ONCE-WEEKLY FLUCONAZOLE (150, 300, OR 450 MG) IN THE TREATMENT OF DISTAL SUBUNGUAL ONYCHOMYCOSIS OF THE TOENAIL

Background: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of sup erficial fungal infections. Objective: The purpose of this study was t o compare the efficacy and safety of three different doses of fluconaz ole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail cau sed by dermatophytes. Methods: In this multicenter, double-blind study , 362 patients with mycologically confirmed onychomycosis were randomi zed to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, p atients were required to have at least 25% involvement of the target n ail with at least 2 mm of healthy nail from the nail fold to the proxi mal onychomycotic border. Patients who were clinically cured or improv ed at the end of treatment were further evaluated over a 6 month follo w-up period. At both the end of therapy and the end of follow-up, clin ical success of the target nail was defined as reduction of the affect ed area to less than 25% or cure. Results: At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged cli nical successes as defined above-compared with 8% of placebo-treated p atients. Clinical cure (completely healthy nail) was achieved in 28% t o 36% of fluconazole-treated patients compared with 3% of placebo-trea ted patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The ra tes at the end of follow-up were very similar, indicating that eradica tion of the dermatophyte was maintained over the 6-month period. All e fficacy measures for the fluconazole groups were significantly superio r to placebo (p = 0.0001); there were no significant differences betwe en the fluconazole groups on these efficacy measures. The clinical rel apse rate among cured patients over 6 months of follow-up was low at 4 %. Fluconazole was well tolerated at all doses over the 12-month treat ment period, with the incidence and severity of adverse events being s imilar between the fluconazole and placebo treatment,groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 mo nths. This time frame may be used as a guideline for fluconazole treat ment duration. Conclusion: The results of this study support the use o f fluconazole in the treatment of distal subungual onychomycosis of th e toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as sa fe and well tolerated.