Search

Polypharmacy, defined as the concurrent use of five or more medications, is highly prevalent among older adults and patients with multiple chronic conditions and is associated with an increased risk of drug–drug interactions (DDIs), leading to adverse drug events, hospitalizations, and higher healthcare costs. Existing DDI databases are often incomplete and fail to capture higher-order interactions, while many machine learning approaches overlook temporal prescription patterns and molecular structure information, limiting their effectiveness in real-world clinical settings. To address these limitations, this study proposes a graph neural network (GNN)-based framework that integrates prescription sequence data with molecular representations to improve DDI prediction. The model constructs a unified graph where drug nodes encode both known interactions and learned similarities, while a prescription sequence encoder captures temporal co-prescribing patterns and a molecular encoder processes SMILES-based structures. These multimodal representations are fused within a patient–drug interaction graph and refined using GNN layers with attention mechanisms to enhance interpretability. By combining longitudinal clinical data with chemical structure information, the framework enables more accurate, context-aware, and patient-specific prediction of DDIs, supports the identification of novel interactions, and improves risk stratification in polypharmacy settings, offering a scalable and interpretable foundation for future clinical decision support systems.