Dimitrios I. Zonios; John E. Bennett

Disclosures

Semin Respir Crit Care Med. 2008;29(2):198-210. 

In This Article

Abstract and Introduction

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.

The azole antifungals include two classes, imidazoles and triazoles, which share the same mechanism of action. Imidazoles have a two-nitrogen azole ring; they are predominantly used topically and have been replaced for systemic administration by triazoles, which have three nitrogens in the azole ring. Triazoles have a more favorable pharmacokinetic profile than imidazoles and do not significantly inhibit human sterol synthesis. They were introduced almost 30 years ago. Triazoles include fluconazole, itraconazole, voriconazole, and posaconazole (Figure 1), each of which will be discussed in detail. Fluconazole and itraconazole were the first azoles in clinical practice. Newer azoles such as voriconazole and posaconazole have been developed to overcome the limited efficacy of fluconazole against Aspergillus and other molds and to improve absorption, tolerability, and drug interaction profile of itraconazole. Voriconazole is structurally similar to fluconazole and posaconazole to itraconazole.

Commercially available triazoles.

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