Clinical Question

What is the best oral monotherapy for toenail onychomycosis in adults?

Bottom Line

Based on effectiveness, safety, and cost, a regimen of terbinafine, 250 mg once daily for 12 weeks, followed by a 12-week period of no therapy and then a four-week booster, was preferred for onychomycosis in adults for the outcome of complete cure at one year. This POEM aligns with the Canadian Dermatology Association’s Choosing Wisely Canada recommendation: Do not prescribe systemic antifungals for suspected onychomycosis without mycologic confirmation of dermatophyte infection. (Level of Evidence = 1a−)

Synopsis

The goal of the network meta-analysis was to compare individual oral antifungal regimens directly and indirectly for onychomycosis in adults. The surface under the cumulative ranking curve (SUCRA), a measure of the likelihood that a regimen was more likely to be effective or to cause harms, was calculated for each study and outcome. The researchers identified a total of 21 studies. Study quality was mixed, with many studies failing to mask participants and/or physicians. An overall assessment of the quality of each study was not provided, although most were at moderate to high risk of bias. The highest complete cure rates at one year were found with terbinafine, 250 mg once daily for 12 weeks, followed by no treatment for 12 weeks and then terbinafine, 250 mg once daily for another four weeks (SUCRA = 82.7%); the same regimen, but with an initial treatment period of eight weeks (SUCRA = 80.4%); and albaconazole, 400 mg once weekly for 36 weeks (SUCRA = 80.4%). Terbinafine, 250 mg once daily for 24 weeks, had the highest likelihood of mycologic cure (SUCRA = 92.4%). Terbinafine, 250 mg daily for 12 weeks, was found to be significantly safer than albaconazole, 400 mg weekly for 36 weeks; oteseconazole (Vivjoa), 600 mg daily for two weeks, then 600 mg weekly for 10 weeks; fluconazole, 300 mg once weekly for 12 months; and posaconazole (Noxafil), 200 mg daily for 24 weeks. The price of terbinafine is low compared with that of newer agents such as albaconazole and posaconazole.