Medication Burden as a Clinical Risk Signal: Prospective Linkage of Polypharmacy, Drug–Drug Interactions and Adverse Drug Reactions with Outcomes in Multimorbid Medical Inpatients

Abstract

Background: Multimorbidity frequently necessitates multiple medications, increasing the risk of drug–drug interactions (DDIs), adverse drug reactions (ADRs), and adverse clinical outcomes. This study prospectively evaluated medication burden and its consequences among General Medicine inpatients. Methods: A prospective observational study was conducted at GSL Medical College from November 2025 to May 2026. Adult multimorbid inpatients were followed from admission to discharge. Polypharmacy, potential and clinically relevant DDIs, ADRs, and outcomes were assessed using structured medication review and standard causality, severity, and preventability tools. Results: Among 240 patients, mean age was 58.7±15.2 years and 72.5% had polypharmacy; 26.3% had excessive polypharmacy. Potential DDIs occurred in 62.9%, with 73.8% of 389 interactions graded moderate. ADRs occurred in 22.5%. Excessive polypharmacy (aOR 3.42, 95% CI 1.73–6.78), clinically relevant DDIs (aOR 2.81, 95% CI 1.25–6.31), and renal dysfunction (aOR 2.17, 95% CI 1.08–4.36) independently predicted ADRs. ADRs were associated with longer hospitalization and increased ICU transfer. Conclusion: Medication burden, clinically relevant DDIs, and renal impairment identified patients at greatest risk of ADRs. Prospective medication reconciliation, targeted interaction surveillance, renal dose review, and deprescribing may improve safety in multimorbid medical inpatients. The findings support integrating systematic medication-safety review into routine inpatient General Medicine practice for high-risk patients. Keywords: Adverse drug reactions; Drug–drug interactions; Medication safety; Multimorbidity; Polypharmacy.