Fluconazole

Fluconazole is an antifungal medication used for a number of fungal infections. These include candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.

Common side effects include vomiting, diarrhea, rash, and increased liver enzymes. Serious side effects may include liver problems, QT prolongation, and seizures. Use during pregnancy may increase the risk of miscarriage or birth defects. Fluconazole is in the azole antifungal family of medication. It is believed to work by affecting the fungal cellular membrane.

Fluconazole was patented in 1981 and came into commercial use in 1988. It is on the World Health Organization's List of Essential Medicines. Fluconazole is available as a generic medication. In 2023, it was the 175th most commonly prescribed medication in the United States, with more than 2 million prescriptions.

Fluconazole is a first-generation triazole antifungal medication. It differs from earlier azole antifungals (such as ketoconazole) in that its structure contains a triazole ring instead of an imidazole ring. While the imidazole antifungals are mainly used topically, fluconazole and certain other triazole antifungals are preferred when systemic treatment is required because of their improved safety and predictable absorption when administered orally.

Fluconazole's spectrum of activity includes most species causing Candidiasis (but not Pichia kudriavzevii or Nakaseomyces glabratus, formerly known as Candida krusei and C. glabrata), Cryptococcus neoformans, some dimorphic fungi, and dermatophytes, among others.^{[medical citation needed]} Common uses include:

Antifungal resistance to drugs in the azole class tends to occur gradually over the course of prolonged drug therapy, resulting in clinical failure in immunocompromised patients (e.g., patients with advanced HIV receiving treatment for thrush or esophageal Candida infection).

In C. albicans, resistance occurs by way of mutations in the ERG11 gene, which codes for 14α-demethylase. These mutations prevent the azole drug from binding, while still allowing binding of the enzyme's natural substrate, lanosterol. Development of resistance to one azole in this way will confer resistance to all drugs in the class. Another resistance mechanism employed by both C. albicans and C. glabrata is increasing the rate of efflux of the azole drug from the cell, by both ATP-binding cassette and major facilitator superfamily transporters. Other gene mutations are also known to contribute to development of resistance. C. glabrata develops resistance by up regulating CDR genes, and resistance in C. krusei is mediated by reduced sensitivity of the target enzyme to inhibition by the agent.

The full spectrum of fungal susceptibility and resistance to fluconazole can be found in the product data sheet. According to the US Centers for Disease Control and Prevention, fluconazole resistance among Candida strains in the US is about 7%.