Background: Fluconazole is used to manage invasive fungal infections; but, resistance has been increasing due to the
rising prevalence of non-Candida species and lack of activity against opportunistic mold infections. Newer drugs including
itraconazole, voriconazole, and posaconazole are mold-active triazoles (MAT) with broader activity; but, complex
pharmacokinetics and interactions with concomitant drugs via various pathways can lead to adverse events. This study
evaluated the prevalence of potential drug-drug interactions (PDDI) where 2 or more interacting drugs were used
Methods: Cerner HealthFacts, an electronic medical record with over 110 million hospitalizations, was used for this
analysis (2005-2013). The study population was hospitalized US adults with MAT use. The first MAT used during any
hospitalization was defined as the index triazole and index hospitalization. PDDIs were categorized using drug labels and
DRUGDEX, an evidence-based system that classified interactions into 4 groups (contraindicated; major; moderate; minor).
Minor PDDIs were not counted. A random hospitalization was chosen if a patient had multiple eligible hospitalizations. A
PDDI event was considered to have occurred if both conditions were met: 1) used at least one drug with at least a
moderate interaction classification with the index triazole during the index hospitalization and 2) there was at least a 1-day
administration overlap between the index triazole and the given drug.
Results: 6962 hospitalizations were identified with MAT use, of which 6101 (87.6%) had evidence of a PDDI. 88% of
voriconazole (n=4751), 86% of itraconazole (n=1784), and 93% of posaconazole (n=417) users had a PDDI. 26% of all
hospitalizations with MAT use had at least 1 contraindicated PDDI, the most severe PDDI classification. 68% of
hospitalizations with posaconazole, 34% of itraconazole, and 20% of voriconazole had at least 1 contraindicated PDDI. The
most common drug interaction among all 3 MATs was with ondansetron.
Conclusion: Although this study could not directly assess the proportion of PDDIs that actually led to clinical events, the
findings suggest that a majority of hospitalized patients receiving MATs were at risk for severe drug-drug interactions
based on the concomitant medications assessed.
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