High-dose therapy with fluconazole > or = 800 mg/day. Review

Abstract

The clinical use of fluconazole in dosages > or = 800 mg/day has been reported in about 900 patients against candidemia, oropharyngeal candidiasis and cryptococcal meningitis in HIV-infected patients as well as for initial therapy of endemic mycoses. Especially in patients with life-threatening infections caused by Candida spp., Cryptococcus neoformans and Coccidioides immitis, the results of a limited number of dose-finding trials with non-neutropenic and HIV-infected patients show dose-dependent response rates. These findings strongly advocate the application of high dose-fluconazole; their evaluation, however, still awaits final clarification. The good safety profile for dosages up to 2000 mg/day and the linear, predictable pharmacokinetics up to 1600 mg/day indicate the excellent tolerability of fluconazole in the clinical situation which justifies prospective, randomized clinical trials with treatment groups as homogeneous as possible for further evaluation of the optimum dosage and duration of treatment.