Voriconazole metabolism may be altered by coadministration of drugs that metabolically induce or inhibit cytochrome P450 2C19 or by genetic alterations that affect enzyme activity.
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; CYP2C9, and CYP3A4 play 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.
Trough level (ie, immediately before next dose) monitoring is recommended.
Voriconazole, S (88698)