Abstract
Potential drug-drug interactions (DDIs) are a core concern across medical decision support systems. Among healthcare practitioners, the common practice for screening these interactions is via computer software. However, as real-world negative reporting is missing, counterexamples that serve as contradictory evidence may exist. In this study, we have developed an anti-DDI resource, a set of drug combinations having negative reported interactions. This resource was created from a set of the top 200 most-used drugs, resulting in 14365 prospective negative reported DDI pairs. During analysis and filtering, 2110 DDIs (14.69%) were found in publicly free DDI resources, another 11130 (77.48%) were filtered by a rule-based inference engine incorporating ten mechanisms of interaction, and 208 were identified through commercial resources. Additionally, 90 pairs were removed due to recent FDA approvals or being unapplicable in clinical use. The final set of 827 drug pairs represents combinations potentially having negative reported interactions. The anti-DDI resource is intended to provide a distinctly different direction from the state of the art and establish a ground focus more centered on the evaluation and utilization of existing knowledge for performing thorough assessments. Our negative reported DDIs resource shall provide healthcare practitioners with a level of certainty on DDIs that is worth investigating.