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CYP2C19 and 2C9 genotypes were not major determinants of voriconazole metabolism. No toxic serum level of voriconazole or its metabolites could be identified.

As part of a prospective natural history cohort study of voriconazole toxicity, we describe the characteristics of 12 of 72 voriconazole-treated patients who experienced hallucinations from March 2006 through November 2007. Hallucinations associated with voriconazole use are not uncommon. Doctors should be aware of this complication, and the recipients of the drug should be reassured that the hallucinations are an effect of the drug.

This is a comprehensive, clinically oriented review of the four commercially available triazoles: fluconazole, itraconazole, voriconazole, and posaconazole. Emphasis is placed in pharmacology, drug interactions, adverse events, antifungal activity, and the evolving perspective of their clinical use. Key clinical trials are briefly discussed, and specific drug indications summarized. Fluconazole remains a valuable low-cost choice for the treatment of various fungal infections, including candidiasis and cryptococcosis. It has relatively few drug interactions and is safe but lacks activity against filamentous fungi. The use of itraconazole is historically plagued by erratic bioavailability of the oral capsule, improved with the oral solution. Drug interactions are numerous. Itraconazole exhibits significant activity against Aspergillus and the endemic fungi. Voriconazole has revolutionized the treatment of aspergillosis in severely immunocompromised patients, but its use is compromised by complicated pharmacokinetics, notable drug interactions, and relatively significant adverse events. Finally, posaconazole is the last addition to the azole armamentarium with extended antifungal spectrum, significant activity against the zygomycetes, and, apparently, optimal safety profile. Posaconazole has a significant role for the prophylaxis of invasive fungal infections in severely immunocompromised patients. Multiple daily dosing, a need for fatty foods for absorption, and absence of an intravenous formulation restrict its use to selected populations.