Fluconazole: Effects, Uses & Risks

Fluconazole is used as an antifungal agent in the therapy of fungal infections due to its fungistatic effect. The active ingredient is used in particular when local or topical (external) therapy of fungal infections remains ineffective.

What is fluconazole?

Fungal infections of the skin and nails as well as mucous membranes (including vaginal fungus, oral thrush) can be effectively treated with the drug. For this purpose, fluconazole can be applied, for example, in capsules or as an injection preparation. Fluconazole is an azole antifungal agent which, as a triazole derivative, belongs to the group of imidazoles and triazoles. The active ingredient is used in the treatment of infections with human pathogenic fungi. Fluconazole itself is a whitish, crystalline powder that is difficult to dissolve in water. The triazole derivative inhibits the growth and multiplication of pathogens, especially yeasts of the Candida genus, through its cytostatic or fungistatic action. Fungal infections of the skin and nails as well as mucous membranes (including vaginal fungus, oral thrush) can be effectively treated with the drug. For this purpose, fluconazole can be applied in capsules, as an injection preparation or suspension.

Pharmacological action

Fluconazole, like all representatives of the imidazoles and triazoles, acts fungistatically by inhibiting (inhibiting) the construction of the cell walls of yeast fungi and thus their growth or multiplication. Depending on the dosage, the active ingredient can also have a fungicidal (fungicidal) effect. After application, the active ingredient enters the bloodstream either via the gastrointestinal tract (e.g. oral hard capsules) or directly (intravenous injections) and is distributed throughout the organism. In contrast to the human cell membrane, which consists of cholesterol, among other things, ergosterol is the most important building block of the cell membrane of yeast fungi. Fluconazole inhibits an enzyme in the cytochrome P450 system that is important for the synthesis of ergosterol, known as 14-alpha-demethylase, thereby blocking the conversion of lanosterol to ergosterol. The building materials modified by the blockade lead to defects in the cell membrane of the yeast fungi and impair certain metabolic processes that control the division of the fungal cells. The pathogens can no longer multiply (fungistatic effect). On the demethylase of the human organism, however, fluconazole has a significantly weaker inhibitory effect.

Medical use and application

Fluconazole is used particularly in the context of systemic (internal) therapy of infections with yeasts of the Candida genus (so-called cadidoses), among which Candida albicans is the most important representative. As a rule, only the skin and/or nails (nail and athlete’s foot infections) or the mucous membranes (oral thrush, vaginal thrush) are affected by candidiasis. In immunocompromised people, a fungal infection can also affect the internal organs in rare cases. Accordingly, fluconazole can also be used prophylactically to prevent fungal infection in people who have a weakened immune system as a result of chemotherapy and/or radiotherapy measures. In addition, fluconazole has been shown to be effective in the treatment of meningitis (inflammation of the meninges) caused by infections with the yeast Cryptococcus neoformans. Fluconazole can also be used prophylactically in HIV-affected individuals who have an increased prevalence for this specific fungal infection (opportunistic infection). If local or topical application of other antifungal agents is unsuccessful for vaginal candidiasis, fluconazole may be used alternatively as part of systemic treatment. In some cases (approximately 10 percent), the pathogens develop resistance to fluconazole, so the agent must be substituted with other antifungal drugs such as flucytosine or amphotericin B.

Risks and side effects

Fluconazole, as a comparatively newer member of the triazoles, is characterized by significantly fewer side effects and drug interactions compared with older agents in this group. Nevertheless, therapy with fluconazole is not completely risk-free and may correlate with various side effects. For example, therapy with fluconazole is often associated with nausea, vomiting, and gastrointestinal symptoms such as abdominal pain and diarrhea. Increased enzyme levels for alkaline phosphatase and aminotransferases are also frequently observed.In some cases, loss of appetite, digestive disturbances such as constipation or flatulence, dizziness, headache, cramps, increased sweat production, sensory disturbances such as tingling, liver impairment, jaundice, anemia, and weakness and fever may also be noted. Very rarely, angioedema, liver cirrhosis, tissue necrosis, and Stevens-Johnson syndrome, among others, may be associated with fluconazole therapy. Fluconazole is contraindicated in the presence of hypersensitivity to the active substance or other antifungal agents, in the presence of pronounced liver dysfunction, cardiac arrhythmias, and impaired cardiac function. In addition, the drug must not be applied during pregnancy, as an association with fetal malformations has been demonstrated in animal studies. Parallel therapy of fluconazole with terfenadine (antihistamine) or cisapride (prokinetic) should also be excluded.