Practical information on using azoles

The azoles are used systemically for fungal infections; their spectrums of activity vary:

• Fluconazole is active against yeasts, including Candida species¹ and Cryptococcus species.
• Itraconazole is active against yeasts, Sporothrix schenckii and some Aspergillus species.
• Isavuconazole is active against yeasts; Aspergillus species; some Scedosporium and Fusarium species; zygomycetes and phaeohyphomycetes.
• Voriconazole is active against yeasts, Aspergillus species, and some Scedosporium, Lomentospora and Fusarium species.
• Posaconazole is active against yeasts; Aspergillus species; some Scedosporium and Fusarium species; zygomycetes and phaeohyphomycetes.

Fluconazole has good tissue and central nervous system penetration.

Oral preparations of itraconazole are not bioequivalent; appropriate dosing and administration depends on the preparation. In these guidelines, the Lozanoc formulation of itraconazole capsules is recommended in preference to conventional itraconazole formulations because it has superior bioavailability and is not affected by pH.

The Itracap, Itranox or Sporanox (and bioequivalent brands of Sporanox) capsule formulation of itraconazole require an acidic environment for absorption, so absorption is reduced in patients taking proton pump inhibitors or histamine H₂-receptor antagonists. Absorption of itraconazole from the Sporanox oral liquid formulation is not affected by pH, but food impairs absorption.

Voriconazole plasma concentration should be monitored if prophylaxis or treatment is likely to be used for longer than a few days (see Monitoring voriconazole blood concentrations). Trough levels vary significantly between patients which is, in part, related to individual polymorphisms in the CYP2C19 gene. In patients who remain subtherapeutic after 2 appropriate dose adjustments, consider switching to an alternative antifungal and performing CYP2C19 genotype testing. See the Australian and New Zealand antifungal consensus guidelines for information about managing patients with a CYP2C19 genetic variant.

Absorption of posaconazole is more variable from the oral liquid formulation than the modified-release tablets. Absorption of posaconazole oral liquid requires an acidic environment, so absorption is reduced in patients taking proton pump inhibitors or histamine H₂-receptor antagonists. The oral liquid should be taken with a fatty meal for best absorption, or with an acidic beverage. Absorption of posaconazole modified-release tablets is not affected by the presence of food. Posaconazole can be given intravenously if oral therapy is not possible.

Azoles have many clinically significant drug interactions. Consult an appropriate resource on drug interactions if starting or stopping azoles in patients taking other drugs.

QT-interval prolongation has been reported with voriconazole; other azoles may also prolong the QT interval under certain conditions (eg when administered with other drugs that prolong the QT interval). For more information on drugs that prolong the QT interval, see the CredibleMeds website.

For information on monitoring azole plasma concentrations, see Monitoring antifungal blood concentrations.