Azole Antifungal Drug Interactions

Mechanism of Interactions

Azoles function as potent inhibitors of multiple CYP450 isoenzymes, particularly CYP3A4, which metabolizes a vast array of medications 1, 2, 4
Azoles are inhibitors of P-glycoprotein, increasing systemic levels of drugs affected by this transport system 1, 4, 5
Azoles are substrates for CYP enzymes, making them vulnerable to interactions with enzyme inducers that can reduce azole levels 2, 3

Calcineurin inhibitors and mTOR inhibitors require 30-50% dose reduction when initiating azole therapy due to significant increases in CNI levels 2, 3
Combination of azoles with vinca alkaloids causes severe neurotoxicity, and alternative antifungal therapy should be used instead 2
Rifampin/rifabutin dramatically decreases azole levels and increases rifamycin levels, and combined use should generally be avoided 2, 3
Azoles cause QTc prolongation, creating additive risk when combined with QTc-prolonging medications 1, 4, 6
Corticosteroid levels are increased by azoles, potentially exacerbating immunosuppression 2, 3
Cyclophosphamide metabolite levels are increased with certain azoles, associated with hyperbilirubinemia and nephrotoxicity 1, 4
Tyrosine kinase inhibitors have significant interactions with azoles via CYP3A4, requiring therapeutic drug monitoring 2, 3, 7

Azoles should only be incorporated into treatment after consultation with an infectious disease expert due to the expansive list of drug-drug interactions 1, 5
Therapeutic drug monitoring is strongly recommended for itraconazole, voriconazole, and posaconazole suspension formulation 1, 2, 3, 5, 7
Monitor both azole levels and levels of interacting drugs, such as cyclosporine, tacrolimus, sirolimus, and tyrosine kinase inhibitors 2, 3, 7