Evaluation of Association Between Oral and Topical Terbinafine Use in Pregnancy and Risk of Major Malformations and Spontaneous Abortion

Importance Terbinafine is a commonly used antifungal agent, but safety data of its use in pregnancy are limited. Objective To examine the association between oral and topical terbinafine exposure in pregnancy and the risk of major malformations and spontaneous abortion. Design, Setting, and Participants A nationwide, registry-based cohort study was conducted in Denmark from January 1, 1997, to December 31, 2016, in a cohort of 1;650;649 pregnancies. Data analysis was performed from July 11 to October 20, 2019. Pregnancies were matched on propensity scores comparing oral terbinafine exposed vs unexposed (1:10 ratio), topical terbinafine exposed vs unexposed (1:10), and oral vs topical terbinafine exposed (1:1). Exposures Filled prescriptions for oral or topical terbinafine. Main Outcomes and Measures Logistic regression was used to compute prevalence odds ratios for the primary outcome of major malformations and Cox proportional hazards regression was used to compute hazard ratios for the secondary outcome of spontaneous abortion. Results Based on a cohort of 1;650;649 pregnancies, oral terbinafine-exposed (n = 891 pregnancies; mean [SD] age, 30.4 [6] years) and topical terbinafine-exposed (n = 3174; mean [SD] age, 29.5 [5.4] years) pregnancies were identified; up to a total of 40 650 unexposed pregnancies were included for the matched outcome analyses. In propensity-matched comparisons of the risk of major malformations, the prevalence odds ratios were 1.01 (95% CI, 0.63-1.62) for oral terbinafine-exposed vs unexposed pregnancies (absolute risk difference [ARD], 0.04%; 95% CI, -1.69% to 1.76%), 1.08 (95% CI, 0.81-1.44) for topical terbinafine-exposed vs unexposed pregnancies (ARD, 0.26%; 95% CI, -0.73% to 1.26%), and 1.18 (95% CI, 0.61-2.29) for oral vs topical terbinafine-exposed pregnancies (ARD, 0.59%; 95% CI, -1.71% to 2.88%). For the risk of spontaneous abortion, the hazard ratios were 1.06 (95% CI, 0.86-1.32) for oral terbinafine-exposed vs unexposed pregnancies (ARD, 0.13%; 95% CI, -1.97% to 2.24%), 1.04 (95% CI, 0.88-1.21) for topical terbinafine-exposed vs unexposed pregnancies (ARD, 0.17%; 95% CI, -0.64% to 0.98%), and 1.19 (95% CI, 0.84-1.70) for oral vs topical terbinafine-exposed (ARD, 1.13%; 95% CI, -2.23% to 4.50%) pregnancies. Conclusions and Relevance Among pregnancies exposed to oral or topical terbinafine, no increased risk of major malformations or spontaneous abortion was identified. Question Is terbinafine use in pregnancy associated with an increased risk of major malformations and spontaneous abortion? Findings This Danish nationwide cohort study included all pregnancies with use of oral and topical terbinafine in pregnancy during the study period 1997-2016 (n = 4065) as well as 40;650 unexposed pregnancies. In propensity score-matched comparisons, no significant differences in the risk of major malformations or spontaneous abortion between oral terbinafine-exposed, topical terbinafine-exposed, and unexposed pregnancies were identified. Meaning Oral or topical terbinafine use in pregnancy does not appear to be associated with an increased risk of major malformations or spontaneous abortion. This cohort study examines the association between use of oral or topical terbinafine and malformations and spontaneous abortions in women who receive terbinafine during pregnancy.