Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 CYP2C19; 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.
Monitoring trough levels of voriconazole is suggested in individuals with reduced liver function, individuals with CYP2C19 polymorphisms associated with poor metabolic function, patients taking other medications that affect CYP2C19 activity, and in patients experiencing potential toxicity
Monitoring trough levels may be reasonable in patients who are not responding optimally or have drug interactions that may decrease voriconazole levels, or to ensure adequate oral absorption
Trough levels above 6 mcg/mL (and especially >10 mcg/mL) have been associated with toxicity in several reports.
Trough levels below 1 mcg/mL have been associated with suboptimal response in several reports.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Voriconazole metabolism may be altered by coadministration of drugs that metabolically induce or inhibit CYP2C19 or by genetic polymorphisms that affect enzyme activity.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Trough level (ie, immediately before next dose) monitoring is recommended.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Andes D, Pascual A, Marchetti O: Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 2009;53(1):24-34
2. Hope WW, Billaud EM, Lestner J, Denning DW: Therapeutic drug monitoring for triazoles. Curr Opin Infect Dis 2008;21:580-586
3. Donnelly JP, De Pauw BE: Voriconazole-a new therapeutic agent with an extended spectrum of antifungal activity. Clin Microbiol Infect 2004;10:107-117
4. Physicians Desk Reference, (PDR) 60th edition. Medical Economics Company, Montvale, NJ, 2006 update to 2008
5. Goodman and Gilman's The Pharmacological Basis of Therapeutics. Edited by LL Brunton, 11th edition. New York, McGraw-Hill Book Company, 2006