Antifungal agents that include fluconazole and voriconazole are not more effective than amphotericin but have improved safety profile allowing empirical and prophylactic use.
Triazoles have numerous clinically significant drug interactions, most of these interactions arise from competitive inhibition of liver oxidative metabolism via rapid reversible binding to CYP450 system enzymes.
Triazoles interfere mainly with CYP3A4, CYP2C9, and CYP2C19.
Itraconazole and posaconazole, but not fluconazole and voriconazole, are inhibitors of gastric P-glycoprotein.
P-glycoprotein is a transmembrane efflux pump limiting systemic exposure to many drugs by inhibiting GI absorption.
Thus inhibition of P-glycoprotein by azoles may lead to increased systemic exposure of drugs affected by this transport system.