Voriconazole

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

Voriconazole is an antifungal used to treat serious infections of Aspergillus fumigatu, Candida, Scedosporium, Fusarium and other species. Voriconazole is metabolized in the liver by CYP2C19, CYP2C9 and CYP3A4. It also influences expression of metabolizing enzymes and interacts with several other drugs.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Voriconazole.

Excerpt from the Voriconazole (VFEND) drug label:
"Inhibitors and inducers of CYP3A4, CYP2C9, and CYP2C19 may alter VFEND concentrations. Adjust the VFEND dose and monitor for adverse events or lack of efficacy."

"VFEND may increase the concentrations and activity of drugs that are CYP3A4, CYP2C9 and CYP2C19 substrates. Reduce doses of and monitor for lack of efficacy or adverse events associated with drugs that are substrates of these enzymes."

"In vivo studies indicated that CYP2C19 is significantly involved in the metabolism of voriconazole. This enzyme exhibits genetic polymorphism. For example, 15¿20% of Asian populations may be expected to be poor metabolizers. For Caucasians and Blacks, the prevalence of poor metabolizers is 3¿5%. Studies conducted in Caucasian and Japanese healthy subjects have shown that poor metabolizers have, on average, 4-fold higher voriconazole exposure (AUCt) than their homozygous extensive metabolizer counterparts. Subjects who are heterozygous extensive metabolizers have, on average, 2-fold higher voriconazole exposure than their homozygous extensive metabolizer counterparts."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Voriconazole drug label PDF.