Burden and Determinants of Drug–Drug Interactions at Hospital Discharge: Warfarin as a Model for High-Risk Medication Safety

<b>Background</b>: Potential drug-drug interactions (pDDIs) present substantial challenges to medication safety during care transitions. Warfarin, with its narrow therapeutic index and extensive interaction profile, provides a strategic model for examining pDDIs at discharge. This study aimed to characterize the burden and determinants of major warfarin pDDIs among patients discharged from a tertiary-care hospital. <b>Methods</b>: This retrospective cross-sectional study analyzed electronic health records of 1667 patients discharged home on warfarin. Major pDDIs were identified using the Micromedex^® Drug Interaction database. Log-binomial regression was used to assess predictors of ≥1 major pDDIs, and generalized Poisson regression was used to model the number of pDDIs per patient. <b>Results</b>: Major warfarin pDDIs were identified in 81.6% (95% CI: 79.6-83.4%) of patients at hospital discharge. The burden was considerable: 35.1% (95% CI: 32.8-37.4%) of patients had one major pDDI, while 46.5% (95% CI: 44.1-48.9%) had two or more. Polypharmacy (≥5 concurrent medications) was the strongest predictor, associated with a higher risk of any major pDDI (adjusted risk ratio 1.72, 95% CI: 1.46-2.02) and nearly three times the burden of interactions per patient (adjusted incidence rate ratio (IRR) 2.87, 95% CI: 2.36-3.49). When modeled as a continuous variable, each additional discharge medication was associated with a 9% increase in predicted pDDI burden (IRR 1.09, 95% CI: 1.08-1.10). <b>Conclusions</b>: Using warfarin as a model for high-risk medication safety, major pDDIs were highly prevalent at hospital discharge, with polypharmacy as a significant predictor of both the presence and burden of interactions. These findings emphasize the importance of identifying polypharmacy-related pDDIs to reduce potential drug interaction risk during care transitions.