The continued search for new and less toxic antifungals led to the discovery of the azoles several decades later with the first release in the early 1980s. However, in the 1990s, new discoveries of both fluconazole and itraconazole displayed a broader spectrum of antifungal activity. Eventually, these agents became subject to a number of clinically important limitations related to their development of resistance, the induction of hazardous drug interactions and their performance as they moved throughout the body and their toxicity. ( 17 )
CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.
There are also many drug interactions . Patients must read in detail the enclosed data sheet(s) of the medicine. For example, the azole antifungals such as ketoconazole or itraconazole can be both substrates and inhibitors of the P-glycoprotein , which (among other functions) excretes toxins and drugs into the intestines.  Azole antifungals also are both substrates and inhibitors of the cytochrome P450 family CYP3A4 ,  causing increased concentration when administering, for example, calcium channel blockers , immunosuppressants , chemotherapeutic drugs , benzodiazepines , tricyclic antidepressants , macrolides and SSRIs .