From the FDA Drug Label
For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used The recommended dosage of Fluconazole for Candida pneumonia is not established, but doses of up to 400 mg daily have been used in some studies 1.
From the Research
For candida pneumonia, the recommended fluconazole dosage is typically 400-800 mg (6-12 mg/kg) on the first day, followed by 200-400 mg (3-6 mg/kg) daily for at least 2 weeks after clinical improvement and resolution of symptoms. The most recent and highest quality study, 2, suggests that a fluconazole dose of >200 mg/day is associated with a higher 30-day survival rate and better microbiological response in patients with Candida albicans bloodstream infection. However, the study also notes that the role of fluconazole in the treatment of non-albicans Candida bloodstream infection is less clear.
Key Considerations
- Fluconazole is effective against most Candida species except C. krusei (intrinsically resistant) and some strains of C. glabrata (reduced susceptibility) 3, 4.
- Dosage adjustments are necessary for patients with renal impairment; reduce the dose by 50% if creatinine clearance is <50 mL/min.
- Fluconazole works by inhibiting fungal cytochrome P450 enzymes, preventing the synthesis of ergosterol, an essential component of the fungal cell membrane.
- Monitor liver function tests during treatment as hepatotoxicity can occur.
- For severe or refractory cases, alternative antifungals like echinocandins or amphotericin B may be necessary.
- Ensure adequate source control if there's a removable focus of infection.
Additional Guidance
- Treatment should continue until radiographic abnormalities resolve and cultures become negative.
- The study by 5 suggests that high-dose fluconazole may be an acceptable treatment strategy for patients with suspected invasive candidiasis, but this should be weighed against the potential for increased toxicity and cost.
- The study by 6 found that amphotericin B/5-flucytosine was more effective than fluconazole for the treatment of peritonitis, but fluconazole was associated with less toxicity.
- The study by 4 found that fluconazole was a viable therapy for C. glabrata fungemia, with bloodstream eradication in 65% of patients and mortality rates of 24% to 40%.