fluconazole

Fluconazole is an antifungal medication in the triazole class, available in oral and intravenous formulations. It is used to treat a range of fungal infections and is often chosen for Candida species and Cryptococcus neoformans. Fluconazole works by inhibiting fungal 14-α-demethylase, an enzyme in the ergosterol synthesis pathway, which disrupts the integrity of the fungal cell membrane. It is generally fungistatic against most yeasts and has good central nervous system penetration.

Common indications include vulvovaginal candidiasis, oropharyngeal and esophageal candidiasis, cryptococcal meningitis, and systemic candidiasis in selected settings. It is also used for antifungal prophylaxis in some immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation. Its activity against molds is limited; most Aspergillus species are not reliably susceptible.

Pharmacokinetically, fluconazole is well absorbed orally with about 90% bioavailability and distributes widely, including into cerebrospinal fluid. It is primarily metabolized in the liver and excreted by the kidneys; the elimination half-life is longer in individuals with renal impairment, necessitating dose adjustments. The drug can be given once daily for many infections.

Adverse effects are generally mild but can include gastrointestinal symptoms, headache, rash, and elevated liver enzymes. Hepatotoxicity is rare but can occur, especially with long-term use. Fluconazole can interact with drugs metabolized by cytochrome P450 enzymes (for example warfarin, phenytoin, fentanyl, cyclosporine), so dose adjustments and monitoring may be required. Long-term therapy warrants liver function monitoring.

Resistance can arise, particularly in Candida species such as C. glabrata, through mutations in ERG11 or efflux mechanisms. In pregnancy, fluconazole is typically avoided in the first trimester unless clearly indicated.