Background Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts and non-dermatophyte moulds that accounts for approximately 50% of all nail-related disease.
Objectives This study aims to assess the effectiveness and safety of monotherapy and combination treatments for toenail onychomycosis using a network meta-analysis (NMA).
Methods Quality of evidence was assessed using Cochrane-compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.
Results Of 77 randomized controlled trials, 26 were included in the ORs (8136 patients).

Relative effects show that the odds of mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg are significantly greater than topical treatments.

Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of mycological cure.

Conclusions Our review suggests that oral and topical treatments for toenail onychomycosis are safe and effective in producing mycological cure.



















Treatment (from UpToDate)

Continuous dosingOral: 250 mg once daily for 6 weeks (fingernail) or 12 weeks (toenail).

Pulsed dosing (alternative dosing method) (off-label): Oral: 250 mg once daily for 4 weeks, off for 4 weeks, then resume with 250 mg once daily for 4 weeks (Gupta 2013) or 250 mg twice daily for 1 week repeated every 4 weeks for 3 months (Takahata 2009; Yadav 2015). Note: Pulsed dosing is less effective but may reduce the risk of adverse effects, reduce cost, and improve patient compliance (Goldstein 2019).


Summary of Key findings This review set out to compare monotherapy (oral, topical and devices) and combination therapies for toenail onychomycosis. We were able to evaluate only oral and topical monotherapies for the outcomes mycological cure and adverse events. Oral and topical treatments demonstrated significantly greater ORs of achieving mycological cure compared with placebo. Continuous terbinafine 250 mg and continuous itraconazole 200 mg showed significantly greater ORs of attaining mycological cure compared with topical treatments. Pulse regimens of terbinafine and itraconazole, and fluconazole were not significantly different from topical treatments. Continuous terbinafine 250 mg was almost two times more likely to achieve mycological cure compared with pulse itra- conazole 400 mg (OR 195, 95% CI 104–365) and pulse terbinafine 500 mg (180, 95% CI 113–287; Lastly, there was no difference in the ORs of mycological cure among topical treatments. Quality of evidence was mostly moderate to high.