1. They interfere with ergosterol biosynthesis by inhibition of one or more fungal enzymes in the cytochrome P450 microsomal enzyme system.
2. Low concentrations are fungistatic, while higher concentrations are fungicidal.
3. They have a broad spectra of action against dermatophytes, Candida (most), Crypto- coccus, Coccidioides, Histoplasma, Blastomyces, & Paracoccidioides. Aspergillus & Fusarium are only moderately sensitive except to voriconazole. Zygomycetes such as Mucor are insensitive except to posaconazole.
4. *The systemic antifungal azoles cause very numerous drug interactions as a result of inhibition of specific human cytochrome P450 enzymes; ketoconazole and itraconazole are potent inhibitors of CYP3A4, fluconazole is a moderate blocker of CYP3A4 and a stronger blocker of CYP2C9, and voriconazole is a blocker of CYP2C19, CYP2C9, & CYP3A4. As a result, use of these agents with other drugs metabolized by any of these pathways can increase the concentration of other drugs, potentially to toxic levels. Conversely, use of certain drugs metabolized by specific pathways can either increase or decrease the concentration of the antifungal azole.
5. *All are teratogenic if administered to pregnant women. In infants exposed to fluconazole during gestation, a pattern of craniofacial & cardiac anomalies has been reported similar to those seen in animals. (Amphotericin B is preferred for systemic fungal infections in this situation.)
6. The major advantages of the newer azoles are that: a. They are better tolerated than amphoB or flucytosine. b. They can generally be given orally rather than IV even for serious infections. c. They do not require hospitalization.
ITRA-, FLU-, VORI-, POSA- & KETOCONAZOLE (systemic antifungal azoles)