{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T12:26:15Z","timestamp":1788006375977,"version":"build-2784847793"},"reference-count":253,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Drug-induced adverse events remain a major challenge in modern pharmacotherapy, particularly with the increasing use of targeted therapies, biologics, and combination regimens. In clinical practice, toxicity is often difficult to predict, interpret, and manage because adverse events arise from complex interactions between drug mechanisms, patient susceptibility, and treatment context. This review provides a clinically oriented framework for understanding drug-induced adverse events across multiple levels. We first summarize key mechanistic drivers, including pathway perturbation, off-target effects, metabolic and mitochondrial dysfunction, and immune dysregulation. We then discuss how these mechanisms translate into organ-specific toxicity patterns involving the liver, heart, kidney, nervous system, and immune system, which represent the most common clinical presentations. In addition, we examine how safety profiles are defined and refined through different layers of evidence, including randomized clinical trials, meta-analyses, and real-world pharmacovigilance data. These complementary evidence sources are essential for identifying both common and rare adverse events, particularly those that emerge after broader clinical use. Importantly, this review highlights practical considerations for clinical risk assessment and management. We discuss key factors influencing toxicity risk, including patient comorbidity, polypharmacy, and baseline organ function, as well as the role of dynamic monitoring, biomarkers, and early signal detection. Emphasis is placed on translating mechanistic insight into actionable strategies for prevention, early recognition, and individualized management of adverse events. Overall, drug safety should be viewed as a dynamic and context-dependent process. Integrating mechanistic understanding with clinical evidence and real-world data can improve risk prediction and support more effective and personalized pharmacotherapy.<\/jats:p>","DOI":"10.3389\/fphar.2026.1857708","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:38:10Z","timestamp":1783661890000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Drug-induced adverse events in modern pharmacotherapy: mechanisms, clinical manifestations, and implications for risk assessment and management"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhangyurong","family":"Chen","sequence":"first","affiliation":[{"name":"College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University","place":["Fuzhou, China"]},{"name":"Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, Xiamen University","place":["Xiamen, China"]},{"name":"Fujian Provincial Key Laboratory of Featured Biochemical and Chemical Materials, Ningde Normal University","place":["Ningde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University","place":["Fuzhou, China"]},{"name":"Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University","place":["Fuzhou, China"]},{"name":"Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyue","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University","place":["Fuzhou, China"]},{"name":"Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaicong","family":"Cai","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University","place":["Fuzhou, China"]},{"name":"Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, Xiamen University","place":["Xiamen, China"]},{"name":"Fujian Provincial Key Laboratory of Featured Biochemical and Chemical Materials, Ningde Normal University","place":["Ningde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.biopha.2017.10.141","article-title":"Bergenia ciliata: a comprehensive review of its traditional uses, phytochemistry, pharmacology and safety","volume":"97","author":"Ahmad","year":"2018","journal-title":"Biomed. and Pharmacother."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.2174\/1871527321666220614121439","article-title":"Smartphone addiction among students and its harmful effects on mental health, oxidative stress, and neurodegeneration towards future modulation of anti-addiction therapies: a comprehensive survey based on SLR, research questions, and network visualization techniques","volume":"22","author":"Akhtar","year":"2023","journal-title":"Cns and Neurological Disorders-drug Targets"},{"key":"B3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.2147\/DHPS.S28801","article-title":"Clinical use of anti-TNF therapy and increased risk of infections","volume":"5","author":"Ali","year":"2013","journal-title":"Drug Healthc. 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