The novel Medication Safety Risk Score quantifies clinically and economically meaningful polypharmacy adverse effects based on pharmacokinetics, pharmacodynamics, chronopharmacology, and pharmacogenomics factors. The Medication Risk Score is unique in its ability to compute aggregated and simultaneous anticholinergic cognitive burden (ACB), sedative burden (S.B.), drug-induced Long QT Syndrome (LQTS) burden, and competitive inhibition (CYP450) burden (CIB) risks from a patient’s medication, OTC & supplement regimen. The presentation will include sharing several recently published case studies based on the results of a CMS Center for Medicare & Medicaid Innovation Part D Enhanced Medication Therapy Management Innovation Model, and an in silico clinical trial study to determine medication-induced premature death.