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This framework is coupled with a systems pharmacology approach for automated biological plausibility assessment. Integrating statistical and biological evidence, our method achieves a 16.5% improvement (AUC: from 0.620 to 0.722) with drug\u2010target\u2010adverse event associations, 16.0% (AUC: from 0.580 to 0.673) with drug enzyme, and 15.0% (AUC: from 0.568 to 0.653) with drug transporter information. Applying this approach to detect potential DDI signals of QT prolongation and rhabdomyolysis within the FDA Adverse Event Reporting System (FAERS), we emphasize the significance of systems pharmacology in enhancing statistical signal detection in pharmacovigilance. 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