{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:50:28Z","timestamp":1785469828058,"version":"3.56.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"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 gastrointestinal obstruction (DIGO) and gastrointestinal perforation (DIGP) may be the result of gastrointestinal hypomotility and severe constipation, which may lead to potentially fatal complications of bowel ischemia, sepsis and perforation. We evaluated the onset profile of DIGs (DIGO and DIGP) associated with prescription drugs by analyzing data in the Japanese Adverse Drug Event Report (JADER) database. We selected 161 DIG-related drugs and categorized them into 19 classes based on the Anatomical Therapeutic Chemical (ATC) Classification System. Finally, we focused on 58 drugs and conducted subsequent analyses for the time-to-onset and outcomes. We extracted 79 preferred terms (PTs) with the strings \u201cileus,\u201d \u201cstenosis,\u201d \u201cobstruction,\u201d \u201cobstructive,\u201d \u201cimpaction,\u201d \u201cperforation,\u201d \u201cperforated,\u201d \u201chypomotility,\u201d and \u201cintussusception\u201d from the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) of SMQ20000104: gastrointestinal perforation, ulcer, hemorrhage, obstruction non-specific findings\/procedures; SMQ20000105: gastrointestinal obstruction; and SMQ20000107: gastrointestinal perforation. Among the 667, 729 reports in the JADER database submitted between April 2004 and November 2020, we identified 11,351 occurrences of DIGs. The reporting odds ratios (RORs) (95% confidence interval) of \u201cbarium sulfate containing X-ray media,\u201d \u201cdrugs for treatment of hyperkalemia and hyperphosphatemia,\u201d and \u201coral bowel cleanser\u201d were 142.0 (127.1\u2013158.6), 25.8 (23.1\u201328.8), and 29.7 (24.8\u201335.6), respectively. The median number of days (interquartile range) until the onset of an adverse event caused by each drug category was as follows: barium sulfate containing X-ray contrast media [2.0 (1.0\u20133.0)], diazepines, oxazepines, thiazepines, and oxepines [8.0 (8.0\u201318.5)], drugs for treatment of hyperkalemia and hyperphosphatemia [29.0 (8.0\u201355.0)], non-selective monoamine reuptake inhibitors [19.0 (7.0\u201347.5)], and oral bowel cleanser [0.0 (0.0\u20130.0)]. Depending on the drug, the time to onset of side effects ranged from days to several months. Our results highlighted the need to perform detailed monitoring of each drug for possible association with DIGs, which might otherwise have fatal consequences.<\/jats:p>","DOI":"10.3389\/fphar.2021.692292","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T10:24:43Z","timestamp":1627295083000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Analysis of Drug-Induced Gastrointestinal Obstruction and Perforation Using the Japanese Adverse Drug Event Report Database"],"prefix":"10.3389","volume":"12","author":[{"given":"Riko","family":"Satake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoka","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ririka","family":"Mukai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyo","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Iguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Ikesue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Nishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Hashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"B1","article-title":"Intestinal Perforation and Intestinal Obstruction Caused by Oral Intestinal Cleansing Agent (Nifrec), No. 03-01","volume-title":"Dear Healthcare Professional Letters of Emergent Safety Communications","author":"Ajinomoto Pharma Co, Ltd","year":"2003"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0163583","DOI":"10.1371\/journal.pone.0163583","article-title":"Assessment of the Risk of Suicide-Related Events Induced by Concomitant Use of Antidepressants in Cases of Smoking Cessation Treatment with Varenicline and Assessment of Latent Risk by the Use of Varenicline","volume":"11","author":"Akimoto","year":"2016","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1053\/j.gastro.2017.10.04910.1053\/j.gastro.2017.10.049","article-title":"Mechanisms of Damage to the Gastrointestinal Tract from Nonsteroidal Anti-inflammatory Drugs","volume":"154","author":"Bjarnason","year":"2018","journal-title":"Gastroenterology"},{"key":"B4","unstructured":"Sevelamer Hydrochloride Safety Information Lenagel Tablets 250 Mg\/Fosblock Tablets 250 Mg\n            Chugai Pharmaceutical, Co., Ltd\n          2003"},{"key":"B5","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1177\/2042098618756261","article-title":"Safety of Antipsychotics for the Treatment of Schizophrenia: a Focus on the Adverse Effects of Clozapine","volume":"9","author":"De Berardis","year":"2018","journal-title":"Ther. Adv. Drug Saf."},{"key":"B6","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1046\/j.1365-2125.2002.01569.x","article-title":"Non-sedating Antihistamine Drugs and Cardiac Arrhythmias - Biased Risk Estimates from Spontaneous Reporting Systems?","volume":"53","author":"De Bruin","year":"2002","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B7","unstructured":"HIGHLIGHTS of PRESCRIBING INFORMATION: RYANODEX\u00ae (Dantrolene Sodium) for Injectable Suspension, for Intravenous Use2017"},{"key":"B8","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s40263-017-0448-6","article-title":"Clozapine-Induced Gastrointestinal Hypomotility: A 22-Year Bi-national Pharmacovigilance Study of Serious or Fatal 'Slow Gut' Reactions, and Comparison with International Drug Safety Advice","volume":"31","author":"Every-Palmer","year":"2017","journal-title":"CNS Drugs"},{"key":"B9","doi-asserted-by":"publisher","first-page":"CD011128","DOI":"10.1002\/14651858.CD011128.pub2","article-title":"Pharmacological Treatment for Antipsychotic-Related Constipation","volume":"1","author":"Every-Palmer","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"B10","unstructured":"HIGHLIGHTS of PRESCRIBING INFORMATION: E-Z-CAT DRY (Barium Sulfate) for Oral Suspension2017"},{"key":"B11","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1136\/bmj.3.5977.207","article-title":"Vincristine-induced Autonomic Neuropathy","volume":"3","author":"Hancock","year":"1975","journal-title":"Bmj"},{"key":"B12","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.amjmed.2012.08.0110.1016\/j.amjmed.2012.08.016","article-title":"Gastrointestinal Adverse Events with Sodium Polystyrene Sulfonate (Kayexalate) Use: a Systematic Review","volume":"126","author":"Harel","year":"2013","journal-title":"Am. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1592\/phco.24.8.743.36068","article-title":"Replication of the Weber Effect Using Postmarketing Adverse Event Reports Voluntarily Submitted to the United States Food and Drug Administration","volume":"24","author":"Hartnell","year":"2004","journal-title":"Pharmacotherapy"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1002\/pds.5108","article-title":"Analysis of Immune\u2010related Adverse Events Caused by Immune Checkpoint Inhibitors Using the Japanese Adverse Drug Event Report Database","volume":"29","author":"Hasegawa","year":"2020","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B15","doi-asserted-by":"publisher","first-page":"607","DOI":"10.3143\/geriatrics.33.607","article-title":"Occurrence of Ileus after Voglibose Treatment in an Elderly Diabetic Patient with Gait Disturbance Caused by Cerebral Hemorrhage","volume":"33","author":"Hayaishi","year":"1996","journal-title":"Jpn. J. Geriat"},{"key":"B16","doi-asserted-by":"publisher","first-page":"7329","DOI":"10.1073\/pnas.1510502113","article-title":"Characterizing Treatment Pathways at Scale Using the OHDSI Network","volume":"113","author":"Hripcsak","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B17","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.bpg.2009.02.012","article-title":"Intestinal and Anorectal Motility and Functional Disorders","volume":"23","author":"Keller","year":"2009","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1002\/pds.1633","article-title":"Identifying Patterns of Adverse Event Reporting for Four Members of the Angiotensin II Receptor Blockers Class of Drugs: Revisiting the Weber Effect","volume":"17","author":"McAdams","year":"2008","journal-title":"Pharmacoepidem. Drug Safe."},{"key":"B19","unstructured":"Introductory Guide for Standardized MedDRA Queries (SMQs) Version 23.1\n            MedDRA, Msso\n          2020"},{"key":"B20","unstructured":"Jutoku Fukusayo Shikkanbetsu Taiou Manual: Mahisei Ireusu (The Manual for Handling Disorders Due to Adverse Drug Reactions: Paralytic Ileus)2008"},{"key":"B21","unstructured":"Pharmaceutical and Food Safety Bureau. Pharmaceuticals and Medical Devices Safety Information No. 2192005"},{"key":"B22","doi-asserted-by":"publisher","first-page":"609","DOI":"10.2165\/00002018-200831070-00006","article-title":"Influence of Regulatory Measures on the Rate of Spontaneous Adverse Drug Reaction Reporting in Italy","volume":"31","author":"Motola","year":"2008","journal-title":"Drug Saf."},{"key":"B23","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1093\/schbul\/sbq137","article-title":"Risk Factors for Ileus in Patients with Schizophrenia","volume":"38","author":"Nielsen","year":"2012","journal-title":"Schizophrenia Bull."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1001\/jamainternmed.2019.0631","article-title":"Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated with Sodium Polystyrene Sulfonate Use in Patients of Advanced Age","volume":"179","author":"Noel","year":"2019","journal-title":"JAMA Intern. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1272\/jnms.68.61","article-title":"Ileus after Administration of Cold Remedy in an Elderly Diabetic Patient Treated with Acarbose","volume":"68","author":"Oba","year":"2001","journal-title":"J. Nippon Med. Sch."},{"key":"B26","doi-asserted-by":"publisher","first-page":"891","DOI":"10.2165\/00002018-200730100-00007","article-title":"Impact of Safety Alerts on Measures of Disproportionality in Spontaneous Reporting Databases","volume":"30","author":"Pariente","year":"2007","journal-title":"Drug Saf."},{"key":"B27","first-page":"265","article-title":"Data Mining Techniques in Pharmacovigilance: Analysis of the Publicly Accessible FDA Adverse Event Reporting System (AERS)","author":"Poluzzi","year":"2012"},{"key":"B28","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":"B29","unstructured":"A Systematic Approach to Improving the Reliability and Scale of Evidence from Health Care Data\n            SchuemieM. J.\n            RyanP. B.\n            HripcsakG.\n            MadiganD.\n            SuchardM. A.\n          2018"},{"key":"B30","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1182\/asheducation-2010.1.423","article-title":"Dealing with Neuropathy in Plasma-Cell Dyscrasias","volume":"2010","author":"Sonneveld","year":"2010","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"B31","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1248\/bpb.b14-00191","article-title":"Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database","volume":"38","author":"Suzuki","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1248\/bpb.b17-00266","article-title":"Influence of Japanese Regulatory Action on Denosumab-Related Hypocalcemia Using Japanese Adverse Drug Event Report Database","volume":"40","author":"Takeyama","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1093\/ije\/dyy120","article-title":"Evaluating Large-Scale Propensity Score Performance through Real-World and Synthetic Data Experiments","volume":"47","author":"Tian","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/pds.668","article-title":"A Comparison of Measures of Disproportionality for Signal Detection in Spontaneous Reporting Systems for Adverse Drug Reactions","volume":"11","author":"van Puijenbroek","year":"2002","journal-title":"Pharmacoepidem. Drug Safe."},{"key":"B35","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1046\/j.1365-2125.1999.00957.x","article-title":"Signalling Possible Drug-Drug Interactions in a Spontaneous Reporting System: Delay of Withdrawal Bleeding during Concomitant Use of Oral Contraceptives and Itraconazole","volume":"47","author":"van Puijenbroek","year":"1999","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"508","DOI":"10.3238\/arztebl.2017.0508","article-title":"Ileus in Adults","volume":"114","author":"Vilz","year":"2017","journal-title":"Dtsch. Arztebl. Int."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1007\/s40264-019-00861-y","article-title":"Data-driven Identification of Adverse Event Reporting Patterns for Japan in VigiBase, the WHO Global Database of Individual Case Safety Reports","volume":"42","author":"Wakao","year":"2019","journal-title":"Drug Saf."},{"key":"B38","doi-asserted-by":"publisher","first-page":"233","DOI":"10.2165\/00002018-200124030-00006","article-title":"Temporal Patterns of NSAID Spontaneous Adverse Event Reports","volume":"24","author":"Wallenstein","year":"2001","journal-title":"Drug Saf."},{"key":"B39","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1002\/sim.8457","article-title":"Propensity Score\u2010adjusted Three\u2010component Mixture Model for Drug\u2010drug Interaction Data Mining in FDA Adverse Event Reporting System","volume":"39","author":"Wang","year":"2020","journal-title":"Stat. Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.692292\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T10:24:49Z","timestamp":1627295089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.692292\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,26]]},"references-count":39,"alternative-id":["10.3389\/fphar.2021.692292"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.692292","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,26]]},"article-number":"692292"}}