Agents: fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, multiple topical formulations and minor variants
The azoles are the workhorse class of antifungal agents, used for fungal infections ranging from minor to life-threatening. They target the ergosterol component of the fungal cell membrane, but instead of binding to ergosterol like the polyenes, azoles inhibit ergosterol production. This is achieved through inhibition of cytochrome P450 enzymes-similar to the ones humans use in drug metabolism. Thus, the potential for drug-drug interactions with drugs metabolized by CYP enzymes is among the most significant concerns with systemically administered azole antifungals. Although many drug interactions can be successfully dealt with by dosage adjustment and/or monitoring, this is not universally true and serious outcomes can arise. Also, remember that any dose adjustments made while a patient is receiving an interacting drug need to be readjusted when the therapy with the interactor is finished.
In recent years, azoles of variable antifungal spectrums and toxicity profiles have been introduced. Thus, while they share mechanisms and propensities for drug interactions, it is important to know the individual characteristics of each drug. In particular, there are a variety of formulations of each agent that can have important differences with regards to administration with food and antacids (Table 31-1). This chapter discusses the commonly used systemic agents individually.