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

From the Guidelines

Fluconazole should be avoided during pregnancy, especially at high doses or for extended periods, due to the potential risk of birth defects, particularly when used during the first trimester 1. When considering the use of fluconazole during pregnancy, it is essential to weigh the benefits against the potential risks. The evidence suggests that high doses (400 mg daily or more) of fluconazole, particularly when used during the first trimester, may be associated with birth defects, including congenital craniosynostosis and skeletal abnormalities 1.

Some key points to consider:

• The US Food and Drug Administration has issued a warning about the potential risks of fluconazole during pregnancy, particularly when used at high doses or for extended periods 1.
• Animal studies have shown that azole antifungals, including fluconazole, may be associated with abnormal embryogenesis, particularly when used during early gestation 1.
• Topical antifungal treatments, such as clotrimazole or miconazole creams, are generally considered safer alternatives during pregnancy due to their minimal systemic absorption.
• If a systemic antifungal is necessary for a serious infection, the healthcare provider should carefully weigh the benefits against the potential risks and consider alternative treatments, such as amphotericin-based regimens 1.

In terms of specific guidance, the following recommendations can be made:

• For single-dose treatment of vaginal yeast infections, a 150 mg dose of fluconazole is generally considered low-risk.
• For more severe or persistent infections, alternative treatments should be considered, and the healthcare provider should carefully monitor the patient for any potential adverse effects.
• Pregnant women with coccidioidomycosis should be managed according to the recommended guidelines, which suggest avoiding azole antifungals during the first trimester and considering amphotericin-based regimens instead 1.

From the FDA Drug Label

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 A few published case reports describe a pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400 to 800 mg/day) during most or all of the first trimester. Spontaneous abortions and congenital abnormalities have been suggested as potential risks associated with 150 mg of fluconazole as a single or repeated dose in the first trimester of pregnancy based on retrospective epidemiological studies.

Fluconazole use in pregnancy is not recommended unless the patient has a severe or potentially life-threatening fungal infection and the anticipated benefit outweighs the possible risk to the fetus. There is a potential risk of congenital anomalies and spontaneous abortions associated with fluconazole use during pregnancy, particularly with high doses or during the first trimester 2.

From the Research

Safety of Fluconazole During Pregnancy

• The safety of fluconazole during pregnancy has been studied in several research papers 3, 4, 5, 6, 7.
• According to a study published in 1998, fluconazole exhibits dose-dependent teratogenic effects, but it appears to be safe at lower doses (150 mg/day) 3.
• A Danish population-based cohort study published in 2008 found no overall increased risk of congenital malformations after exposure to short-course treatment with fluconazole in early pregnancy 4.
• However, a study published in 2019 found that use of oral fluconazole during early pregnancy was associated with an increased risk of spontaneous abortion, and exposure to a high dose during the first trimester was associated with an increased risk of cardiac septal closure anomalies 5.
• Another study published in 2016 found that use of oral fluconazole in pregnancy was associated with a statistically significant increased risk of spontaneous abortion compared with risk among unexposed women and women with topical azole exposure in pregnancy 7.
• A case report published in 1996 discussed a pregnant patient with Candida albicans sepsis who was treated with fluconazole and had a favorable outcome for both the mother and the baby 6.

Dosage and Risk

• The risk of congenital malformations and spontaneous abortion appears to be dose-dependent, with higher doses of fluconazole associated with increased risk 5, 7.
• Lower doses of fluconazole (150 mg/day) may be safer during pregnancy, but more research is needed to confirm this 3, 4.
• The American College of Obstetricians and Gynecologists (ACOG) and other organizations recommend cautious prescribing of fluconazole in pregnancy, especially at higher doses 7.

Clinical Implications

• Healthcare providers should carefully consider the benefits and risks of fluconazole treatment during pregnancy and discuss the potential risks with their patients 3, 4, 5, 6, 7.
• Alternative treatments, such as topical azole antifungals, may be preferred for pregnant women with vaginal candidiasis 7.
• More research is needed to fully understand the safety of fluconazole during pregnancy and to inform clinical decision-making 5, 7.