Is fluconazole (Diflucan) safe during pregnancy?

Is Diflucan (Fluconazole) Safe During Pregnancy?

Fluconazole should be avoided during pregnancy, particularly in the first trimester, due to documented risks of birth defects and spontaneous abortion, with topical antifungal agents being the preferred alternative for most fungal infections. 1, 2

Risk Profile by Dose and Trimester

High-Dose Fluconazole (≥400 mg daily)

• Chronic high-dose fluconazole (400-800 mg/day) causes a specific pattern of birth defects known as "fluconazole embryopathy," which includes craniosynostosis, characteristic facial features, digital synostosis, limb contractures, cleft palate, and skeletal abnormalities. 3, 4, 2
• Four documented cases of infants born with craniofacial and skeletal abnormalities following prolonged in utero exposure to high-dose fluconazole have been reported. 3, 5

Low-Dose Fluconazole (150-300 mg)

• Single-dose or episodic low-dose fluconazole (150 mg) has been associated with increased risk of spontaneous abortion and congenital abnormalities in epidemiological studies, though these findings have limitations and have not been confirmed in controlled trials. 1, 2
• A large Danish registry study of 7,352 fluconazole-exposed pregnancies (mostly 150-300 mg doses) found no increased risk of birth defects overall, but did identify a significantly increased risk of tetralogy of Fallot (adjusted prevalence odds ratio 3.16,95% CI 1.49-6.71). 6

Recommended Alternatives by Clinical Scenario

For Vaginal Candidiasis

• Topical azoles (clotrimazole, miconazole) are the preferred first-line treatment throughout pregnancy and are safe and effective. 3, 4, 1
• Oral fluconazole should not be used for vaginal candidiasis during pregnancy. 3, 5

For Oral Candidiasis (Thrush)

• Clotrimazole troches (10 mg 5 times daily for 7-14 days) are recommended as first-line therapy, especially in the first trimester. 4
• Nystatin suspension is an acceptable alternative topical option. 4

For Severe or Refractory Fungal Infections

• Amphotericin B (intravenous, 0.3 mg/kg daily) is the safest systemic antifungal option during pregnancy and is classified as FDA category B. 3, 4, 1
• Substitution of amphotericin B for high-dose fluconazole in the first trimester is specifically recommended for invasive or refractory esophageal candidal infections. 3
• Neonates born to women on chronic amphotericin B at delivery should be evaluated for renal dysfunction and hypokalemia. 3, 4

Management of Women Already on Fluconazole

Primary or Secondary Prophylaxis

• Chemoprophylaxis with systemically absorbed azoles should not be initiated during pregnancy and should be discontinued in HIV-infected women who become pregnant. 3, 5
• For women on secondary prophylaxis (chronic maintenance therapy) for cryptococcosis who become pregnant, therapy with amphotericin B may be preferred, especially during the first trimester. 3

Contraception Counseling

• Effective birth control 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

Common Pitfalls to Avoid

• Do not prescribe oral fluconazole for simple vaginal or oral candidiasis during pregnancy when topical alternatives are available and effective. 4, 5
• Do not assume that low-dose fluconazole is completely safe based on older studies; recent epidemiological data suggest potential risks even at 150 mg doses. 1, 2, 6
• Do not continue azole prophylaxis in HIV-infected women who become pregnant; the risks outweigh benefits given the low incidence of opportunistic fungal infections and availability of effective treatment for acute disease. 3

Special Considerations

Second and Third Trimester

• If topical therapy fails after the first trimester, oral fluconazole may be considered with extreme caution and only if benefits clearly outweigh risks, but this should be reserved for severe cases with infectious disease consultation. 3, 4

Breastfeeding

• Fluconazole is excreted in breast milk at low levels, and breastfeeding while receiving fluconazole is likely safe for the newborn according to available data. 1