Terbinafine use for fungal infections in pregnancy does not appear to be associated with an increased risk of fetal malformations or deaths, a large European study has found.
A registry-based cohort study of data from 1 650 649 pregnancies in Danish women found no association between oral and topical terbinafine exposure in pregnancy and the risk of major malformations and spontaneous abortion.
In the study, propensity matching was used to compare outcomes for 891 women who took oral terbinafine during pregnancy and 3174 topical terbinafine-exposed women with those of 40 650 unexposed pregnancies.
Terbinafine exposure was defined as at least one filled prescription during the first trimester for major malformations and before 22 completed gestational weeks for spontaneous abortion. Exposure also included 14 days prior to birth.
The risk of major malformations (prevalence odds ratios) was 1.01 for oral terbinafine-exposed vs unexposed pregnancies (absolute risk difference 0.04%). For topical terbinafine-exposed the risk was 1.08 (absolute risk difference 0.26%).
The risk of adverse outcomes for oral vs topical terbinafine-exposed pregnancies was 1.18 (absolute risk difference 0.59%)
For the risk of spontaneous abortion, the hazard ratios were 1.06, 1.04 and 1.19, respectively.
Writing in JAMA Dermatology, the study authors said there were few large scale studied of terbinafine safety in pregnancy and consequently the use of systemic terbinafine during pregnancy is currently not advised. Current guidelines state that topical terbinafine may be safely used during pregnancy based on the assumption of limited systemic absorption.
Although this was an observational study, its large size and use of the first data from real world use of terbinafine suggested it could be used to help inform clinicians, patients, and drug regulatory authorities regarding the fetal safety of terbinafine use in pregnancy when clinically indicated, they said
However an accompanying commentary said that while the study showed terbinafine to be relatively safe to use in pregnancy the continuing uncertainty means that should not be used without weighing up the risk benefit ratio.
Since terbinafine is often used as a long term treatment for cosmetic conditions such as onychomycosis, its use could be deferred until after pregnancy, the authors suggested.
“However, what if an infection, such as tinea capitis, is symptomatic and cannot be effectively treated topically? This situation changes the risk-benefit ratio and might prompt a clinician to initiate treatment during pregnancy,” they wrote.
They also warned that little was known about the safety of terbinafine in lactation, with about 4% of the drug dose being passed on from a breastfeeding mother to the infant.
“Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations,” wrote Dr Jenny Murase, of the Department of Dermatology, Palo Alto Foundation Medical Group.
“At the same time, it is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation.