Clinical Relevance of the Pharmacokinetic Interactions of Azole Antifungal Drugs with Other Coadministered Agents

Abstract

There are currently a number of licensed azole antifungal drugs; however; only 4 (namely, fluconazole, itraconazole, posaconazole, and voriconazole) are used frequently in a clinical setting for prophylaxis or treatment of systemic fungal infections. In this article, we review the pharmacokinetic interactions of these azole antifungal drugs with other coadministered agents. We describe these (2-way) interactions and the extent to which metabolic pathways and/or other supposed mechanisms are involved in these interactions. This article provides an overview of all published drug-drug interactions in humans (either healthy volunteers or patients), and on the basis of these findings, we have developed recommendations for managing the specific interactions.

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

“…12 Drugs metabolised by the same CYP enzymes often interact, 13,14 and several websites detail the role of CYP enzymes in drug interactions (for example, http:// bioinformatics.charite.de/supercyp/index.php?site ¼ home, http://medicine.iupui.edu/clinpharm/ddis/ and http://www. drugbank.ca/).…”

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT

“…8 Of the antimycotic drugs used for the treatment of invasive aspergillosis, voriconazole poses a high risk for pharmacokinetic DDIs, as it is a known substrate and inhibitor of several cytochrome P450 isozymes (CYP), for example, CYP 2C19, 2C9 and 3A4. [9][10][11] Nivoix et al 10 considered voriconazole as a moderately strong CYP inhibitor, showing a two to fivefold increase in area under the curve values of sensitive CYP 3A4 substrates. Immunosuppressants such as CYA, sirolimus and tacrolimus are commonly used in HSCT recipients and are known substrates of CYP 3A4.…”

Antifungal stewardship considerations for adults and pediatrics

“…Managing the DDI includes knowledge of the pharmacologic properties of azoles and immunosuppressive drugs in order to predict the potential clinical relevance of a potential DDI; appropriate monitoring of liver and/or renal tests; education to primary providers and patients; and TDM. 87,88 Various tools to assist ASPs in managing these DDIs are also available. 89 …”