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Treatment with the according to results from a large registry study in Denmark.
Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.
The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.
Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.
“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”
However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.
The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.
Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).
With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).
The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.
No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.
Treatment with the according to results from a large registry study in Denmark.
Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.
The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.
Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.
“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”
However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.
The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.
Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).
With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).
The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.
No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.
Treatment with the according to results from a large registry study in Denmark.
Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.
The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.
Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.
“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”
However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.
The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.
Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).
With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).
The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.
No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.
FROM JAMA DERMATOLOGY