Clinical Information

Voriconazole (Vfend) is an antifungal agent approved for treatment of invasive aspergillosis and candidemia/candidiasis, as well as for salvage therapy for infections in patients refractory to, or intolerant of, other antifungal therapy. The drug inhibits the fungal enzyme 14a-sterol demethylase, a critical step in ergosterol biosynthesis.

Voriconazole is metabolized in the liver primarily by cytochrome P450 (CYP) 2C19 with CYP2C9 and CYP3A4 having limited roles. The primary metabolite is voriconazole N-oxide, which has no antifungal activity. Drug clearance is primarily dependent on hepatic metabolism. The pharmacokinetics of voriconazole is highly variable and nonlinear, which results in an increased dose leading to a greater than proportional increase in serum concentration.

The bioavailability of oral voriconazole is greater than 95%. Approximately 60% of the drug in serum is protein bound. Voriconazole has a volume of distribution of 4.6 L/kg. Most (80%) of the drug is excreted in the urine, exclusively as metabolites.

Adverse effects of voriconazole include visual disturbances, skin rashes, and elevated liver enzyme levels.