Abstract
INTRODUCTION: Drug-drug interactions (DDIs) remain a significant but often overlooked threat to patient safety. While Pharmacists are expected to play a critical role in identifying and preventing DDIs, real-world practice may not reflect this responsibility. This study aimed to assess the gap between community Pharmacists' DDI knowledge and their actual dispensing practices in Western Saudi Arabia. METHODS: A sequential explanatory mixed-methods study was conducted between September and November 2025 among 356 licensed community Pharmacists in Makkah, Jeddah, Madinah, and Taif. The quantitative phase involved a validated, structured questionnaire evaluating Pharmacists' knowledge and self-reported practices regarding DDIs. This was followed by a qualitative observational phase involving 134 unannounced simulated patient (SP) visits, each presenting one of four predefined high-risk DDI scenarios (ibuprofen-furosemide, omeprazole-clopidogrel, fluconazole-phenytoin, and phenytoin-warfarin). Statistical analyses included descriptive statistics, non-parametric group comparisons (Wilcoxon and Kruskal-Wallis tests), multivariable linear regression, and Fisher's exact test, conducted using RStudio (p < 0.05). RESULTS: Survey findings demonstrated moderate to high theoretical DDI awareness, with 62-79% of Pharmacists correctly identifying major interaction pairs. Pharm. D. graduates achieved higher knowledge scores than B. Pharm graduates (median 5.0 vs. 4.0; p < 0.001). However, simulated visits revealed a substantial practice gap: only 15% of Pharmacists identified the DDI in real-time, and approximately 75% took no corrective action. Most encounters lasted less than one minute, and over 80% of interacting medications were dispensed without inquiry or reference checking. CONCLUSION: Despite adequate theoretical knowledge, community Pharmacists demonstrated limited real-world application of DDI management. This knowledge-practice gap poses a patient safety concern and underscores the need for system-level interventions, including decision-support tools, workflow optimization, and strengthened prescriber-Pharmacist communication.