{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:04:51Z","timestamp":1793228691306,"version":"4.5.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"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:p>This study comprehensively evaluated the safety profile of Vonoprazan using data from the FDA Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2023 through the first quarter (Q1) of 2025. This analysis was restricted to real-world reports collected after the U. S. approval of vonoprazan, to better reflect its current clinical use pattern in the United States. Reports in which Vonoprazan was designated as the primary suspect(PS) drug were systematically extracted, and duplicate entries were removed using MySQL(version 8.0.42). Adverse events were coded in according tothe Medical Dictionary for Regulatory Activities (MedDRA, version 24.0). To detect potential safety signals, four disproportionality methods were applied: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Differences between serious and non-serious adverse events were further examined using Pearson\u2019s chi-square test and Fisher\u2019s exact test. Temporal patterns of adverse event occurrence were evaluated using Time-to-Onset (TTO) analysis and Weibull Shape Parameter (WSP) modeling. In total, 978 vonoprazan-related cases were included; females accounted 62.0% of reports, and 34.3% of events were classified as serious. Forty seven preferred terms (PTs) met predefined signal criteria, and 16 of these, such as facial paralysis and cholecystitis, were not listed in the current U. S. FDA prescribing information for vonoprazan. Serious adverse events were more often associated with renal impairment and haematemesis, whereas non-serious events were predominantly gastrointestinal. Stratified analyses further revealed several potential high-risk signals, particularly inmale and elderly patients. The median time to onset was 7\u202fdays, and most events occurred within the first 30\u202fdays after treatment initiation. Weighted Survival Probability (WSP) analysis suggested an \u201cearly failure\u201d pattern, and co-administration of aspirin and other acid-suppressing agents was common. In conclusion, this study provides a systematic characterization of Vonoprazan- associated adverse events and highlights several potential new safety signals that are not currently reflected in the drug\u2019s labeling, these findings should be interpreted as hypothesis-generating safety signals that may inform future prospective monitoring and clinician counseling.<\/jats:p>","DOI":"10.3389\/fmed.2025.1688914","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T06:25:56Z","timestamp":1766125556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Vonoprazan-related adverse events: a pharmacovigilance study based on the FDA adverse event reporting system"],"prefix":"10.3389","volume":"12","author":[{"given":"Yali","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1053\/j.gastro.2022.05.055","article-title":"Vonoprazan triple and dual therapy for Helicobacter pylori infection in the United States and Europe: randomized clinical trial","volume":"163","author":"Chey","year":"2022","journal-title":"Gastroenterology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1007\/s40265-025-02193-x","article-title":"Vonoprazan: a review in erosive esophagitis and non-erosive gastro-esophageal reflux disease","volume":"85","author":"Fung","year":"2025","journal-title":"Drugs"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s40265-015-0368-z","article-title":"Vonoprazan: first global approval","volume":"75","author":"Garnock-Jones","year":"2015","journal-title":"Drugs"},{"key":"ref4","year":""},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1080\/14656566.2024.2427335","article-title":"Evaluating Vonoprazan for the treatment of erosive GERD and heartburn associated with GERD in adults","volume":"25","author":"Marabotto","year":"2024","journal-title":"Expert Opin Pharmacother"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1016\/j.cgh.2024.05.004","article-title":"Vonoprazan is efficacious for treatment of heartburn in non-erosive reflux disease: a randomized trial","volume":"22","author":"Laine","year":"2024","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1111\/apt.18458","article-title":"Integrated analysis of Vonoprazan safety for symptomatic gastro-Oesophageal reflux disease or erosive Oesophagitis","volume":"61","author":"Howden","year":"2025","journal-title":"Aliment Pharmacol Ther"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1177\/87551225231166531","article-title":"Vonoprazan: a new potassium-competitive acid blocker","volume":"39","author":"St Onge","year":"2023","journal-title":"J Pharm Technol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1002\/cpdd.1357","article-title":"Clinical study on the eradication of Helicobacter pylori by Vonoprazan combined with amoxicillin for 10-day dual therapy","volume":"13","author":"Yan","year":"2024","journal-title":"Clin Pharmacol Drug Dev"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"987","DOI":"10.21037\/atm-22-4133","article-title":"The efficacy of vonoprazan combined with different dose amoxicillin on eradication of Helicobacter pylori: an open, multicenter, randomized clinical study","volume":"10","author":"Lin","year":"2022","journal-title":"Ann Transl Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1111\/apt.13324","article-title":"Systematic review: the effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology","volume":"42","author":"Lundell","year":"2015","journal-title":"Aliment Pharmacol Ther"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"20420986241260211","DOI":"10.1177\/20420986241260211","article-title":"Vonoprazan-associated Clostridioides difficile infection: an analysis of the Japanese adverse drug event report and the FDA adverse event reporting system","volume":"15","author":"Ouyang","year":"2024","journal-title":"Ther Adv Drug Saf"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"45776","DOI":"10.1177\/1756283X17745776","article-title":"Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date","volume":"11","author":"Sugano","year":"2018","journal-title":"Ther Adv Gastroenterol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.cegh.2017.12.008","article-title":"Proton pump inhibitors use and risk of chronic kidney disease: evidence-based meta-analysis of observational studies","volume":"7","author":"Hussain","year":"2019","journal-title":"Clin Epidemiol Glob Health"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3390\/ph13100276","article-title":"The potential benefits of Vonoprazan as Helicobacter pylori infection therapy","volume":"13","author":"Miftahussurur","year":"2020","journal-title":"Pharmaceuticals (Basel)"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1124\/dmd.120.000017","article-title":"Application of Azamulin to determine the contribution of CYP3A4\/5 to drug metabolic clearance using human hepatocytes","volume":"48","author":"Chanteux","year":"2020","journal-title":"Drug Metab Dispos"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41401-019-0353-2","article-title":"Physiologically based pharmacokinetic-pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous\/oral administration to rats, dogs and humans","volume":"41","author":"Kong","year":"2020","journal-title":"Acta Pharmacol Sin"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"909168","DOI":"10.3389\/fphar.2022.909168","article-title":"Evaluation of commonly used cardiovascular drugs in inhibiting vonoprazan metabolism in vitro and in vivo","volume":"13","author":"Wang","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.2147\/DDDT.S255427","article-title":"Effects of Voriconazole on the pharmacokinetics of Vonoprazan in rats","volume":"14","author":"Shen","year":"2020","journal-title":"Drug Des Devel Ther"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"754849","DOI":"10.3389\/fphar.2021.754849","article-title":"Co-Administration of Vonoprazan, not Tegoprazan, affects the pharmacokinetics of atorvastatin in healthy male subjects","volume":"12","author":"Hwang","year":"2021","journal-title":"Front Pharmacol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1002\/jcph.2019","article-title":"A population pharmacokinetic model of Vonoprazan: evaluating the effects of race, disease status, and other covariates on exposure","volume":"62","author":"Scarpignato","year":"2022","journal-title":"J Clin Pharmacol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"7588085","DOI":"10.1155\/2023\/7588085","article-title":"Adverse reaction signals mining of Vonoprazan: a pharmacovigilance study based on FAERS","volume":"2023","author":"Chi","year":"2023","journal-title":"J Clin Pharm Ther"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1007\/s40264-025-01560-7","article-title":"An evaluation of duplicate adverse event reports characteristics in the Food and Drug Administration adverse event reporting system","volume":"48","author":"Janiczak","year":"2025","journal-title":"Drug Saf"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"862508","DOI":"10.3389\/fphar.2022.862508","article-title":"Post-marketing safety concerns with Secukinumab: a disproportionality analysis of the FDA adverse event reporting system","volume":"13","author":"Shu","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"101425","DOI":"10.1016\/j.eclinm.2022.101425","article-title":"Risk of hepatitis B virus reactivation following treatment with abatacept: a retrospective study of international pharmacovigilance databases","volume":"48","author":"Wang","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3389\/fdsfr.2023.1323057","article-title":"Conducting and interpreting disproportionality analyses derived from spontaneous reporting systems","volume":"3","author":"Cutroneo","year":"2024","journal-title":"Front Drug Saf Regul"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.3390\/ph17081028","article-title":"Adverse event profiles of adalimumab in children: a disproportionality analysis","volume":"17","author":"Zhang","year":"2024","journal-title":"Pharmaceuticals (Basel)"},{"key":"ref28","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":"ref29","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1177\/0962280211403604","article-title":"Shrinkage observed-to-expected ratios for robust and transparent large-scale pattern discovery","volume":"22","author":"Nor\u00e9n","year":"2013","journal-title":"Stat Methods Med Res"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"381","DOI":"10.2165\/00002018-200225060-00001","article-title":"Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the US FDA\u2019S spontaneous reports database","volume":"25","author":"Szarfman","year":"2002","journal-title":"Drug Saf"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"107498","DOI":"10.1016\/j.intimp.2021.107498","article-title":"Immune-related adverse events associated with immune checkpoint inhibitors: an updated comprehensive disproportionality analysis of the FDA adverse event reporting system","volume":"95","author":"Chen","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40780-016-0048-5","article-title":"Analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis using the Japanese adverse drug event report database","volume":"2","author":"Abe","year":"2016","journal-title":"J Pharm Health Care Sci"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1007\/s40264-013-0061-7","article-title":"Illustration of the weibull shape parameter signal detection tool using electronic healthcare record data","volume":"36","author":"Sauzet","year":"2013","journal-title":"Drug Saf"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/s1542-3565(05)00153-9","article-title":"Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US upper gastrointestinal study","volume":"3","author":"Camilleri","year":"2005","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1186\/s12889-018-6031-3","article-title":"Gastroesophageal reflux disease and its related factors among women of reproductive age: Korea nurses\u2019 health study","volume":"18","author":"Kim","year":"2018","journal-title":"BMC Public Health"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1186\/s12916-016-0718-z","article-title":"Effective and safe proton pump inhibitor therapy in acid-related diseases - a position paper addressing benefits and potential harms of acid suppression","volume":"14","author":"Scarpignato","year":"2016","journal-title":"BMC Med"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1111\/apt.16295","article-title":"Review article: potassium-competitive acid blockers for the treatment of acid-related disorders","volume":"53","author":"Abdel-Aziz","year":"2021","journal-title":"Aliment Pharmacol Ther"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"3308","DOI":"10.1111\/jgh.15700","article-title":"Randomized clinical trial: 7-day vonoprazan-based versus 14-day omeprazole-based triple therapy for Helicobacter pylori","volume":"36","author":"Bunchorntavakul","year":"2021","journal-title":"J Gastroenterol Hepatol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1111\/apt.17070","article-title":"Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication","volume":"56","author":"Ang","year":"2022","journal-title":"Aliment Pharmacol Ther"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1136\/gutjnl-2017-314605","article-title":"Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study","volume":"67","author":"Cheung","year":"2018","journal-title":"Gut"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3390\/ph18010114","article-title":"Post-marketing pharmacovigilance of Canakinumab from the FDA adverse event reporting system (FAERS)","volume":"18","author":"Zhang","year":"2025","journal-title":"Pharmaceuticals (Basel)"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1688914\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T06:25:58Z","timestamp":1766125558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1688914\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":41,"alternative-id":["10.3389\/fmed.2025.1688914"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1688914","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]},"article-number":"1688914"}}