Variability in Drug–Drug Interaction Identification Across Commonly Used Drug Information Resources: An Analysis of Real world Tertiary Care Prescriptions (Retrospective Cross sectional Study)

Objectives: This study aimed to evaluate and compare three popular drug interaction checkers – Lexidrug, Medscape, and Drugs.com – in detecting major drug–drug interactions (DDIs) from real-world prescriptions in a tertiary care hospital. Methods: We analyzed 500 randomly selected prescriptions from a hospital database, identifying 1133 unique drug pairs. Each pair was checked for potential interactions using all three platforms. We compared how often DDIs were detected, their severity ratings, and agreement between tools using Cohen’s kappa for concordance. Finding: Polypharmacy, defined as five or more drugs, was present in 23.8% of prescriptions, with an average of 6.3 drugs per patient. Polypharmacy was strongly linked to severe DDIs, showing nearly a threefold increased risk. Drugs.com identified the highest number of DDIs (21%), followed by Lexidrug (19.6%) and Medscape (16.2%). Severity ratings varied, and agreement between the tools was moderate (κ = 0.47–0.50). Conclusion: There is notable variation in detecting and classifying major DDIs among these common tools. Standardizing databases and interaction definitions is important. Meanwhile, clinicians should use multiple checkers alongside their clinical judgment to ensure safer prescribing when managing patients on many drugs.