Evaluation of Prevalence of Potential Drug-Drug Interaction among Patients with Invasive Fungal Infections Receiving Mold-Active Triazoles

DAVID ANDES, MD, FIDSA1, NKECHI AZ IE, MD2, HONGBO YANG, PHD3, CAROLINE KELLEY, BA3, RUO-DING TAN, PH.D.3, YICHEN Z HONG, MHS3, BILLY FRANKS, PHD4, RITA KRISTY, MS2, EDWARD LEE, PHARMD2, NIKHIL KHANDELWAL, PHD2 and JAMES SPALDING, PHARMD2;

Author address: 

1University of Wisconsin, Madison, WI, 2Astellas Pharma Global Development, Inc., Northbrook, IL, 3Analysis Group, Boston, MA, 4Astellas Pharma Europe B.V., Northbrook, IL

Abstract: 

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

concomitantly.

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.

2015

Full conference title: 

IDWeek 2015 San Diego, CA
    • IDWeek 2015