Combination therapy of once-weekly fluconazole (100, 150, or 300 mg) with topical application of ketoconazole cream in the treatment of onychomycosis.

In order to assess the safety and efficacy of once-weekly fluconazole orally (100, 150, or 300 mg) with once-a-day topical application of 1% ketoconazole cream in the treatment of onychomycosis in Japan, 121 patients were assigned to one of three fluconazole dosages (100, 150, or 300 mg) and took fluconazole orally, once weekly, for 12 months or until a complete cure was achieved. In addition, once-a-day topical ketoconazole cream was applied. At each weekly visit, adverse events were investigated and the length of the diseased nails was measured. Treatment efficacy was assessed 12 months after discontinuation of fluconazole using the following scale: cured, markedly improved, improved, slightly improved, no change. Mycological cure was assessed using KOH wet mount and fungus culture. The results showed that the numbers of patients achieving marked improvement or better were 38/68 (55%), 13/22 (60%), and 21/31 (67%) for the 100 mg, 150 mg, and 300 mg groups, respectively. There was no significant difference between any two groups. The duration of fluconazole therapy was the longest for patients in the 100 mg group. None of the patients reported adverse effects. These findings led to the conclusion that once-weekly fluconazole with once-a-day application of topical ketoconazole cream appears safe and effective for treating onychomycosis. The dosage of 150 mg once weekly for 6 months was recommended, considering both effectiveness and economy.