cryptococcosis or other non-severe fungal infections, defer fluconazole treatment until after delivery with close monitoring during pregnancy 5, 2
Contraceptive Counseling Requirements
- Effective contraceptive measures should be recommended to all women of childbearing potential taking fluconazole 400-800 mg/day, continuing throughout treatment and for approximately 1 week (5-6 half-lives) after the final dose 1, 2
Topical Alternatives for Vaginal Candidiasis
Topical azoles (clotrimazole, miconazole) are the preferred first-line treatment throughout pregnancy for vaginal candidiasis and are safe and effective 5, 2
Single-dose oral fluconazole (150 mg) for vaginal candidiasis, while commonly prescribed, carries increased risk and should be avoided in favor of topical alternatives 2
Postpartum and Breastfeeding Considerations
Fluconazole can be safely initiated after delivery for consolidation and maintenance therapy 5
Breastfeeding while receiving fluconazole is considered safe, as fluconazole is present in breast milk at levels less than neonatal dosing and is compatible with breastfeeding per the American Academy of Pediatrics 2, 6
Watch for immune reconstitution inflammatory syndrome (IRIS) in the postpartum period as pregnancy-related immunosuppression rapidly reverses 5
Critical Caveats
Neonates born to women on chronic amphotericin B at delivery should be evaluated for renal dysfunction and hypokalemia 5, 2
The distinction between pregnancy risk (avoid fluconazole) and lactation safety (fluconazole is safe) is critical and should not be confused 2, 6
Chemoprophylaxis with systemically absorbed azoles should not be initiated during pregnancy and should be discontinued in women who become pregnant 5, 2