| アブストラクト | BACKGROUND: alpha1-Adrenergic blockers are widely used in older patients, yet nervous system adverse events associated with these agents are often considered nonspecific and remain insufficiently characterized at the population level. OBJECTIVES: To evaluate nervous system adverse events associated with alpha1-adrenergic blockers using real-world pharmacovigilance data, assess drug-specific and patient-specific risks, and translate findings into clinically interpretable risk profiles. DESIGN: A retrospective, observational pharmacovigilance study. METHODS: We conducted an integrated pharmacovigilance analysis using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) as the discovery dataset and the Japanese Adverse Drug Event Report (JADER) database for external validation. Hierarchical signal detection within the Medical Dictionary for Regulatory Activities (MedDRA) nervous system organ class was used to construct a data-driven composite endpoint. Multivariable logistic regression with least absolute shrinkage and selection operator (LASSO)-guided feature selection estimated adjusted associations for five alpha1-adrenergic blockers while accounting for age, sex, and major comorbidities. Model performance and calibration were evaluated in JADER. Individualized risk portraits were generated across clinically relevant patient profiles. RESULTS: Several alpha1-adrenergic blockers demonstrated significant and heterogeneous associations with nervous system adverse events in FAERS after adjustment. External validation in JADER showed consistent effect directions for drugs with sufficient exposure and acceptable calibration. Risk portrait analyses revealed marked risk stratification by age and comorbidity burden, with the highest predicted reporting probability observed among elderly patients with multiple comorbidities. CONCLUSION: This integrated pharmacovigilance framework provides a structured and clinically interpretable assessment of nervous system safety among alpha1-adrenergic blockers, highlighting the importance of agent-specific and patient-specific risk evaluation. |
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| ジャーナル名 | Therapeutic advances in drug safety |
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| Pubmed追加日 | 2026/5/4 |
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| 投稿者 | Hai, Xin; Huang, Lulu |
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| 組織名 | Department of Urology, Union Hospital, Tongji Medical College, Huazhong;University of Science and Technology, Wuhan 430022, China.;University of Science and Technology, Wuhan, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42077262/ |
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