{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T18:39:56Z","timestamp":1755801596701,"version":"3.44.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>This study aims to assess the adverse events (AEs) and safety profile of omeprazole, a widely used proton pump inhibitor (PPI) for acid-related diseases. Despite being a first-line treatment, its overuse due to easy accessibility and lack of public awareness about usage guidelines may lead to potential side effects, necessitating a reassessment of its safety.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We extracted 119,159 adverse event reports (AERs) related to omeprazole from the FDA Adverse Event Reporting System (FAERS) database, covering data from Q1 2004 to Q4 2023. A disproportionality analysis was performed to evaluate indications, concomitant medication use, and safety.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Omeprazole was commonly prescribed for gastroesophageal reflux disease (GERD), dyspepsia, peptic ulcers, and gastritis. It was frequently used with drugs like aspirin, lisinopril, furosemide, atorvastatin, and metoprolol. Notably, renal and urinary disorders showed strong positive signals, including chronic kidney disease, acute kidney injury, and renal failure, with statistically significant disproportionality measures. The study also identified adverse reactions not listed on drug labels, such as hyperparathyroidism secondary and intentional product misuse.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our findings provide new insights into the safety of omeprazole in real-world clinical settings, highlighting novel adverse events and offering evidence for safer clinical use.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0330509","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T17:37:30Z","timestamp":1755711450000},"page":"e0330509","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Updating understanding of real-world adverse events associated with omeprazole"],"prefix":"10.1371","volume":"20","author":[{"given":"Jijun","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9594-9978","authenticated-orcid":true,"given":"Jie","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"issue":"9337","key":"pone.0330509.ref001","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0140-6736(02)11030-0","article-title":"Peptic-ulcer disease","volume":"360","author":"FKL Chan","year":"2002","journal-title":"Lancet"},{"issue":"6","key":"pone.0330509.ref002","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1136\/gut.36.6.819","article-title":"Prevalence and incidence of peptic ulcer disease in a Danish County--a prospective cohort study","volume":"36","author":"SJ Rosenstock","year":"1995","journal-title":"Gut"},{"key":"pone.0330509.ref003","article-title":"Peptic Ulcer Disease and Related Disorders.","volume-title":"Harrison\u2019s Principles of Internal Medicine [Internet]","author":"JD. Valle","year":"2018","edition":"20"},{"issue":"7","key":"pone.0330509.ref004","first-page":"1005","article-title":"Peptic ulcer disease","volume":"76","author":"K Ramakrishnan","year":"2007","journal-title":"Am Fam Physician"},{"issue":"3","key":"pone.0330509.ref005","article-title":"Gastroesophageal Reflux Disease (GERD)","volume":"115","author":"DM Clarrett","year":"2018","journal-title":"Mo Med"},{"issue":"1","key":"pone.0330509.ref006","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1440-1746.2007.05249.x","article-title":"Asia-Pacific consensus on the management of gastroesophageal reflux disease: update","volume":"23","author":"KM Fock","year":"2008","journal-title":"J Gastroenterol Hepatol"},{"issue":"3","key":"pone.0330509.ref007","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1136\/gutjnl-2016-313589","article-title":"Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis","volume":"67","author":"LH Eusebi","year":"2018","journal-title":"Gut"},{"issue":"5","key":"pone.0330509.ref008","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/ajg.2013.71","article-title":"ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE)","volume":"108","author":"ES Dellon","year":"2013","journal-title":"Am J Gastroenterol"},{"issue":"3","key":"pone.0330509.ref009","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ajg.2012.444","article-title":"Guidelines for the diagnosis and management of gastroesophageal reflux disease","volume":"108","author":"PO Katz","year":"2013","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"pone.0330509.ref010","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1046\/j.1365-2036.2003.01756.x","article-title":"Direct comparative trials of the efficacy of proton pump inhibitors in the management of gastro-oesophageal reflux disease and peptic ulcer disease","volume":"18","author":"N Vakil","year":"2003","journal-title":"Aliment Pharmacol Ther"},{"issue":"8","key":"pone.0330509.ref011","article-title":"Pharmacological treatment of gastro-oesophageal reflux in children","volume":"8","author":"MP Tighe","year":"2023","journal-title":"Cochrane Database Syst Rev"},{"issue":"10","key":"pone.0330509.ref012","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1080\/17512433.2023.2252327","article-title":"Encouraging appropriate use of proton pump inhibitors: existing initiatives and proposals for the future","volume":"16","author":"A Mari","year":"2023","journal-title":"Expert Rev Clin Pharmacol"},{"issue":"11","key":"pone.0330509.ref013","article-title":"Proton pump inhibitor utilisation and potentially inappropriate prescribing analysis: insights from a single-centred retrospective study","volume":"10","author":"Y Liu","year":"2020","journal-title":"BMJ open"},{"issue":"5","key":"pone.0330509.ref014","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1038\/ajg.2009.80","article-title":"Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites","volume":"104","author":"JS Bajaj","year":"2009","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"pone.0330509.ref015","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/phar.1410","article-title":"Study of the association between hip fracture and acid-suppressive drug use in a UK primary care setting","volume":"34","author":"L Cea Soriano","year":"2014","journal-title":"Pharmacotherapy"},{"issue":"12","key":"pone.0330509.ref016","doi-asserted-by":"crossref","DOI":"10.2106\/JBJS.RVW.18.00029","article-title":"Proton pump inhibitors and bone health: what the orthopaedic surgeon needs to know","volume":"6","author":"SC Wagner","year":"2018","journal-title":"JBJS Rev"},{"issue":"6","key":"pone.0330509.ref017","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1016\/j.kint.2016.12.021","article-title":"Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury","volume":"91","author":"Y Xie","year":"2017","journal-title":"Kidney Int"},{"key":"pone.0330509.ref018","doi-asserted-by":"crossref","first-page":"1516449","DOI":"10.3389\/fphar.2025.1516449","article-title":"Safety evaluation of irinotecan: a real-world disproportionality analysis using FAERS and JADER databases during the time period 2004-2024","volume":"16","author":"S Lou","year":"2025","journal-title":"Front Pharmacol"},{"key":"pone.0330509.ref019","first-page":"37","article-title":"Extracting and standardizing medication information in clinical text \u2013 the MedEx-UIMA system","volume":"2014","author":"M Jiang","year":"2014","journal-title":"AMIA Jt Summits Transl Sci Proc"},{"issue":"7","key":"pone.0330509.ref020","doi-asserted-by":"crossref","first-page":"617","DOI":"10.2165\/00002018-200730070-00009","article-title":"Standardised MedDRA queries: their role in signal detection","volume":"30","author":"P Mozzicato","year":"2007","journal-title":"Drug Saf"},{"key":"pone.0330509.ref021","doi-asserted-by":"crossref","first-page":"101967","DOI":"10.1016\/j.eclinm.2023.101967","article-title":"Psychiatric disorders associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database","volume":"59","author":"C Zhou","year":"2023","journal-title":"EClinicalMedicine"},{"issue":"1","key":"pone.0330509.ref022","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40360-023-00702-w","article-title":"A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS)","volume":"24","author":"SP Zou","year":"2023","journal-title":"BMC Pharmacol Toxicol"},{"key":"pone.0330509.ref023","doi-asserted-by":"crossref","first-page":"1413709","DOI":"10.3389\/fphar.2024.1413709","article-title":"Safety assessment of neurokinin-1 receptor antagonist: real-world adverse event analysis from the FAERS database","volume":"15","author":"C Yang","year":"2024","journal-title":"Front Pharmacol"},{"issue":"3","key":"pone.0330509.ref024","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2165\/00002018-200326030-00003","article-title":"Quantitative methods in pharmacovigilance: focus on signal detection","volume":"26","author":"M Hauben","year":"2003","journal-title":"Drug Saf"},{"issue":"6","key":"pone.0330509.ref025","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1111\/j.1365-2044.2008.05861.x","article-title":"The effect of ranitidine versus proton pump inhibitors on gastric secretions: a meta-analysis of randomised control trials","volume":"64","author":"K Clark","year":"2009","journal-title":"Anaesthesia"},{"key":"pone.0330509.ref026","first-page":"259","article-title":"Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management","volume":"9","author":"W Li","year":"2013","journal-title":"Ther Clin Risk Manag"},{"issue":"11","key":"pone.0330509.ref027","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1093\/aje\/kwi325","article-title":"A systematic review and meta-analysis of the sex ratio for Barrett\u2019s esophagus, erosive reflux disease, and nonerosive reflux disease","volume":"162","author":"MB Cook","year":"2005","journal-title":"Am J Epidemiol"},{"issue":"5","key":"pone.0330509.ref028","doi-asserted-by":"crossref","DOI":"10.3748\/wjg.v22.i5.1800","article-title":"Gender difference in gastro-esophageal reflux diseases","volume":"22","author":"K Asanuma","year":"2016","journal-title":"World J Gastroenterol"},{"issue":"4","key":"pone.0330509.ref029","first-page":"332","article-title":"Proton pump inhibitors and statins: a possible interaction that favors low-density lipoprotein cholesterol reduction?","volume":"19","author":"F Barkas","year":"2015","journal-title":"Hippokratia"},{"key":"pone.0330509.ref030","first-page":"59","article-title":"Rhabdomyolysis secondary to drug interaction between atorvastatin, omeprazole, and dexamethasone","volume":"5","author":"S Elazzazy","year":"2012","journal-title":"Int Med Case Rep J"},{"issue":"10093","key":"pone.0330509.ref031","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S0140-6736(17)30770-5","article-title":"Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study","volume":"390","author":"L Li","year":"2017","journal-title":"Lancet"},{"issue":"2","key":"pone.0330509.ref032","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/ki.2014.294","article-title":"Clinical characteristics, causes and outcomes of acute interstitial nephritis in the elderly","volume":"87","author":"AK Muriithi","year":"2015","journal-title":"Kidney Int"},{"issue":"12","key":"pone.0330509.ref033","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1111\/j.1532-5415.2010.03194.x","article-title":"Late-onset omeprazole-associated acute interstitial nephritis","volume":"58","author":"N Ni","year":"2010","journal-title":"J Am Geriatr Soc"},{"issue":"1","key":"pone.0330509.ref034","doi-asserted-by":"crossref","first-page":"50","DOI":"10.12968\/hmed.2016.77.1.50","article-title":"Acute interstitial nephritis caused by two different proton pump inhibitors","volume":"77","author":"FJA Torlot","year":"2016","journal-title":"Br J Hosp Med (Lond)"},{"issue":"6","key":"pone.0330509.ref035","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/nep.12226","article-title":"Omeprazole-induced acute interstitial nephritis: a possible Th1-Th17-mediated injury?","volume":"19","author":"L Berney-Meyer","year":"2014","journal-title":"Nephrology (Carlton)"},{"key":"pone.0330509.ref036","doi-asserted-by":"crossref","first-page":"101464","DOI":"10.1016\/j.redox.2020.101464","article-title":"Molecular pathways driving omeprazole nephrotoxicity","volume":"32","author":"M Fontecha-Barriuso","year":"2020","journal-title":"Redox Biol"},{"issue":"1","key":"pone.0330509.ref037","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1186\/s12882-017-0688-1","article-title":"Renal association clinical practice guideline on Anaemia of Chronic Kidney Disease","volume":"18","author":"A Mikhail","year":"2017","journal-title":"BMC Nephrol"},{"issue":"12","key":"pone.0330509.ref038","first-page":"2172","article-title":"Short- and long-term omeprazole for the treatment and prevention of duodenal ulcer, and effect on Helicobacter pylori","volume":"90","author":"L Marzio","year":"1995","journal-title":"Am J Gastroenterol"},{"issue":"5","key":"pone.0330509.ref039","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ajg.2012.4","article-title":"Proton pump inhibitor therapy use does not predispose to small intestinal bacterial overgrowth","volume":"107","author":"SK Ratuapli","year":"2012","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"pone.0330509.ref040","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.cgh.2009.12.022","article-title":"Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy","volume":"8","author":"L Lombardo","year":"2010","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"1","key":"pone.0330509.ref041","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11938-004-0022-4","article-title":"Small bowel bacterial overgrowth: presentation, diagnosis, and treatment","volume":"7","author":"VV Singh","year":"2004","journal-title":"Curr Treat Options Gastroenterol"},{"issue":"10","key":"pone.0330509.ref042","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1007\/BF02093608","article-title":"Omeprazole produces parietal cell hypertrophy and hyperplasia in humans","volume":"41","author":"DK Driman","year":"1996","journal-title":"Dig Dis Sci"},{"key":"pone.0330509.ref043","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3109\/00365528909091260","article-title":"Qualitative studies of gastric endocrine cells in patients treated long-term with omeprazole","volume":"166","author":"E Solcia","year":"1989","journal-title":"Scand J Gastroenterol Suppl"},{"issue":"11","key":"pone.0330509.ref044","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1111\/jgs.12534","article-title":"Risk of proton pump inhibitor-induced mild hyponatremia in older adults","volume":"61","author":"M Buon","year":"2013","journal-title":"J Am Geriatr Soc"},{"issue":"7","key":"pone.0330509.ref045","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.3109\/0886022X.2015.1057800","article-title":"Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies","volume":"37","author":"W Cheungpasitporn","year":"2015","journal-title":"Ren Fail"},{"issue":"4","key":"pone.0330509.ref046","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1136\/dtb.2021.235385rep","article-title":"Republished: omeprazole-induced hypomagnesaemia, causing renal tubular acidosis with hypokalaemia, hypocalcaemia, hyperlactacidaemia and hyperammonaemia","volume":"59","author":"N Isse","year":"2021","journal-title":"Drug Ther Bull"},{"issue":"2","key":"pone.0330509.ref047","doi-asserted-by":"crossref","first-page":"152","DOI":"10.5527\/wjn.v5.i2.152","article-title":"Proton-pump inhibitor-induced hypomagnesemia: current research and proposed mechanisms","volume":"5","author":"JH William","year":"2016","journal-title":"World J Nephrol"},{"issue":"2","key":"pone.0330509.ref048","doi-asserted-by":"crossref","first-page":"65","DOI":"10.5414\/CNP68065","article-title":"Proton pump inhibitors and the kidney: critical review","volume":"68","author":"UC Brewster","year":"2007","journal-title":"Clin Nephrol"},{"issue":"1","key":"pone.0330509.ref049","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF01352010","article-title":"Effect of omeprazole, an inhibitor of H+,K(+)-ATPase, on bone resorption in humans","volume":"53","author":"K Mizunashi","year":"1993","journal-title":"Calcif Tissue Int"},{"issue":"1","key":"pone.0330509.ref050","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1186\/s12877-020-01794-3","article-title":"Comparing proton pump inhibitors with histamin-2 receptor blockers regarding the risk of osteoporotic fractures: a nested case-control study of more than 350,000 Korean patients with GERD and peptic ulcer disease","volume":"20","author":"JH Park","year":"2020","journal-title":"BMC Geriatr"},{"issue":"6","key":"pone.0330509.ref051","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1007\/s00223-021-00882-9","article-title":"Proton pump inhibitors inhibit PHOSPHO1 activity and matrix mineralisation in vitro","volume":"109","author":"KA Staines","year":"2021","journal-title":"Calcif Tissue Int"},{"issue":"1","key":"pone.0330509.ref052","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00198-015-3365-x","article-title":"Proton-pump inhibitors and risk of fractures: an update meta-analysis","volume":"27","author":"B Zhou","year":"2016","journal-title":"Osteoporos Int"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330509","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T17:37:38Z","timestamp":1755711458000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330509"}},"subtitle":[],"editor":[{"given":"Satish","family":"Rojekar","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":52,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0330509","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2025,8,20]]}}}