Fluconazole is a triazole antifungal drug which in sensitive fungi inhibits cytochrome P450-dependent enzymes, resulting in impairment of ergosterol synthesis in fungal cell membranes. It is active against Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Epidermophyton spp., Histoplasma capsulatum, Microsporum spp., and Trichophyton spp.
Fluconazole is a triazole antifungal used for superficial mucosal (oropharyngeal, esophageal, or vaginal) candidiasis and fungal skin infections. It is also employed for systemic infections, including systemic candidiasis, coccidioidomycosis, and cryptococcosis, and has been considered for blastomycosis, histoplasmosis, and sporotrichosis. The discussion on the role of fluconazole in the treatment of fungal infections can be found in various sections under the Choice of Antifungal.
The administration of fluconazole can be through oral or intravenous infusion, with similar doses. For intravenous infusion, a solution containing 2 mg/mL is given at a rate of 5 to 10 mL/minute (300 to 600 mL/hour). In the KENYA, a maximum infusion rate of 100 mL/hour is recommended. For superficial mucosal candidiasis (except genital candidiasis), the usual oral dose in the UK is 50 mg daily, although 100 mg daily may be given if necessary. Treatment duration varies, ranging from 7 to 14 days in oropharyngeal candidiasis, 14 days in atrophic oral candidiasis associated with dentures, and 14 to 30 days in other mucosal candidal infections, including esophagitis.
Higher doses are recommended in the KENYA, starting with an initial dose of 200 mg followed by 100 mg daily. The minimum treatment period is 14 days for oropharyngeal infection, or a minimum of 21 days and at least 14 days after resolution of symptoms for esophageal infections. Doses of up to 400 mg daily may be used for esophageal candidiasis if necessary.
For genital candidiasis, a single oral dose of fluconazole 150 mg may be used. Dermatophytosis, pityriasis versicolor, and Candida infections of the skin may be treated with fluconazole 50 mg daily orally for up to 6 weeks.
Systemic candidiasis, cryptococcal meningitis, and other cryptococcal infections can be treated with fluconazole orally or by intravenous infusion. The initial dose is 400 mg followed by 200 to 400 mg daily. Duration of therapy depends on clinical and mycological response but is usually at least 6 to 8 weeks in cryptococcal meningitis. In the KENYA, treatment for 10 to 12 weeks after cerebrospinal fluid cultures become negative is recommended. Fluconazole may also be used in daily doses of 100 to 200 mg orally or intravenously to prevent relapse after a primary course of antifungal treatment for acute cryptococcal meningitis in patients with AIDS.
In immunocompromised patients at risk of fungal infections, fluconazole may be given prophylactically in a dose of 50 to 400 mg daily orally or by intravenous infusion. However, long-term prophylaxis has been associated with the emergence of resistant organisms (see under Intermittent Doses, below).
Doses for children over 4 weeks of age are 3 mg/kg daily for superficial infections (a loading dose of 6 mg/kg may be used on the first day if necessary), and 6 to 12 mg/kg daily for systemic infections. For prophylaxis in immunocompromised children, a dose of 3 to 12 mg/kg daily may be given. For infants under 2 weeks of age, all these doses should be administered once every 72 hours; for those aged between 2 and 4 weeks, the doses should be given every 48 hours. A maximum dose of 400 mg daily should not be exceeded in children, or 12 mg/kg at appropriate intervals in infants.