Fluconazole is an antifungal medication that is administered orally or intravenously. It is used to treat a variety of fungal infections, especially Candida infections of the vagina (“yeast infections’), mouth, throat, and bloodstream. It is also used to prevent infections in people with weak immune systems, including those with neutropenia due to cancer chemotherapy, transplant patients, and premature babies. Its mechanism of action involves interfering with synthesis of the fungal cell membrane.
Mechanism of action:
Like other imidazole and triazole-class antifungals, fluconazole inhibits the fungal cytochrome P450 enzyme 14alpha-demethylase. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase. This inhibition prevents the conversion of lanosterol to ergosterol,an essential component of the fungal cytoplasmic membrane and subsequent accumulation of 14α-methyl sterols. Fluconazole is primarily fungistatic; however, it may be fungicidal against certain organisms in a dose-dependent manner.
Following oral dosing, fluconazole is almost completely absorbed within two hours. Bioavailability is not significantly affected by the absence of stomach acid. Concentrations measured in the urine, tears, and skin are approximately 10 times the plasma concentration, whereas saliva, sputum, and vaginal fluid concentrations are approximately equal to the plasma concentration, following a standard dose range of between 100 mg and 400 mg per day. The elimination half-life of fluconazole follows zero order kinetics, and only 10% of elimination is due to metabolism, the remainder being excreted in urine and sweat. Patients with impaired renal function will be at risk of overdose.
Fluconazole is contraindicated in patients who:
• Have known hypersensitivity to other azole medicines such as ketoconazole
• Are taking terfenadine, if 400 mg per day multidose of fluconazole is administered
• Concomitant administration of fluconazole and quinidine, especially when fluconazole is administered in high dosages
• Take SSRIs such as fluoxetine or sertraline
Adverse drug reactions associated with fluconazole therapy include
Common: rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes
Infrequent: anorexia, fatigue, constipation
Rare: oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions.