Fluconazole - Uses (Indications), Mechanism Of Action, Pharmacokinetics, And Side Effects

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Fluconazole is a triazole antifungal agent.
It is effective against a wide range of fungal infections and is known for its relatively low toxicity and excellent oral bioavailability.
Fluconazole is indicated for the treatment and prophylaxis of various fungal infections, including the following.
Systemic fungal infections, such as cryptococcal meningitis.
Mucosal candidiasis, including oropharyngeal, esophageal, and vaginal candidiasis.
Dermatomycoses, including tinea infections.
Fungal infections in immunocompromised patients, such as those with HIV AIDS or undergoing chemotherapy.
And for prophylaxis of fungal infections in patients undergoing bone marrow transplantation.
Fluconazole works by inhibiting lanosterol 14α-demethylase, an enzyme required for the synthesis of ergosterol, an essential component of fungal cell membranes.
This disruption leads to increased membrane permeability and ultimately fungal cell death. Importantly, fluconazole selectively targets fungal enzymes with minimal effects on human cholesterol synthesis.
Fluconazole is available as oral tablets, capsules, and oral suspensions.
Intravenous route is reserves for severe or systemic infections.
Fluconazole is rapidly and almost completely absorbed from the gastrointestinal tract, with a bioavailability exceeding 90%.
It is widely distributed, including excellent penetration into the cerebrospinal fluid.
Fluconazole undergoes limited hepatic metabolism, up to 10-20% of the dose administered.
It is primarily excreted unchanged in the urine, and minor metabolites are also excreted renally.
Fluconazole has a long elimination half-life of about 20 to 50 hours, allowing once-daily dosing.
Major Adverse Effects of fluconazole include the following.
Gastrointestinal effects such as Nausea, vomiting, abdominal pain, and diarrhea.
Elevated liver enzymes and, rarely, hepatotoxicity or liver failure.
Rash, which can progress to Stevens-Johnson syndrome or toxic epidermal necrolysis in rare cases.
QT prolongation and torsade’s de pointes, especially in patients with other cardiac risk factors.
Rarely, leukopenia or thrombocytopenia.
Contraindications for the use of fluconazole include the following.

Known allergy to fluconazole or other azole antifungals.
Concurrent use of certain medications, especially with drugs that prolong the QT interval such as cisapride and astemizole, due to the risk of life-threatening arrhythmias.
Pregnancy, especially in high doses, because of the teratogenicity associated with fluconazole.
And severe renal or hepatic impairment.

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