Fluconazole is a triazole antifungal commonly used in the treatment of candidiasis. Standard fluconazole therapy generally comprises a single 150mg oral dose. Fluconazole is not recommended for use during pregnancy. However, vaginal candidiasis is common in pregnancy, and as fluconazole is sometimes prescribed to treat candidiasis that has not responded to topical/intravaginal clotrimazole treatment, exposure during pregnancy is not uncommon.
Data on the outcomes of over 43,000 fluconazole-exposed pregnancies, the majority of which were exposed to a single 150mg oral dose, do not reliably indicate increased risks of malformation overall, cardiac malformation overall, or orofacial clefts. Some studies have identified increased risks of specific cardiac defects, including tetralogy of Fallot, hypoplastic left heart, and transposition of the great arteries. However, these findings still require confirmation in additional datasets. Should these anomalies be related to low dose fluconazole exposure in the first trimester, the absolute risk to the fetus is still likely to be very small (<0.5%).
An increased risk of miscarriage among women exposed to standard dose oral fluconazole in early pregnancy has also been observed. Considering the best quality evidence currently available, the absolute risk of miscarriage following standard dose fluconazole exposure in early pregnancy could be estimated at 15 to 30% in comparison with an expected background rate of 10 to 20%.
Other adverse pregnancy outcomes, including intrauterine death/stillbirth, premature delivery, low birth weight and neonatal death, have not been linked to standard dose fluconazole therapy.
No studies have evaluated whether neurodevelopmental outcomes are altered in infants exposed to fluconazole in utero.
Prolonged high dose fluconazole therapy (400-800 mg/day) during the first trimester has been linked to a distinctive pattern of birth defects. Because this type of exposure is rare and controlled or denominator-based data are lacking, the magnitude of risk following high dose exposure remains to be determined. There is no information regarding risks of other adverse pregnancy outcomes after prolonged exposure to high dose fluconazole.
Exposure to standard dose fluconazole at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
Where high dose fluconazole therapy is necessary, or has inadvertently occurred during the first trimester, patients should be counselled about the possibility of birth defects, and where pregnancy is ongoing, offered a detailed anomaly scan. Features which have been observed among malformed fetuses/infants exposed to high dose fluconazole have also been described in Antley-Bixler syndrome. As such, genetic investigation is recommended for all suspected cases of high dose fluconazole embryopathy to exclude the possibility of a genetic condition, as there may be a risk of recurrence in any future pregnancy.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.