Fluconazole

Pregnancy

Miscarriage: In a Danish registry cohort (Mølgaard-Nielsen et al. 2016; 1,405,663 pregnancies), filled oral-fluconazole prescriptions from weeks 7 to 22 were associated with spontaneous abortion compared with matched unexposed pregnancies (HR 1.48, 95% CI 1.23 to 1.77); the topical-azole comparison also showed an association. A Quebec nested case-control study (Bérard et al. 2019; 441,949 pregnancies) found an association for cumulative doses of 150 mg or less and for doses over 150 mg, while no association with stillbirth was found. These are observational prescription-record studies, so they cannot establish causation or confirm ingestion. Birth defects: A Danish cohort (Mølgaard-Nielsen et al. 2013; 7,352 exposed pregnancies) found no increased overall birth-defect risk but observed a tetralogy-of-Fallot signal based on seven exposed cases. Bérard et al. found no increase in overall major malformations, but high first-trimester doses were associated with cardiac septal closure anomalies in 13 exposed cases. A large US Medicaid cohort (Zhu et al. 2020; 1,969,954 pregnancies, 37,650 exposed) found an adjusted association with musculoskeletal malformations, with an adjusted risk difference of about 12 per 10,000 exposed pregnancies; it did not find increased adjusted risks for conotruncal malformations or oral clefts overall. The study was limited to live births, used dispensing records, and notes residual confounding and small numbers for rare subtypes. A 2024 meta-analysis of nine observational studies (3,764,897 pregnancies, 116,425 exposed) found no significant association with overall major malformations in adjusted estimates, but did find an association with miscarriage; the authors note possible dose-related uncertainty. High-dose case reports describe a distinct pattern after prolonged exposure, and the FDA's 2011 communication concerned chronic high doses in the first trimester. The 2016 FDA notice was an interim review, not a final conclusion. The 2019 FDA statement was limited to miscarriage or stillbirth after one 150 mg dose. An FDA-hosted 2023 DIFLUCAN label says effective contraception should be considered for women of child-bearing potential treated with 400 to 800 mg/day throughout treatment and for about one week after the final dose; this is a dose-specific label consideration, not a formal pregnancy-prevention program. Current US CDC guidance, the 2023 EMA assessment, and the Pfizer label retain broader pregnancy cautions.

Breastfeeding

LactMed reports low milk levels after a single 150 mg dose and after repeated 200 mg daily dosing in small pharmacokinetic reports, and estimates that an exclusively breastfed infant exposed through milk during maternal 200 mg daily dosing would receive about 0.6 mg/kg daily. The Pfizer label describes a single-dose milk-level study in 10 breastfeeding women and estimates an infant dose of about 13% of the pediatric maintenance dose; it states that milk-level data after repeated or high-dose use are unavailable. In the prospective Moorhead et al. study (2011; 96 breastfeeding women treated for breast and nipple thrush), women used one to 29 150 mg capsules on alternate days, and the abstract reports only minor side effects. LactMed states that seven of the 96 women reported possible infant effects, including flushed cheeks, gastrointestinal upset, and runny or mucous stools. The Pfizer label reports no serious infant reactions in the survey. These data do not establish that fluconazole caused the reported symptoms and provide limited information for high-dose or prolonged maternal use.

What was tested

Pregnancy evidence includes observational prescription and registry studies, birth-outcome cohorts, case reports of prolonged high-dose exposure, and a 2024 systematic review and meta-analysis. These studies assess miscarriage, stillbirth, and congenital malformations, but cannot fully control confounding or confirm that every dispensed prescription was taken. The breastfeeding evidence includes small human milk-level measurements, one prospective 96-woman treatment survey, and clinical summaries. There are no adequate, well-controlled pregnancy trials, and the label reports no milk-level data after repeated or high-dose maternal use.