properly. Photodynamic therapy, plasma, and over-the-counter treatments (eg, tea tree oil, mentholated vapor rub) are not FDA approved and while some have reported good efficacy, results would have to be corroborated in larger clinical trials before they can be broadly recommended.14,26,27 Lasers are US FDA approved for temporary increase in clear nail; however, the FDA requires less stringent endpoints for device approvals and cure rates are typically lower than those of orals and topicals, and as such, they cannot be directly compared.26
Oral medications
In the US, there are three oral medications approved for adults for onychomycosis treatment: terbinafine (250 mg QD for 12 weeks)7; itraconazole (200 mg QD for 12 weeks)8; and griseofulvin (375 mg QD for at least 6 months).28 These medications have also been used off label for children and dosed according to weight.26 Fluconazole (eg, 150, 300, or 450 mg once-weekly for 6–12 months [adults]29) is used off label in adults and children either when traditional medications fail or prior to using itraconazole.
Terbinafine has shown higher complete and mycologic cure rates than itraconazole in adults (Table 1); the greater efficacy of terbinafine versus oral azoles (including itraconazole) was confirmed with moderate quality evidence in a 2017 Cochrane review.30 Griseofulvin requires a longer treatment time, has lower efficacy, and has higher relapse rates versus itraconazole and terbinafine.12 Finally, while fluconazole may not be as effective as other orals,31 once-weekly dosing may be more convenient for some patients.12 In terms of safety, itraconazole has black box warnings in patients with cardiac dysfunction.8 Furthermore, all oral medications have known drug-drug interactions (some more extensive than others) and are contraindicated in certain populations, including those with liver disease; as such, a patient’s concomitant medications and comorbidities must be assessed prior to determining treatment (see Recommended Medications section). The same Cochrane review above determined that the adverse event risk was similar between terbinafine and azoles (moderate quality evidence) and higher in griseofulvin than azoles or terbinafine (low to moderate quality).30
Topical medications
There are three topical medications approved in the US for both adults and children: ciclopirox 8% nail lacquer (patients aged ≥12 years)32; tavaborole 5% solution (≥6 years)18; and efinaconazole 10% solution (≥6 years).17 All three require once-daily application for 48 weeks; ciclopirox also requires regular nail filing and debridement. While head-to-head comparisons are difficult to make across studies, efinaconazole has demonstrated the highest complete and mycological cure rates for topicals (Table 1). Furthermore, these efficacy findings were confirmed with moderate to high quality evidence in a 2020 Cochrane review of clinical studies in adults.33 This review also determined that efinaconazole had a lower risk of adverse events (high quality evidence) than ciclopirox (low quality) or tavaborole (moderate quality).
A meta-analysis examining efficacy of topical and oral medications in adult onychomycosis showed that mycologic cure rate with terbinafine was superior to topicals.31 When comparing data from phase 3 adult clinical trials, complete cure rates with topicals were numerically lower than oral treatments, through efinaconazole had higher mycologic cure rates versus itraconazole (Table 1). It is important to note, however, that comparisons are challenging for drugs approved nearly two decades apart, particularly since the onychomycosis being treated today may be different from when oral treatments were first approved in the US in the 1990s. In addition, there are differences in clinical trial design and patient demographics and characteristics.
Oral medications
In the US, there are three oral medications approved for adults for onychomycosis treatment: terbinafine (250 mg QD for 12 weeks)7; itraconazole (200 mg QD for 12 weeks)8; and griseofulvin (375 mg QD for at least 6 months).28 These medications have also been used off label for children and dosed according to weight.26 Fluconazole (eg, 150, 300, or 450 mg once-weekly for 6–12 months [adults]29) is used off label in adults and children either when traditional medications fail or prior to using itraconazole.
Terbinafine has shown higher complete and mycologic cure rates than itraconazole in adults (Table 1); the greater efficacy of terbinafine versus oral azoles (including itraconazole) was confirmed with moderate quality evidence in a 2017 Cochrane review.30 Griseofulvin requires a longer treatment time, has lower efficacy, and has higher relapse rates versus itraconazole and terbinafine.12 Finally, while fluconazole may not be as effective as other orals,31 once-weekly dosing may be more convenient for some patients.12 In terms of safety, itraconazole has black box warnings in patients with cardiac dysfunction.8 Furthermore, all oral medications have known drug-drug interactions (some more extensive than others) and are contraindicated in certain populations, including those with liver disease; as such, a patient’s concomitant medications and comorbidities must be assessed prior to determining treatment (see Recommended Medications section). The same Cochrane review above determined that the adverse event risk was similar between terbinafine and azoles (moderate quality evidence) and higher in griseofulvin than azoles or terbinafine (low to moderate quality).30
Topical medications
There are three topical medications approved in the US for both adults and children: ciclopirox 8% nail lacquer (patients aged ≥12 years)32; tavaborole 5% solution (≥6 years)18; and efinaconazole 10% solution (≥6 years).17 All three require once-daily application for 48 weeks; ciclopirox also requires regular nail filing and debridement. While head-to-head comparisons are difficult to make across studies, efinaconazole has demonstrated the highest complete and mycological cure rates for topicals (Table 1). Furthermore, these efficacy findings were confirmed with moderate to high quality evidence in a 2020 Cochrane review of clinical studies in adults.33 This review also determined that efinaconazole had a lower risk of adverse events (high quality evidence) than ciclopirox (low quality) or tavaborole (moderate quality).
A meta-analysis examining efficacy of topical and oral medications in adult onychomycosis showed that mycologic cure rate with terbinafine was superior to topicals.31 When comparing data from phase 3 adult clinical trials, complete cure rates with topicals were numerically lower than oral treatments, through efinaconazole had higher mycologic cure rates versus itraconazole (Table 1). It is important to note, however, that comparisons are challenging for drugs approved nearly two decades apart, particularly since the onychomycosis being treated today may be different from when oral treatments were first approved in the US in the 1990s. In addition, there are differences in clinical trial design and patient demographics and characteristics.
