ravuconazole and Foot-Dermatoses

Onychomycosis is a frequent nail disease caused by dermatophytes, yeasts, and nondermatophyte molds. Trichophyton rubrum, T mentagrophytes, and Epidermophyton floccosum are the most common etiologic agents worldwide. Candida spp are the most frequent among the yeasts. Diagnosis is corroborated by direct microscopic examination, culture, and histomycology with periodic acid-Schiff stain. Other new methods of diagnosis are discussed. Treatment is based on oral antifungals: terbinafine, itraconazole, and fluconazole, including other emerging triazole drugs. Therapeutic outcome with ciclopirox and amorolfine lacquers alone and combined with systemic therapy are also reviewed, as well as the new nail enhancers and physical and chemical removal of the diseased nails.

Topics: Administration, Cutaneous; Administration, Oral; Antifungal Agents; Ciclopirox; Drug Administration Schedule; Drug Therapy, Combination; Fluconazole; Foot Dermatoses; Humans; Itraconazole; Mitosporic Fungi; Morpholines; Naphthalenes; Onychomycosis; Pyridones; Pyrimidines; Terbinafine; Thiazoles; Triazoles; Voriconazole

Fosravuconazole L-lysine ethanolate (F-RVCZ) is a prodrug of ravuconazole, a novel triazole antifungal agent, exerting broad and potent antifungal activity. The efficacy and safety of F-RVCZ, compared with a placebo, were investigated in a multicenter, double-blind, randomized study of Japanese onychomycosis patients with 25% or more clinical involvement of the target toenail. Subjects (n = 153) were randomly assigned to receive F-RVCZ (100 mg RVCZ, n = 101) or placebo (n = 52) p.o. once daily for 12 weeks. The primary end-point was the rate of complete cure (clinical cure [0% clinical involvement of the target toenail] plus mycological cure [negative potassium hydroxide examination]) at week 48 (36-week post-treatment visit). Secondary end-points were changes over time in the efficacy and mycological effect of F-RVCZ. Safety was also evaluated. The complete cure rate at week 48 was significantly higher with F-RVCZ (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (P < 0.001). The mycological cure rate at week 48 was also significantly higher with F-RVCZ (82.0%, 73/89) than the placebo (20.0%, 10/50, P < 0.001). Regarding safety, adverse events were observed in 83.2% (84/101) and 80.8% (42/52), and adverse drug reactions (ADR) in 23.8% (24/101) and 3.8% (2/52) of F-RVCZ and placebo subjects, respectively. ADR were mild to moderate in severity, with none being serious. F-RVCZ (equivalent to 100 mg ravuconazole) administrated once daily for 12 weeks was more effective than placebo and tolerable in patients with onychomycosis, suggesting it to be a promising drug for onychomycosis treatment.

Topics: Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Prodrugs; Thiazoles; Treatment Outcome; Triazoles; Young Adult

To determine the effectiveness and safety of ravuconazole in the treatment of toenail onychomycosis.. A phase I/II randomized, double-blind, double-dummy, placebo-controlled, dose-ranging study. Four 12-week dosing regimens were used: 200 mg/day; 100 mg/week; 400 mg/week and placebo. Subjects returned at weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 36 and 48 for assessment. Subjects were enrolled at 10 dermatology practices (seven in the United States, one in Canada, two in France).. Adults with distal subungual onychomycosis of one great (hallux) toenail (minimum area of 25%), and at least 2 mm of proximal nail clear of disease were selected. Onychomycosis was confirmed by direct microscopy and/or fungal culture. Subjects with conditions known to produce abnormal-appearing nails were excluded. One hundred and fifty-one subjects were randomized in a 2:2:2:1 ratio to the treatments above.. Primary efficacy was the effective cure rate at week 48 (mycological cure, and clinical cure or > 30% improvement).. Effective cure was found in 56% of subjects using 200 mg/day. Effective cure was 10% in subjects receiving 100 mg/week, 8% of subjects using 400 mg/week, and 15% of subjects using placebo. Mycological cure was seen in 59% of subjects in the 200-mg/day group, which was significantly higher than the rates found in the other groups. Drug-related adverse events were infrequent in all treatment arms. Headache was the most frequently reported event. Abnormal laboratory tests were infrequent over the 12 weeks of dosing. Abnormal laboratory findings with increases beyond normal of Grade 2, 3 or 4 were found in 8/148 subjects (5.4%). Only the 200 mg daily regimen had a mean plasma steady state concentration of ravuconazole exceeding the MIC(90) adjusted for 98% protein binding (3000 ng/mL).. For the treatment of onychomycosis, ravuconazole 200 mg/day for 12 weeks is the most effective of the regimens investigated. The safety of all regimens was acceptable. The concentrations of ravuconazole in the plasma compared to the adjusted MIC(90) may be useful in predicting the clinical and mycologic response of therapy.

Topics: Administration, Oral; Antifungal Agents; Double-Blind Method; Drug Administration Schedule; Foot Dermatoses; France; Humans; Nails; Ontario; Onychomycosis; Severity of Illness Index; Thiazoles; Treatment Outcome; Triazoles; United States