{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T02:56:50Z","timestamp":1780887410529,"version":"3.54.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fenofibric acid is a small-molecule fibrate that functions as an agonist of peroxisome proliferator-activated receptor alpha (PPAR\u03b1) and serves as an inhibitor of liver fatty acid-binding protein. It is primarily prescribed for the management of hyperlipidemia, including conditions such as hypercholesterolemia and hypertriglyceridemia. As a lipid-lowering agent, a comprehensive understanding of the real-world safety profile of fenofibric acid is essential to ensure its safe and effective use in clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study utilizes four disproportionality analysis methods to investigate adverse event (AE) reports related to fenofibric acid in the WHO VigiAccess and FDA Adverse Event Reporting System (FAERS) databases, thereby providing robust scientific evidence for evaluating the real-world safety of fenofibric acid. Additionally, the study applies the Weibull distribution to estimate the timing of adverse event occurrences. The study investigates the relationship between adverse event reports and gender via gender-stratified analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This study retrieved 323 adverse event reports from WHO VigiAccess and 1,970 reports from FAERS. Drug-related signals were detected in 23 and 26 System Organ Class levels in the WHO VigiAccess and FAERS datasets, respectively. The study results confirmed known adverse reactions of fenofibric acid, including renal impairment, hepatobiliary toxicity, pancreatitis, and allergic reactions. Additionally, several potential adverse effects were identified, including gout, hypoglycemia, prothrombin time prolonged, photosensitivity reactions, rash, blood creatine and creatinine increased, blood creatine phosphokinase increased, myalgia, muscle fatigue, pain in extremity, joint pain and headache. The findings further underscore the importance of monitoring adverse events during the first 3 months of fenofibric acid use. The findings also highlight that closer attention to adverse events among female patients may have important clinical implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In addition to the known adverse reactions, this study has identified numerous potential adverse drug reactions associated with fenofibric acid. Although these findings require further validation through subsequent clinical trials, they provide valuable safety information for clinicians to consider when evaluating adverse effects in patients treated with fenofibric acid.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1702197","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T06:24:19Z","timestamp":1762496659000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Assessing the real-world safety of fenofibric acid for hyperlipidemia: results from WHO-VigiAccess and FAERS databases"],"prefix":"10.3389","volume":"12","author":[{"given":"Yaxing","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jidang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruonan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuepin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingli","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/b978-0-12-801401-1.00004-9","article-title":"Metabolomics in dyslipidemia.","volume":"66","author":"Chen","year":"2014","journal-title":"Adv Clin Chem"},{"key":"B2","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1093\/oxfordjournals.bmb.a072449","article-title":"Primary hyperlipidaemia.","volume":"46","author":"Thompson","year":"1990","journal-title":"Br Med Bull"},{"key":"B3","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S0889-8529(18)30324-4","article-title":"Acquired hyperlipidemia (secondary dyslipoproteinemias).","volume":"19","author":"Chait","year":"1990","journal-title":"Endocrinol Metab Clin North Am."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1093\/eurheartj\/8.suppl_e.3","article-title":"The pathology of atherosclerosis with particular reference to the effects of hyperlipidaemia.","volume":"8","author":"Woolf","year":"1987","journal-title":"Eur Heart J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/s0163-7258(98)00018-7","article-title":"Lipid-lowering drugs in the management of hyperlipidaemia.","volume":"79","author":"Bhatnagar","year":"1998","journal-title":"Pharmacol Ther"},{"key":"B6","first-page":"891","article-title":"Classification of hyperlipidaemias and hyperlipoproteinaemias.","volume":"43","author":"Beaumont","year":"1970","journal-title":"Bull World Health Organ."},{"key":"B7","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/j.1365-2036.2005.02591.x","article-title":"Review article: hyperlipidaemia and cardiovascular risk.","volume":"22","author":"Bertolotti","year":"2005","journal-title":"Aliment Pharmacol Ther"},{"key":"B8","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s11883-010-0117-4","article-title":"Hyperlipidemia and primary prevention of stroke: Does risk factor identification and reduction really work?","volume":"12","author":"Lewis","year":"2010","journal-title":"Curr Atheroscler Rep"},{"key":"B9","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1212\/wnl.18.9.883","article-title":"Neurological manifestations in hyperlipidemia.","volume":"18","author":"Aarli","year":"1968","journal-title":"Neurology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1542\/peds.65.3.674","article-title":"Hyperlipidemia screening is worthwhile.","volume":"65","author":"Freis","year":"1980","journal-title":"Pediatrics."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1093\/oxfordjournals.bmb.a072439","article-title":"Treatment of hyperlipidaemia.","volume":"46","author":"Illingworth","year":"1990","journal-title":"Br Med Bull"},{"key":"B12","doi-asserted-by":"publisher","first-page":"69S","DOI":"10.1016\/s0002-9343(98)00215-0","article-title":"A perspective on hyperlipidemia: concepts of management in the prevention of coronary artery disease.","volume":"105","author":"Amsterdam","year":"1998","journal-title":"Am J Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1146\/annurev.me.41.020190.002351","article-title":"Treatment of hyperlipidemia.","volume":"41","author":"Kane","year":"1990","journal-title":"Annu Rev Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4","DOI":"10.15212\/CVIA.2023.0004","article-title":"Lowering of blood lipid levels with a combination of pitavastatin and ezetimibe in patients with coronary heart disease: A meta-analysis.","volume":"7","author":"Cai","year":"2023","journal-title":"J CVIA"},{"key":"B15","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.biochi.2016.12.019","article-title":"The role and regulation of the peroxisome proliferator activated receptor alpha in human liver.","volume":"136","author":"Kersten","year":"2017","journal-title":"Biochimie"},{"key":"B16","doi-asserted-by":"publisher","first-page":"5344","DOI":"10.1021\/jm801349e","article-title":"Probing the fibrate binding specificity of rat liver fatty acid binding protein.","volume":"52","author":"Chuang","year":"2009","journal-title":"J Med Chem"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1194\/jlr.R056705","article-title":"Recent insights into the biological functions of liver fatty acid binding protein 1.","volume":"56","author":"Wang","year":"2015","journal-title":"J Lipid Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.4021\/cr270w","article-title":"Review of currently available fenofibrate and fenofibric acid formulations.","volume":"4","author":"Ling","year":"2013","journal-title":"Cardiol Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1097\/JS9.0000000000002194","article-title":"Systematic analysis of sugammadex-related adverse drug reaction signals using FAERS database.","volume":"111","author":"Liu","year":"2024","journal-title":"Int J Surg"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1111\/apt.16601","article-title":"Bevacizumab and gastrointestinal perforations: a review from the FDA Adverse Event Reporting System (FAERS) database.","volume":"54","author":"Wichelmann","year":"2021","journal-title":"Aliment Pharmacol Ther"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1431562","DOI":"10.3389\/fphar.2024.1431562","article-title":"Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration\u2019s adverse event reporting system databases.","volume":"15","author":"Liang","year":"2024","journal-title":"Front Pharmacol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1310286","DOI":"10.3389\/fphar.2024.1310286","article-title":"A real-world study of antifibrotic drugs-related adverse events based on the United States food and drug administration adverse event reporting system and VigiAccess databases.","volume":"15","author":"He","year":"2024","journal-title":"Front Pharmacol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA Adverse Event Reporting System.","volume":"10","author":"Sakaeda","year":"2013","journal-title":"Int J Med Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s002280050466","article-title":"A Bayesian neural network method for adverse drug reaction signal generation.","volume":"54","author":"Bate","year":"1998","journal-title":"Eur J Clin Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/pds.677","article-title":"Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports.","volume":"10","author":"Evans","year":"2001","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B26","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s40264-019-00899-y","article-title":"Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase\u00ae.","volume":"43","author":"Vogel","year":"2020","journal-title":"Drug Saf"},{"key":"B27","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/5584_2020_534","article-title":"Hypoglycaemia.","volume":"1307","author":"Muneer","year":"2021","journal-title":"Adv Exp Med Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1210\/endrev\/bnaa017","article-title":"Glycemic monitoring and management in advanced chronic kidney disease.","volume":"41","author":"Galindo","year":"2020","journal-title":"Endocr Rev"},{"key":"B29","doi-asserted-by":"publisher","first-page":"829","DOI":"10.3748\/wjg.v19.i6.829","article-title":"Diagnosis and management of insulinoma.","volume":"19","author":"Okabayashi","year":"2013","journal-title":"World J Gastroenterol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/s0889-8529(05)70088-8","article-title":"Drug-induced hypoglycemia.","volume":"28","author":"Marks","year":"1999","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B31","doi-asserted-by":"publisher","first-page":"232","DOI":"10.3390\/pharmaceutics14020232","article-title":"In silico searching for alternative lead compounds to treat type 2 diabetes through a QSAR and molecular dynamics study.","volume":"14","author":"Cabrera","year":"2022","journal-title":"Pharmaceutics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1016\/S0140-6736(21)00569-9","article-title":"Gout.","volume":"397","author":"Dalbeth","year":"2021","journal-title":"Lancet"},{"key":"B33","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1146\/annurev-physiol-021113-170343","article-title":"The molecular physiology of uric acid homeostasis.","volume":"77","author":"Mandal","year":"2015","journal-title":"Annu Rev Physiol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1161\/ATVBAHA.113.302926","article-title":"Effects of fenofibric acid on carotid intima-media thickness in patients with mixed dyslipidemia on atorvastatin therapy: randomized, placebo-controlled study (FIRST).","volume":"34","author":"Davidson","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1080\/00498254.2017.1306760","article-title":"The effect of fenofibric acid on the pharmacokinetics and pharmacodynamics of warfarin in rats.","volume":"48","author":"Guo","year":"2018","journal-title":"Xenobiotica"},{"key":"B36","doi-asserted-by":"publisher","first-page":"30","DOI":"10.15212\/CVIA.2023.0030","article-title":"Comparison of the safety and efficacy of warfarin versus rivaroxaban in northern chinese patients with different CHA2DS2-VASc Scores: A Retrospective Cohort Study.","volume":"8","author":"Xu","year":"2023","journal-title":"J CVIA"},{"key":"B37","doi-asserted-by":"publisher","first-page":"876695","DOI":"10.3389\/falgy.2022.876695","article-title":"Drug-induced photosensitivity: clinical types of phototoxicity and photoallergy and pathogenetic mechanisms.","volume":"3","author":"Di Bartolomeo","year":"2022","journal-title":"Front Allergy"},{"key":"B38","first-page":"580","article-title":"Drug-induced photosensitivity.","volume":"12","author":"Allen","year":"1993","journal-title":"Clin Pharm"},{"key":"B39","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/s1085-5629(99)80026-1","article-title":"Phototoxicity and photoallergy.","volume":"18","author":"Epstein","year":"1999","journal-title":"Semin Cutan Med Surg"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.2337\/dc10-0357","article-title":"The effects of fenofibric acid alone and with statins on the prevalence of metabolic syndrome and its diagnostic components in patients with mixed dyslipidemia.","volume":"33","author":"Bays","year":"2010","journal-title":"Diabetes Care"},{"key":"B41","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/0021-9150(81)90043-5","article-title":"Fenofibrate therapy of hyperlipoproteinaemia. A dose-response study and a comparison with clofibrate.","volume":"38","author":"R\u00f6ssner","year":"1981","journal-title":"Atherosclerosis"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1016\/S0140-6736(05)67667-2","article-title":"Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.","volume":"366","author":"Keech","year":"2005","journal-title":"Lancet"},{"key":"B43","doi-asserted-by":"publisher","first-page":"101015","DOI":"10.1016\/j.disamonth.2020.101015","article-title":"Rhabdomyolysis.","volume":"66","author":"Cabral","year":"2020","journal-title":"Dis Mon"},{"key":"B44","doi-asserted-by":"publisher","first-page":"8056","DOI":"10.3390\/ijms21218056","article-title":"PPARs and microbiota in skeletal muscle health and wasting.","volume":"21","author":"Manickam","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.biochi.2016.11.010","article-title":"Roles of peroxisome proliferator-activated receptor \u03b2\/\u03b4 in skeletal muscle physiology.","volume":"136","author":"Manickam","year":"2017","journal-title":"Biochimie"},{"key":"B46","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.atherosclerosis.2008.09.027","article-title":"Efficacy and safety of ABT-335 (fenofibric acid) in combination with rosuvastatin in patients with mixed dyslipidemia: a phase 3 study.","volume":"204","author":"Jones","year":"2009","journal-title":"Atherosclerosis"},{"key":"B47","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.ahj.2010.06.045","article-title":"Efficacy and safety of fenofibric acid in combination with atorvastatin and ezetimibe in patients with mixed dyslipidemia.","volume":"160","author":"Jones","year":"2010","journal-title":"Am Heart J"},{"key":"B48","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.ahj.2008.08.027","article-title":"Efficacy and safety of ABT-335 (fenofibric acid) in combination with simvastatin in patients with mixed dyslipidemia: a phase 3, randomized, controlled study.","volume":"157","author":"Mohiuddin","year":"2009","journal-title":"Am Heart J"},{"key":"B49","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s10557-010-6266-4","article-title":"Efficacy and safety of rosuvastatin 5 mg in combination with fenofibric acid 135 mg in patients with mixed dyslipidemia - a phase 3 study.","volume":"24","author":"Roth","year":"2010","journal-title":"Cardiovasc Drugs Ther"},{"key":"B50","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.clinthera.2011.05.047","article-title":"Single-dose bioequivalence of 105-mg fenofibric acid tablets versus 145-mg fenofibrate tablets under fasting and fed conditions: a report of two phase I, open-label, single-dose, randomized, crossover clinical trials.","volume":"33","author":"Godfrey","year":"2011","journal-title":"Clin Ther"},{"key":"B51","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13293-022-00420-8","article-title":"Considerations and challenges for sex-aware drug repurposing.","volume":"13","author":"Fisher","year":"2022","journal-title":"Biol Sex Differ"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e00541","DOI":"10.1002\/prp2.541","article-title":"Individualized medicine: sex, hormones, genetics, and adverse drug reactions.","volume":"7","author":"Moyer","year":"2019","journal-title":"Pharmacol Res Perspect"},{"key":"B53","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s40360-023-00727-1","article-title":"Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes.","volume":"25","author":"Fisher","year":"2024","journal-title":"BMC Pharmacol Toxicol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1702197\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T06:24:19Z","timestamp":1762496659000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1702197\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,7]]},"references-count":53,"alternative-id":["10.3389\/fmed.2025.1702197"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1702197","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,7]]},"article-number":"1702197"}}