USE OF FLUCONAZOLE IN PREGNANCY

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(Date of issue: May 2016, Version: 2.2)

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.

A corresponding patient information leaflet on fluconazole use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

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 clotrimazole treatment, exposure during pregnancy is not uncommon. Where fluconazole use is considered necessary in pregnancy, the risks and benefits of treatment should be discussed with the patient to support evidence-based shared decision making.

Data on the outcomes of over 8,000 fluconazole-exposed pregnancies, the majority of which were exposed to a 150mg single oral dose, show no increase in the incidence of overall malformation rate. One case-control and a large cohort study have reported a significant association between conotruncal defects and in utero exposure to standard doses of fluconazole during the first trimester, however the absolute risk to the fetus is still likely to be very small (<0.1%). An increased risk of spontaneous abortion following maternal exposure to fluconazole has been reported in a recent large study, but a causal association remains to be confirmed. Rates of stillbirth, prematurity and low birth weight infants have not been shown to be elevated in standard dose fluconazole-exposed pregnancies. No studies have evaluated whether neurodevelopmental outcomes are altered in infants exposed to fluconazole in utero.

Fluconazole is also used on a continuous basis at higher doses (~400-800mg/day) for serious mycotic infections.  This type of exposure is unusual during pregnancy, and consequently no large-scale studies of pregnancy outcomes have been carried out.  However, case reports of five pregnancies suggest that high dose chronic fluconazole therapy during the first trimester is teratogenic and is associated with a distinct and consistent pattern of malformations.  Because exposure in pregnancy to fluconazole at these doses is uncommon and the number of reported cases is low, the magnitude of individual fetal risk following exposure to high dose fluconazole remains to be established.  Additionally, since these case studies all involved prolonged exposure to fluconazole, it is also not known whether acute exposure to a single high dose of fluconazole carries a risk of teratogenesis.

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.

Fluconazole has a relatively long plasma elimination half-life (~ 30 hours) in the non-pregnant patient and has been shown to accumulate in some tissues.  There are no official guidelines on how long women who have been on high dose fluconazole therapy should wait before attempting to conceive.

Genetic investigation of a child or fetus with congenital malformations following fluconazole exposure in utero  is strongly recommended to exclude the possibility of co-occurrence of a genetic syndrome for which there is a risk of recurrence in future pregnancies.
               
This document is regularly reviewed and updated. Only use full UKTIS monographs downloaded directly from TOXBASE.org to be sure you are using the most up-to-date version. The summaries of these monographs are openly available on UKTIS.org.

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 health care professionals at www.toxbase.org.

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.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to ensure you are using the most up-to-date version.