New Topical Therapeutic Options in the Management of Superficial Fungal Infections

subjects in the luliconazole and vehicle groups, respectively (P<.001). 24.4% of patients using luliconazole achieved a clinical cure at day 28, compared with 6.6% using vehicle (P<.001). Finally, a statistically significant difference was observed in patients who experienced an effective treatment at the end of the study: 43% of the subjects in the luliconazole group compared with only 18.7% in the vehicle (P<.001).²⁰

Luliconazole was safe and well tolerated in the phase 3 studies. The most common treatment-related adverse events (AEs) were application site reactions, which occurred in less than 1% of patients who received both luliconazole and vehicle. Moreover, most were mild in severity.^20,21

Naftifine is a new topical allylamine class antifungal drug that exhibits broad-spectrum fungicidal activity. Naftifine hydrochloride cream is FDA-approved for the treatment of tinea pedis, tinea cruris, and tinea corporis. In 2014, a 2% gel and cream formulation was added to the previous line of 1% naftifine products. They are FDA-approved for the treatment of interdigital type tinea pedis in pediatric patients aged 12 to 17 years old.

The efficacy and safety of naftifine gel 2% in the treatment of interdigital and moccasin-type tinea pedis was evaluated in two 6-week, phase 3 double-blind, randomized, vehicle-controlled, multi-center, clinical trials. Subjects were recruited from 47 clinical sites within the US. The trials ultimately randomized a total of 1715 subjects: 1144 of the subjects received naftifine gel 2% and 571 received the vehicle.²²

Subjects in the study were randomized 2:1 to apply naftifine 2% gel or vehicle and followed for 6 weeks. The medication was applied once daily for 2 weeks followed by a 4 week post-treatment follow-up period. The primary efficacy variable was a complete cure at week 6, defined as both a mycological and clinical cure. Secondary efficacy variables included a mycological cure (negative KOH and culture) and effective treatment (mycological cure plus clinical signs no worse than mild).22 In the interdigital tinea pedis patients, naftifine showed a statistically significant (P=.001) complete cure rate compared with vehicle as early as week 2, and sustained until week 6. In addition, there were statistical differences between the active and vehicle arms with respect to mycological cure (P<.0001) and treatment effectiveness (P<.0001). In addition, statistical differences were observed at week 6 (P<.0001) for all endpoints in subjects with moccasin-type tinea pedis.²²

Naftifine gel was safe and well tolerated. Twenty-one subjects out of 1,143 using active drug experienced an AE, compared with 4 out of 571 on vehicle. Only 5 subjects from the naftifine group and 1 subject from the vehicle group discontinued from the study because of an AE. There were no serious AEs reported.²²

Efinaconazole is a new triazole antifungal indicated to treat onychomycosis caused by T. rubrum and T. mentagrophytes.²³ It received FDA approval in the U.S. in June 2014. The course of treatment for infected toenails is 48 consecutive weeks. Dispensed in an integrated flow-through brush applicator, the drug should be applied to cover completely the toenail, nail folds, and hyponychium, as well as beneath the nail plate. The drug is formulated as a non-lacquer solution. There is no buildup, nor periodic removal or debridement required.²³

Efinaconazole is an azole class antifungal. Similar to luliconazole, while the exact action is unknown, efinaconazole is thought to block the conversion of lanosterol to egosterol by inhibiting the fungal lanosterol 14α-demethylase enzyme. This decreases the amount of available ergosterol, disrupting production of the fungal cell membrane.²³ In vitro testing demonstrated efinaconazole to have excellent anti-fungal activity against T. rubrum and T. mentagrophytes. In addition, it was active against other trichophyton, microsporum, epidermophyton, and candida species.²⁴ At therapeutic concentrations, efinaconazole has not been shown to affect the cytochrome P450 (CYP450) enzyme system.²³

Several characteristics of efinaconazole 10% solution help explain its effectiveness in treating onychomycosis. First, it displays a low keratin binding affinity. Efinaconazole can bind to and be released from keratin, enhancing its antifungal activity.²⁵ Secondly, the solution has a low surface tension that enhances penetration and spreading or wicking of the drug around the