Voriconazole: A Novel Antifungal

Abstract

Objective: To review the published in vitro, in vivo, and clinical data and FDA background documents that led to the approval of voriconazole. Data Sources: Articles were identified by the referenced package insert and by a MEDLINE search (1966–October 2002) using the terms voriconazole, azole antifungal, aspergillosis, and UK-109, 496. Additionally, journal Web sites and abstracts from major infectious disease meetings were researched to obtain newly published data. Study Selection: All animal and human data published in journals, abstracts, and FDA background documentation were used. The only in vitro susceptibility testing studies used were those that incorporated a large number of fungal isolates. Data Synthesis: Voriconazole is a novel monotriazole antifungal agent that inhibits the fungal cytochrome P450–mediated 14 α-lanosterol demethylation. In vitro susceptibility studies, in vivo clinical trials, and case reports have shown potent activity against various Aspergillus spp., Scedosporium, and Fusarium. Additionally, voriconazole has shown in vitro activity against dimorphic fungi and yeast, including Candida spp. and Cryptococcus neoformans. The efficacy of voriconazole has been evaluated in 4 clinical trials. The clinical studies indicate that it is at least as effective as amphotericin B for the treatment of acute invasive aspergillus infection. The most common adverse effects in clinical trials included visual disturbances, rash, and elevated liver function tests. Voriconazole is metabolized by CYP2C19, CYP2C9, and CYP3A4 and thus causes multiple serious drug–drug interactions. Conclusions: Voriconazole provides an advance in therapy for the treatment of acute invasive aspergillus infection.