nnd-502 and Foot-Dermatoses

Luliconazole is a novel, broad-spectrum, imidazole antifungal under development in the USA as a treatment for dermatophytic skin and nail infections. In vitro, luliconazole is one of the most potent antifungal agents against filamentous fungi including dermatophytes. Luliconazole has been formulated in a 10% solution with unique molecular properties, which allow it to penetrate the nail plate and rapidly achieve fungicidal levels in the nail unit. These properties make luliconazole a potent compound in the treatment of onychomycosis. This article reviews the development of luliconazole solution, 10% its molecular properties, preclinical and clinical data and its future perspectives for the treatment of fungal infections.

Topics: Administration, Topical; Antifungal Agents; Foot Dermatoses; Humans; Imidazoles; Onychomycosis; Pharmaceutical Solutions

Onychomycosis is a highly prevalent and intractable disease. The first-line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double-blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20-50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end-point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.

Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Foot Dermatoses; Humans; Imidazoles; Japan; Male; Microscopy; Middle Aged; Onychomycosis; Pharmaceutical Solutions; Tinea; Treatment Outcome; Trichophyton; Young Adult

We report a case of contact dermatitis caused by both efinaconazole, a topical triazole antifungal drug, and luliconazole, a topical imidazole antifungal drug. Positive patch test reactions were observed with efinaconazole and luliconazole. A patch test with lanoconazole also elicited a positive reaction. We hypothesized that structural similarity between luliconazole and lanoconazole led to cross-reaction, and that the dithiolane ring common to both drugs or the structure of the vinyl imidazole with a dithiolane ring could be the antigenic determinant. Since efinaconazole and luliconazole have no common structures, patients could be sensitized to both drugs separately. The antigenic determinant of efinaconazole is unknown. However, the chemical formula of ravuconazole, an oral triazole antifungal drug, is similar to that of efinaconazole. Clinicians should carefully consider potential cross-reactivity between these drugs.

Topics: Administration, Topical; Aged; Antifungal Agents; Dermatitis, Contact; Epitopes; Foot Dermatoses; Humans; Imidazoles; Male; Patch Tests; Triazoles

Topics: Allergens; Antifungal Agents; Dermatitis, Allergic Contact; Diagnosis, Differential; Female; Foot Dermatoses; Humans; Imidazoles; Middle Aged; Patch Tests; Tinea Pedis