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Original Investigation
March 4, 2020

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

Author Affiliations
  • 1Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen NV, Denmark
  • 2Department of Epidemiology Research, Statens Serum Institut, Copenhagen S, Denmark
  • 3Department of Dermatology, Bispebjerg Hospital, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 4Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
JAMA Dermatol. 2020;156(4):375-383. doi:10.1001/jamadermatol.2020.0142
Key Points

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.

Abstract

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.

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