Overview
Fluconazole is a triazole antifungal agent used to treat and prevent various fungal infections. It works by inhibiting fungal cytochrome P450 14α-demethylase, disrupting ergosterol synthesis in fungal cell membranes. It has excellent bioavailability, good tissue penetration, and is available in oral and intravenous formulations.
Mechanism of Action
Fluconazole inhibits fungal cytochrome P450-dependent enzyme lanosterol 14α-demethylase, which converts lanosterol to ergosterol. This disruption of ergosterol synthesis in fungal cell membranes increases membrane permeability and inhibits fungal growth.
Indications
- Vaginal candidiasis
- Oropharyngeal and esophageal candidiasis
- Cryptococcal meningitis
- Systemic candidiasis
- Candidal urinary tract infections
- Peritonitis
- Pneumonia
- Prophylaxis in immunocompromised patients
- Candidemia
Dosage
Dosage varies by indication: Vaginal candidiasis: 150 mg single dose; Oropharyngeal candidiasis: 200 mg first day, then 100 mg daily; Esophageal candidiasis: 200 mg first day, then 100 mg daily; Cryptococcal meningitis: 400 mg first day, then 200-400 mg daily; Prophylaxis: 50-400 mg daily. Adjust for renal impairment.
Contraindications
- Hypersensitivity to fluconazole or other azole antifungals
- Concomitant use with cisapride, terfenadine, astemizole, or erythromycin due to QT prolongation risk
- Concomitant use with pimozide or quinidine
Side Effects
- Headache
- Nausea
- Abdominal pain
- Diarrhea
- Rash
- Elevated liver enzymes
- QT prolongation
- Dizziness
- Taste disturbance
- Hepatotoxicity
- Stevens-Johnson syndrome
- Anaphylaxis
Interactions
- Warfarin: Increased anticoagulant effect
- Phenytoin: Altered levels of both drugs
- Cyclosporine: Increased cyclosporine levels
- Oral hypoglycemics: Enhanced hypoglycemic effect
- Rifampin: Decreased fluconazole levels
- Theophylline: Increased theophylline levels
- Zidovudine: Increased zidovudine levels
- Statins: Increased risk of myopathy