Fluconazole Dosing in Pregnant Women
Fluconazole should not be initiated during pregnancy due to potential teratogenic effects, particularly during the first trimester, and should be discontinued in women who become pregnant while on therapy. 1
Risk Assessment
Systemic azole antifungals, including fluconazole, have been associated with significant risks during pregnancy:
- Four cases of infants born with craniofacial and skeletal abnormalities following prolonged in utero exposure to fluconazole have been documented 1
- High-dose fluconazole (400-800 mg/day) during the first trimester has been linked to a pattern of birth defects called "fluconazole embryopathy" 1
- A meta-analysis found that maternal exposure to fluconazole during the first trimester correlates with increased prevalence of heart defects in offspring, even at low doses (OR 1.95% CI 1.18-3.21) 2
- Fluconazole use during pregnancy has been associated with increased risk of spontaneous abortion (HR 1.48; 95% CI, 1.23-1.77) 3
Recommendations Based on Trimester
First Trimester
- Do not initiate fluconazole therapy 1
- For women who conceive while on fluconazole prophylaxis and elect to continue pregnancy, discontinue fluconazole immediately 1
- For cases requiring systemic antifungal treatment (such as invasive fungal infections):
- Intravenous amphotericin B is the recommended alternative 1
Second and Third Trimesters
- While guidelines suggest lower risk after the first trimester, caution is still warranted
- For women with cryptococcal meningitis, amphotericin B (with or without flucytosine) is recommended 1
- For women with limited and stable pulmonary cryptococcosis, close follow-up is recommended with fluconazole administration postponed until after delivery 1
Special Considerations
For HIV-Infected Pregnant Women
- Chemoprophylaxis against oropharyngeal, esophageal, or vaginal candidiasis using systemically absorbed azoles should not be initiated during pregnancy 1
- For women already on azole therapy who become pregnant, discontinue therapy 1
- For cryptococcal disease requiring treatment during pregnancy, amphotericin B is preferred, especially during the first trimester 1
For Coccidioidomycosis During Pregnancy
- For women who develop initial non-meningeal coccidioidal infection during the first trimester, intravenous amphotericin B is recommended 1
- After the first trimester, fluconazole or itraconazole may be considered 1
Alternative Treatments
- For vaginal candidiasis: Topical therapy is preferred during pregnancy 1
- For systemic fungal infections requiring treatment: Amphotericin B has the most pregnancy experience with no reports of teratogenesis 4
Important Caveats
- Effective birth control measures should be recommended to all women on azole therapy 1
- Monitor for immune reconstitution inflammatory syndrome (IRIS) in the postpartum period in women with cryptococcosis 1
- Neonates born to women on chronic amphotericin B at delivery should be evaluated for renal dysfunction and hypokalemia 1
While some studies suggest that short-course, low-dose fluconazole (150 mg) may not significantly increase overall malformation risk 5, 6, the most recent and comprehensive evidence indicates potential risks. Given the availability of safer alternatives, fluconazole should be avoided during pregnancy whenever possible.