Is it safe to use oral fluconazole (antifungal medication) or oral itraconazole (antifungal medication) in pregnant women?

Oral Fluconazole and Itraconazole Use in Pregnancy

Oral fluconazole and itraconazole should be avoided during the first trimester of pregnancy due to teratogenic risks, but can be considered after the first trimester when the benefits outweigh risks, with amphotericin B being the preferred agent for serious fungal infections during early pregnancy. 1, 2

First Trimester: Avoid Oral Azoles

• Intravenous amphotericin B is the recommended antifungal for pregnant women during the first trimester when systemic antifungal therapy is required for serious fungal infections 1

• High-dose fluconazole (400-800 mg/day) during the first trimester is associated with a distinct pattern of congenital anomalies including brachycephaly, abnormal facies, cleft palate, femoral bowing, and congenital heart disease 2

• Even low-dose fluconazole (≤150 mg) during early pregnancy is associated with increased risk of spontaneous abortion (adjusted OR 2.23,95% CI 1.96-2.54) and cardiac septal closure anomalies 3, 4

• The FDA warns that fluconazole-associated birth defects have been reported with doses of 400-800 mg/day during most or all of the first trimester, and epidemiological studies suggest potential risks even with 150 mg single or repeated doses 2

• Itraconazole is teratogenic in animals at high doses, though human data are limited; it should be avoided during the first trimester 1

After First Trimester: Azoles Can Be Considered

• After the first trimester, oral azoles such as fluconazole or itraconazole can be prescribed when clinically indicated 1

• For coccidioidomycosis developing after the first trimester, fluconazole or itraconazole are acceptable options (strong recommendation, low evidence) 1

• For coccidioidal meningitis diagnosed after the first trimester, fluconazole or itraconazole can be prescribed 1

Clinical Decision Algorithm

For pregnant women requiring systemic antifungal therapy:

1. First trimester (weeks 1-13):

   • Use intravenous amphotericin B for serious infections 1
   • Alternative: Close monitoring without therapy for mild infections (weak recommendation) 1
   • Last resort: Azole therapy only after extensive patient education about teratogenic risks 1

2. Second and third trimesters (weeks 14-delivery):

   • Oral fluconazole or itraconazole can be used 1
   • Amphotericin B remains an option throughout pregnancy 1

3. For women already on azole therapy who become pregnant:

   • Stop azole immediately upon pregnancy recognition 1
   • Switch to amphotericin B during first trimester 1
   • Resume azole therapy after first trimester if needed 1

Important Caveats and Pitfalls

• The teratogenic risk is dose-dependent: Single low doses (150 mg) for vaginal candidiasis carry lower risk than chronic high-dose therapy, though recent meta-analyses show even low doses increase cardiac defect risk (OR 1.95% CI 1.18-3.21) 5, 3

• Topical azoles are preferred over oral agents when feasible for superficial infections during pregnancy 1

• Effective contraception should be used in women of childbearing potential receiving fluconazole 400-800 mg/day, continuing for approximately 1 week (5-6 half-lives) after the final dose 2

• For life-threatening fungal infections, the risk-benefit calculation may favor azole use even in the first trimester after thorough patient counseling, though this is a weak recommendation 1

• Amphotericin B, while safer for the fetus, can cause maternal renal dysfunction and hypokalemia; neonates born to mothers on amphotericin B should be evaluated for these complications 1