Agreement of Different Drug-Drug Interaction Checkers for Proton Pump Inhibitors.

Importance: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, potentially interacting with a large number of medicines, especially among older patients with multimorbidity and polypharmacy. Beyond summary of product characteristics (SPCs), interaction checkers (ICs) are routinely used tools to help clinicians in medication review interventions. Objective: To assess the consistency of information on drugs potentially interacting with PPIs as reported in their SPCs and different ICs. Design, Setting, and Participants: This cross-sectional study was conducted using data from SPCs for 5 PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) and 5 ICs (ie, INTERCheck WEB, Micromedex, Lexicomp, Epocrates, and drugs.com). Information from the SPCs and the ICs were extracted between July 15 and 30, 2023. Main Outcomes and Measures: The main outcome was the level of agreement among SPCs and the 5 ICs in identifying drugs potentially interacting with PPIs and attributing drug-drug interaction (DDI) severity categories. The level of agreement was computed using Gwet AC1 statistic on the 5 ICs and by comparing 4-sets and 2-sets of ICs. As a sensitivity analysis, the level of agreement in listing PPI-related DDIs was evaluated using Cohen κ and Fleiss κ coefficients. Results: Considering SPCs and the 5 ICs, a total of 518 potentially interacting drugs with omeprazole were reported, 455 for esomeprazole, 433 for lansoprazole, 421 for pantoprazole, and 405 for rabeprazole. As compared with the ICs, the SPCs reported a much smaller number of drugs potentially interacting with PPIs, with proportions ranging from 2.7% (11 potentially interacting drugs) for rabeprazole to 7.6% (33 potentially interacting drugs) for lansoprazole of the total identified drugs at risk of interaction with a PPI. The overall level of agreement among the 5 ICs for identifying potential interactions was poor (from 0.23 [95% CI, 0.21-0.25] for omeprazole to 0.27 [95% CI, 0.24-0.29] for pantoprazole and 0.27 [95% CI, 0.25-0.29] for rabeprazole). Similarly, the level of agreement was low in 4-set and 2-set analyses as well as when restricting the analysis to the potential DDIs identified as severe (range, 0.30-0.32). Conclusions and Relevance: This cross-sectional study found significant disagreement among different ICs and SPCs, highlighting the need to focus on standardizing DDI databases. Therefore, to ensure evaluation and prevention of clinically relevant DDIs, it is recommended to revise multiple ICs and consult with specialists, such as clinical pharmacologists, particularly for patients with complex medical conditions.

Clinical impact of medication review and deprescribing in older inpatients: A systematic review and meta-analysis.

BACKGROUND: Polypharmacy is a primary risk factor for the prescription of potentially inappropriate medications (PIMs), drug-drug interactions (DDIs), and ultimately, adverse drug reactions (ADRs). Medication review and deprescribing represent effective strategies to simplify therapeutic regimens, minimize risks, and reduce PIM prescriptions. This systematic review and meta-analysis of experimental and observational studies aimed to evaluate the impact of different medication review and deprescribing interventions in hospitalized older patients. METHODS: Experimental and observational prospective cohort studies evaluating the clinical effects of medication review and deprescribing strategies in older hospitalized patients were searched in the bibliographic databases, PubMed, Embase, and Scopus, from inception until January 8, 2024. A narrative synthesis of the results was provided, along with a meta-analysis of dichotomous data (i.e., re-hospitalizations and mortality). RESULTS: Overall, 21 randomized controlled trials, 7 non-randomized interventional studies, and 2 prospective cohort studies were included in the systematic review. Of these, 14 (46.7%) assessed medication appropriateness as the primary outcome, while the remaining evaluated clinical outcomes (e.g., length of hospital stay, hospital readmissions, emergency department visits, and incidence of ADRs) and/or quality of life. The meta-analysis revealed a slight but statistically significant 8% reduction in hospital readmissions (HR: 0.92; 95% CI: 0.85-0.99) following medication review and deprescribing, but no significant impact on mortality (HR: 0.98; 95% CI: 0.96-1.00). Of the 30 included studies, 21 were considered at high risk of bias, mostly due to potential deviations from intended interventions and randomization processes. The remaining nine studies had "some concerns" (eight studies) or were considered at "low" risk of bias (one study). CONCLUSION: Medication review and deprescribing are associated with potential benefits in reducing hospital readmission rates among hospitalized older patients, particularly through the reduction of PIM prescriptions. The integration of thorough medication review and deprescribing protocols in hospital settings may improve post-discharge outcomes and reduce overall healthcare costs.