UPDATE ON DRUG-INTERACTIONS WITH AZOLE ANTIFUNGAL AGENTS

OBJECTIVE: To review and update the incidence, mechanism, and clinical relevance of drug interactions with itraconazole, ketoconazole, and f luconazole. DATA SOURCES: Literature was identified by MEDLINE search (from January 1990 to May 1997) using the name of each antifungal and the term ''interaction'' as MeSH headings. Abstracts were identified b y literature citation and by review of Interscience Conference on Anti microbial Agents and Chemotherapy from 1995 to 1996. STUDY SELECTION: Randomized, controlled, double-blind studies were emphasized; however, uncontrolled studies and case reports were also included. In vitro da ta were selected from literature review and citations. DATA EXTRACTION : Data were evaluated with respect to study design, clinical relevance , magnitude of interaction, and recommendations provided. DATA SYNTHES IS: The incidence of fungal infections and consequent azole antifungal usage continues to increase. By virtue of their antifungal mechanism (i.e., inhibition of cytochrome P450 fungal enzyme systems), azoles ha ve been investigated and implicated in several drug interactions. The magnitude of interactions can vary from trivial to potentially fatal, and also vary with specific azole and interactant. CONCLUSIONS: The az ole antifungal agents represent a commonly used class of agents with a broad range of potential interactions. Recent data have increased our understanding of drug-drug interactions with azoles. Pharmacists are in a unique position to identify these interactions and to intervene t o decrease their morbidity and improve patient care.