Triazole antifungals

Fluconazole

Azoles

• Imidazoles: topical, oral

• Triazoles: oral, IV

• Inhibition of 14-alpha demethylase, a fungal cytochrome P450 → ↓ fungal synthesis of ergosterol from lanosterol → ↓ levels of ergosterol → membrane instability → cellular death. [10]

• Ketoconazole: inhibition of 17α-hydroxylase/17,20-lyase

Triazole derivatives

• Drug of choice maintenance therapy of cryptococcal meningitis in patients with AIDS [11]

• Candidiasis (all forms)

• Coccidioidomycosis

• Histoplasmosis

• Blastomycosis

• Local burning sensation

• Pruritus

• Hepatotoxicity: inhibits cytochrome P450 → ↑ concentration of many drugs metabolized by CYP450 (e.g., warfarin, simvastatin, cyclosporine, theophylline)

• Gynecomastia due to inhibition of testosterone synthesis (especially seen with ketoconazole)

• Gastrointestinal upset

• QT prolongation → torsade de pointes

• Hypokalemia

• Ketoconazole: adrenal cortex insufficiency

• Voriconazole: dose-dependent, reversible visual disorders (e.g., photosensitivity)

• Cardiac arrhythmias

• Severe cardiac insufficiency

• Inhibition of cytochrome P450 can influence serum concentrations of other medications

• Cautious use in patients with renal and/or hepatic dysfunction

• PPIs must be discontinued (azoles require a low pH to be absorbed)