Oral, topical terbinafine use may be safe in pregnancy

Pregnancies exposed to oral or topical terbinafine had no increased risk for major malformations or spontaneous abortion compared with unexposed pregnancies, according to a study.

“Terbinafine is a widely used antifungal agent available in both oral and topical formulations, but data on the fetal safety of use of terbinafine in pregnancy are very limited,” study author Niklas Worm Andersson, MD, of the department of clinical pharmacology at Copenhagen University Hospital, Denmark, told Healio.

In a historical registry-based cohort study, risk for birth malformations and spontaneous abortions were investigated in Denmark from 1997 to 2016 using propensity score matching. Among a cohort of 1,650,649 pregnancies eligible for inclusion, 891 oral terbinafine-exposed pregnancies and 3,174 topical terbinafine-exposed pregnancies were identified. A total of 40,650 unexposed pregnancies were included for the propensity-matched outcome analyses.

Malformation analyses included 5,742 pregnancies for the comparison of oral exposure vs. no exposure and found infants diagnosed with major malformations occurred in 3.8% of exposed cases compared with 3.8% of unexposed cases. This corresponded to an absolute risk difference (ARD) of 0.04% (95% CI, –1.69% to 1.76%). Of the 16,236 pregnancies used for comparison of topical exposure vs. no exposure, major malformations occurred in 3.6% of infants exposed and 3.3% of infants who were not exposed, for an ARD of 0.26% (95% CI, –0.73% to 1.26%). In the comparison of 1,020 pregnancies for oral vs. topical terbinafine exposure, major malformations occurred in 3.9% of orally exposed infants and 3.3% of topically exposed infants, yielding an ARD of 0.59% (95% CI, –1.71% to 2.88%).

Spontaneous abortion analyses included 9,801 pregnancies for oral exposure vs. no exposure, occurring in 10.4% of exposed pregnancies and 10.3% of unexposed pregnancies, yielding an ARD of 0.13% (95% CI, –1.97% to 2.24%). Analysis of topical exposure vs. no exposure included 32,914 pregnancies and found 5.2% of exposed pregnancies resulted in spontaneous abortion compared with 5.1% of unexposed pregnancies. This yielded an ARD of 0.17% (95% CI, –0.64% to 0.98%). Of the 1,234 pregnancies analyzed for oral vs. topical terbinafine exposure, 10.7% of orally exposed pregnancies resulted in spontaneous abortion compared with 9.6% of topically exposed pregnancies, with an ARD of 1.13% (95% CI, –2.23% to 4.50%).

“Our study results were not suggestive of an increased risk of major malformations or spontaneous abortion among pregnancies exposed to oral or topical terbinafine,” Andersson said. “This is the first published observational study to examine the association between terbinafine use in pregnancy and fetal safety outcomes. Our results may provide reassurance for pregnancies exposed to terbinafine as well as help inform clinicians, patients and drug regulatory authorities.” – by Kate Burba

Disclosures: Andersson reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.