REAL-WORLD SAFETY OF XANOMELINE/TROSPIUM CHLORIDE IN SCHIZOPHRENIA MANAGEMENT
Author(s)
Chisom D. Eze, B.Pharm1, Mohammad A. Al-Mamun, PhD2;
1West Virginia University, Student, Morgantown, WV, USA, 2Binghamton University, Systems Science and Industrial Engineering, Binghamton, NY, USA
1West Virginia University, Student, Morgantown, WV, USA, 2Binghamton University, Systems Science and Industrial Engineering, Binghamton, NY, USA
OBJECTIVES: Xanomeline/trospium chloride reduced the positive and negative syndrome scale (PANSS) score by 5.9-17.4 points across trials. However, its safety profile in routine clinical use remains inadequately explored. We aimed to assess the real-world safety of xanomeline/trospium chloride compared to an atypical antipsychotic (risperidone).
METHODS: We utilized the FDA Adverse events Reporting System (FAERS) data from January 2024 to June 2025. Reports with xanomeline/trospium chloride or risperidone as the primary suspect drug were extracted. Potential adverse events (AEs) signals were detected by calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) from Bayesian confidence propagation neural network, and empirical bayes geometric mean (EBGM) from multi-item gamma Poisson shrinker. A lexicon-based natural language processing pipeline was developed to detect clinical trials-published AE (5 publications) and compared to FAERS-reported AEs.
RESULTS: Of 801 Xanomeline-associated reports, most common AEs were nausea (10.65%), vomiting (9.70%), and constipation (3.59%). Of 5,986 risperidone-associated reports, gynecomastia (6.82%), weight increase (3.27%), and emotional disorder (3.01%) were reported more. Comparatively, nausea and vomiting were reported more for xanomeline, while weight increase, tremor and somnolence were higher for risperidone. Risperidone-associated reports were more often associated with mortality (3.60%) and hospitalization (22.20%). Strong AE signals for nausea (R0R = 26.25 (19.36-35.61), PRR (chi square) = 20.92 (875.13), 25% IC = 2.58, 5% EBGM = 5.32) and urinary retention (R0R = 29.73 (16.23-54.47), PRR (chi square) = 27.93 (278.87), 25% IC = 2.58, 5% EBGM = 4.88) were detected for xanomeline. Similar AEs were reported in FAERs and clinical trials for xanomeline, but AEs including urinary retention, blurred vision, were reported in FAERS but not clinical trials.
CONCLUSIONS: Real-world safety profile of xanomeline/trospium chloride differed from risperidone. There was concordance between FAERS- and trial-reported AEs for xanomeline/trospium chloride. However, the FAERS analysis revealed additional AEs which were not detected the NLP analysis.
METHODS: We utilized the FDA Adverse events Reporting System (FAERS) data from January 2024 to June 2025. Reports with xanomeline/trospium chloride or risperidone as the primary suspect drug were extracted. Potential adverse events (AEs) signals were detected by calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) from Bayesian confidence propagation neural network, and empirical bayes geometric mean (EBGM) from multi-item gamma Poisson shrinker. A lexicon-based natural language processing pipeline was developed to detect clinical trials-published AE (5 publications) and compared to FAERS-reported AEs.
RESULTS: Of 801 Xanomeline-associated reports, most common AEs were nausea (10.65%), vomiting (9.70%), and constipation (3.59%). Of 5,986 risperidone-associated reports, gynecomastia (6.82%), weight increase (3.27%), and emotional disorder (3.01%) were reported more. Comparatively, nausea and vomiting were reported more for xanomeline, while weight increase, tremor and somnolence were higher for risperidone. Risperidone-associated reports were more often associated with mortality (3.60%) and hospitalization (22.20%). Strong AE signals for nausea (R0R = 26.25 (19.36-35.61), PRR (chi square) = 20.92 (875.13), 25% IC = 2.58, 5% EBGM = 5.32) and urinary retention (R0R = 29.73 (16.23-54.47), PRR (chi square) = 27.93 (278.87), 25% IC = 2.58, 5% EBGM = 4.88) were detected for xanomeline. Similar AEs were reported in FAERs and clinical trials for xanomeline, but AEs including urinary retention, blurred vision, were reported in FAERS but not clinical trials.
CONCLUSIONS: Real-world safety profile of xanomeline/trospium chloride differed from risperidone. There was concordance between FAERS- and trial-reported AEs for xanomeline/trospium chloride. However, the FAERS analysis revealed additional AEs which were not detected the NLP analysis.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EPH102
Topic
Epidemiology & Public Health
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Rare & Orphan Diseases