Polypharmacy and drug-drug interactions in long-term care facilities residents: findings from the Italian Prescription Day Project

Background: Medication prescribing in long-term care facilities (LTCFs) is characterized by widespread polypharmacy and frequent exposure to potentially clinically relevant drug-drug interactions (DDIs). Methods: Data from the Italian Prescription Day in LTCFs 2024, a national multicenter point-prevalence study conducted in 82 LTCFs, were analyzed. Prescriptions were classified using the Anatomical Therapeutic Chemical system, and DDIs were identified using an international consensus list. Resident-level variables were assessed using validated tools, and associations with DDI burden were examined using univariate mixed-effects Poisson regression models. Facility-level organizational characteristics were described by center-level DDI burden. Results: The analysis included 3174 residents (mean age 84.8 years; 74.1% women), with a mean of 7.7 prescribed drugs. Drugs acting on the nervous system, alimentary tract and metabolism, and cardiovascular system were most frequently prescribed; furosemide, paracetamol, pantoprazole, quetiapine, and macrogol were the most commonly used active substances. Overall, 42.2% of residents were exposed to at least one potentially clinically relevant DDI, most commonly involving centrally acting drugs, cumulative anticholinergic burden, serotonergic combinations, and potassium-related interactions. Higher DDI burden was associated with greater pharmacological complexity, depression, sleep disorders, cardiopulmonary disease, and behavioral and psychological symptoms of dementia, whereas older age, severe cognitive impairment, malnutrition, and dysphagia were associated with fewer DDIs. Facility-level and staffing characteristics showed limited differentiation, with assisted living facilities under-represented at higher DDI burden. Conclusions: Potentially clinically relevant DDIs are common in Italian LTCFs and are primarily associated with resident-level clinical complexity, highlighting targets for medication review and deprescribing to improve medication safety.