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How well is long-term fluconazole tolerated?

March 04 2019

Fluconazole (Diflucan) has been taken by hundreds of millions of people since its launch in 1990 and remains an important drug for the management of many serious fungal infections. However, the original trials carried out to support approval did not address tolerability in the small number of patients need long-term fluconazole (>28 days), notably those with coccidioidal meningitis, recurrent vulvovaginal candidiasis, or chronic candida infections related to prosthetic devices or endocarditis.

Dr Matthew Davis and colleagues at UC Davis Health (Sacramento, California) retrospectively studied a group of 124 coccidioidomycosis patients and found that around half (52%) experienced significant side effects.

The commonest side effects were dry skin (xerosis), hair loss (alopecia) and fatigue. Other side effects included nausea and vomiting, loss of appetite, headache, joint discomfort, dry lips, dry mouth and loss of taste, dizziness or low blood pressure, neuropathy, impotence, anxiety, and brittle nails. Two thirds of those with adverse events needed some therapeutic intervention – additional medication, stopping fluconazole or lowering the dose.

As well as being of shorter duration, the original fluconazole studies were also based on a lower dosage than these patients — around 50–200 mg/day, with higher doses being introduced later for hospitalized patients such as those with candidaemia or cryptococcal meningitis. In this study a typical dose was 400 mg/day (range 100–1600 mg/day).

Fluconazole’s long-term profile is reminiscent of those of itraconazole or voriconazole (although not identical), highlighting the need for new antifungals to be developed that can be safely administered over longer time periods.