Chapter 31 : Azoles

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This chapter focuses on itraconazole, voriconazole, posaconazole, ravuconazole, isavuconazole, albaconazole and their role in treating invasive aspergillosis. In a study it was found that patients receiving itraconazole more often had an increase in bilirubin, and this led to the approval of itraconazole for empiric therapy. Metabolism of voriconazole takes place in the liver via the hepatic CYP isoenzymes CYP3A4, CYP2C19, and CYP2C9. Three major and five minor metabolites have been identified which are eliminated within 48 h in the urine and feces. The major metabolite is voriconazole N-oxide, which represents approximately 72% of the metabolites in plasma. The major enzyme involved in the metabolism of voriconazole is CYP2C19, and this enzyme exhibits genetic polymorphism. Several case reports or short series have identified breakthrough fungal infections in patients receiving voriconazole. Posaconazole is an extended-spectrum triazole that is currently only available as an oral suspension. Importantly, the spectrum of activity is extended to Zygomycetes, and clinical trials have shown efficacy of posaconazole in invasive zygomycosis. The large variations in itraconazole, voriconazole, or posaconazole serum levels may be associated with decreased efficacy, increased toxicity, or occurrence of breakthrough infections. Itraconazole serum levels should be monitored in all patients treated with itraconazole capsules for a prolonged period for invasive fungal infections such as aspergillosis or histoplasmosis. Early identification of patients having very low serum drug levels and with low response rates, allows the switch to another therapy to increase the probability of efficacy of the antifungal treatment.

Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31
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Table 1.

Availability of anti- azoles and their approved indications

Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31
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Table 2.

In vitro activities of azoles and amphotericin B against spp. from clinical or environmental sources

Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31
Generic image for table
Table 3.

Main pharmacokinetics characteristics and recommended dosages for itraconazole, voriconazole, and posaconazole

Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31

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