Antifungal Therapy in Pregnancy

First Trimester Considerations

The American College of Obstetricians and Gynecologists and the Infectious Diseases Society of America recommend intravenous amphotericin B as the preferred antifungal agent for serious fungal infections during the first trimester of pregnancy, due to the teratogenic risks associated with oral azoles 1, 2, 3
Itraconazole should be avoided during the first trimester due to its teratogenic potential in animals, although human data are limited, as recommended by the Centers for Disease Control and Prevention 4, 5

After the first trimester, oral azoles such as fluconazole or itraconazole can be prescribed when clinically indicated, with a strong recommendation and low evidence for their use in coccidioidomycosis, as suggested by the Infectious Diseases Society of America 1, 2, 3
For coccidioidal meningitis diagnosed after the first trimester, fluconazole or itraconazole can be prescribed, based on guidelines from the Infectious Diseases Society of America 1, 2

Topical azoles are preferred over oral agents when feasible for superficial infections during pregnancy, as recommended by the Centers for Disease Control and Prevention 4, 6
For life-threatening fungal infections, the risk-benefit calculation may favor azole use even in the first trimester after thorough patient counseling, although this is a weak recommendation, as suggested by the Infectious Diseases Society of America 1
Amphotericin B, while safer for the fetus, can cause maternal renal dysfunction and hypokalemia, and neonates born to mothers on amphotericin B should be evaluated for these complications, as recommended by the Centers for Disease Control and Prevention 4

The Infectious Diseases Society of America recommends azole antifungals, such as itraconazole, for second and third trimester treatment of active nonmeningeal coccidioidomycosis and meningitis, at a dose of 400 mg daily 7, 8
Azole antifungals, including itraconazole, are acceptable after the first trimester for conditions requiring systemic antifungal therapy, such as coccidioidomycosis and histoplasmosis 7, 9

Itraconazole can be used in the third trimester when clinically indicated for serious fungal infections, as the teratogenic risk is primarily confined to first-trimester exposure 7
Life-threatening or severe fungal infections, such as histoplasmosis, coccidioidomycosis, and blastomycosis, may require itraconazole treatment, as the benefit outweighs the risk 9, 10
Amphotericin B remains the preferred agent for serious systemic fungal infections throughout all trimesters, due to its extensive safety data and lack of reported teratogenesis 10

Women of childbearing age receiving itraconazole should use effective contraception during therapy and for 2 months after discontinuation, due to the drug's long half-life and tissue accumulation 10
Therapeutic drug monitoring is recommended to ensure adequate drug exposure, particularly given altered pharmacokinetics in pregnancy 10
Women should not breastfeed while receiving itraconazole, as it enters breast milk at low concentrations but may accumulate over time 7, 9