Voriconazole (Vfend), a derivative of fluconazole, is a second-generation triazole that has improved antifun-gal activity against Aspergillus and Fusarium spp., P. boydii, Penicillium marneffei, and fluconazole-resistant Candida spp. Like fluconazole, voriconazole has high oral bioavailability and good cerebrospinal fluid pene-tration, but unlike fluconazole, it undergoes extensive hepatic metabolism and is highly protein bound. No sig-nificant amount of bioactive drug is excreted into the urine. Dosage reduction is necessary with severe he-patic insufficiency but not with renal insufficiency.
Significant drug interactions include cyclosporins (increased cyclosporine levels), phenytoin, rifampin, and rifabutin (decreased voriconazole levels). Because of its low toxicity profile, this drug may gain importance in the chronic treatment of infections with invasive di-morphic fungi and resistant Candida spp.