{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:08:37Z","timestamp":1792681717094,"version":"4.5.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"1206","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Opioid-induced constipation (OIC), a prevalent form of opioid-induced bowel dysfunction, significantly affects patients with chronic pain, both with and without cancer, who rely on opioid analgesics. OIC reduces opioid effectiveness, impairs quality of life and is frequently underdiagnosed and inadequately managed. A comprehensive literature search of MEDLINE and EMBASE (2000\u2013April 2025) was conducted using terms such as opioid-induced constipation, epidemiology, pathophysiology, treatment, and guidelines. Relevant studies, meta-analyses, and consensus statements were analysed to synthesize mechanistic insights and practical recommendations. This review clarifies OIC\u2019s pathophysiology, clinical evaluation, and evidence-based management strategies to guide practicing clinicians. OIC arises from opioids binding to mu-opioid receptors in the gastrointestinal tract, leading to slowed intestinal motility, reduced mucosal secretions, and increased sphincter tone, which collectively cause constipation and related symptoms. Clinicians should proactively educate patients about OIC risks at the start of opioid therapy or during dose escalation. Initial management includes prescribing over-the-counter laxatives, such as stimulant or osmotic agents, tailored to patient needs and tolerances. Regular follow-up, utilizing validated tools like the Bowel Function Index, is crucial to monitor symptom severity and adjust therapies as needed. If initial treatments fail, peripherally acting mu-opioid receptor antagonists are effective second-line options, yet they remain underutilized due to access barriers and low clinician awareness. Unlike prior reviews that primarily address pharmacologic mechanisms, this review integrates mechanistic insights with pragmatic clinical guidance, emphasizing evidence-based implementation strategies and global prescribing disparities to enhance real-world management of OIC.<\/jats:p>","DOI":"10.1093\/postmj\/qgaf211","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T13:29:53Z","timestamp":1763731793000},"page":"367-377","source":"Crossref","is-referenced-by-count":8,"title":["Opioid induced constipation: mechanisms and management"],"prefix":"10.1093","volume":"102","author":[{"given":"Erica","family":"Becker","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine , St. Louis, MO ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Y","family":"Madi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine , St. Louis, MO ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Magee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine , St. Louis, MO ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-6468","authenticated-orcid":false,"given":"Nida","family":"Ansari","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine , St. Louis, MO ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6248-7203","authenticated-orcid":false,"given":"James K","family":"Ruffle","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, University College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing-Kin","family":"Syn","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine , St. Louis, MO ,","place":["United States"]},{"name":"Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV\/EHU , Vizcaya ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asbj\u00f8rn M","family":"Drewes","sequence":"additional","affiliation":[{"name":"Mech-Sense & Center for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Clinical Institute, Aalborg University Hospital , Aalborg ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D","family":"Farmer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine , St. Louis, MO ,","place":["United States"]},{"name":"Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"2026031710060789300_ref1","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1111\/add.16081","article-title":"The opioid epidemic: a worldwide exploratory study using the WHO pharmacovigilance database","volume":"118","author":"Robert","year":"2023","journal-title":"Addiction"},{"key":"2026031710060789300_ref2","doi-asserted-by":"publisher","first-page":"15.2","DOI":"10.1136\/dtb.2018.2.0583","article-title":"Adverse effects of opioids for non-cancer pain","volume":"56","year":"2018","journal-title":"Drug Ther Bull"},{"key":"2026031710060789300_ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.rr7103a1","article-title":"CDC clinical practice guideline for prescribing opioids for pain \u2014 United States, 2022","volume":"71","author":"Dowell","year":"2022","journal-title":"MMWR Recomm Rep"},{"key":"2026031710060789300_ref4","article-title":"Opioids aware","author":"Medicine FoP","year":"2022","journal-title":"Secondary Opioids Aware"},{"key":"2026031710060789300_ref5","doi-asserted-by":"publisher","first-page":"e18","DOI":"10.5210\/ojphi.v11i2.10113","article-title":"U.S. opioid epidemic: impact on public health and review of prescription drug monitoring programs (PDMPs)","volume":"11","author":"Bote","year":"2019","journal-title":"Online J Public Health Inform"},{"key":"2026031710060789300_ref6","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1056\/NEJMp1714529","article-title":"The public and the opioid-abuse epidemic","volume":"378","author":"Blendon","year":"2018","journal-title":"N Engl J Med"},{"key":"2026031710060789300_ref7","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1056\/NEJMp1612578","article-title":"Ending the opioid epidemic - a call to action","volume":"375","author":"Murthy","year":"2016","journal-title":"N Engl J Med"},{"key":"2026031710060789300_ref8","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1200\/OP.22.00766","article-title":"Safe prescribing practices: clinicians' views on prescribing opioids to patients with early-stage cancer","volume":"19","author":"Wood","year":"2023","journal-title":"JCO Oncol Pract"},{"key":"2026031710060789300_ref9","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.amjmed.2012.11.011","article-title":"Opioids for chronic pain: new evidence, new strategies, safe prescribing","volume":"126","author":"de Leon-Casasola","year":"2013","journal-title":"Am J Med"},{"key":"2026031710060789300_ref10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/ejp.970","article-title":"European pain federation position paper on appropriate opioid use in chronic pain management","volume":"21","author":"O'Brien","year":"2017","journal-title":"Eur J Pain"},{"key":"2026031710060789300_ref11","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3399\/bjgp18X699365","article-title":"Corrections","volume":"68","year":"2018","journal-title":"Br J Gen Pract"},{"key":"2026031710060789300_ref12","doi-asserted-by":"publisher","first-page":"e13367","DOI":"10.1111\/nmo.13367","article-title":"Reduction in pain: is it worth the gain? The effect of opioids on the GI tract","volume":"30","author":"Nee","year":"2018","journal-title":"Neurogastroenterol Motil"},{"key":"2026031710060789300_ref13","doi-asserted-by":"publisher","first-page":"4083","DOI":"10.1007\/s00520-019-04688-2","article-title":"Opioid-induced bowel dysfunction: suggestions from a multidisciplinary expert board","volume":"27","author":"Rossi","year":"2019","journal-title":"Support Care Cancer"},{"key":"2026031710060789300_ref14","doi-asserted-by":"publisher","first-page":"325","DOI":"10.5055\/jom.2015.0282","article-title":"Impact of constipation on opioid therapy management among long-term opioid users, based on a patient survey","volume":"11","author":"Gupta","year":"2015","journal-title":"J Opioid Manag"},{"key":"2026031710060789300_ref15","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.sjpain.2015.12.005","article-title":"Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction-recommendations of the Nordic working group","volume":"11","author":"Drewes","year":"2016","journal-title":"Scand J Pain"},{"key":"2026031710060789300_ref16","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1007\/s11894-013-0344-2","article-title":"Opioid-induced bowel dysfunction","volume":"15","author":"Ketwaroo","year":"2013","journal-title":"Curr Gastroenterol Rep"},{"key":"2026031710060789300_ref17","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1177\/1049909106289068","article-title":"The adverse effects of morphine: a prospective survey of common symptoms during repeated dosing for chronic cancer pain","volume":"23","author":"Glare","year":"2006","journal-title":"Am J Hosp Palliat Care"},{"key":"2026031710060789300_ref18","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1111\/j.1365-2982.2009.01458.x","article-title":"Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain","volume":"22","author":"Tuteja","year":"2010","journal-title":"Neurogastroenterol Motil"},{"key":"2026031710060789300_ref19","doi-asserted-by":"publisher","first-page":"10","DOI":"10.7573\/dic.2021-7-2","article-title":"Impact of opioid-induced constipation on opioid substitution therapy management: the patient perspective","volume":"10","author":"Lugoboni","year":"2021","journal-title":"Drugs Context"},{"key":"2026031710060789300_ref20","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.2165\/11634970-000000000-00000","article-title":"Opioid-induced bowel dysfunction: pathophysiology and management","volume":"72","author":"Brock","year":"2012","journal-title":"Drugs"},{"key":"2026031710060789300_ref21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/5165682","article-title":"Prevalence and risk factors for opioid-induced constipation in an older National Veteran Cohort","volume":"2020","author":"FitzHenry","year":"2020","journal-title":"Pain Res Manag"},{"key":"2026031710060789300_ref22","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1177\/2050640616659967","article-title":"Prevalence and clinical features of opioid-induced constipation in the general population: a French study of 15,000 individuals","volume":"5","author":"Ducrotte","year":"2017","journal-title":"United European Gastroenterol J"},{"key":"2026031710060789300_ref23","doi-asserted-by":"publisher","first-page":"5831","DOI":"10.1007\/s00520-022-07002-9","article-title":"Risk factors for opioid-induced constipation in cancer patients: a single-institution, retrospective analysis","volume":"30","author":"Kanbayashi","year":"2022","journal-title":"Support Care Cancer"},{"key":"2026031710060789300_ref24","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1007\/s00520-019-04996-7","article-title":"More opioids, more constipation? Evaluation of longitudinal total oral opioid consumption and self-reported constipation in patients with cancer","volume":"28","author":"Roeland","year":"2020","journal-title":"Support Care Cancer"},{"key":"2026031710060789300_ref25","doi-asserted-by":"publisher","first-page":"236","DOI":"10.18553\/jmcp.2016.22.3.236","article-title":"The burden of opioid-induced constipation: discordance between patient and health care provider reports","volume":"22","author":"LoCasale","year":"2016","journal-title":"J Manag Care Spec Pharm"},{"key":"2026031710060789300_ref26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1526-4637.2008.00495.x","article-title":"The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European patient survey (PROBE 1)","volume":"10","author":"Bell","year":"2009","journal-title":"Pain Med"},{"key":"2026031710060789300_ref27","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1097\/AJP.0000000000000852","article-title":"Opioid-induced constipation: a review of health-related quality of life, patient burden, practical clinical considerations, and the impact of peripherally acting mu-opioid receptor antagonists","volume":"36","author":"Argoff","year":"2020","journal-title":"Clin J Pain"},{"key":"2026031710060789300_ref28","doi-asserted-by":"publisher","first-page":"S16","DOI":"10.1111\/pme.12911","article-title":"Opioid-induced constipation","volume":"16","author":"Webster","year":"2015","journal-title":"Pain Med"},{"key":"2026031710060789300_ref29","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.neulet.2003.12.004","article-title":"Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans","volume":"361","author":"Holzer","year":"2004","journal-title":"Neurosci Lett"},{"key":"2026031710060789300_ref30","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/ajgsup.2014.4","article-title":"Pharmacology of opioids and their effects on gastrointestinal function","volume":"2","author":"Holzer","year":"2014","journal-title":"Am J Gastroenterol Suppl"},{"key":"2026031710060789300_ref31","doi-asserted-by":"publisher","first-page":"3061","DOI":"10.1007\/s12035-021-02286-0","article-title":"\u03bc-Opioid receptor-mediated enteric glial activation is involved in morphine-induced constipation","volume":"58","author":"Gao","year":"2021","journal-title":"Mol Neurobiol"},{"key":"2026031710060789300_ref32","doi-asserted-by":"publisher","first-page":"1424936","DOI":"10.3389\/fnins.2024.1424936","article-title":"Novel insights into the mechanisms of loperamide-induced inhibition of colonic motility","volume":"18","author":"Parkar","year":"2024","journal-title":"Front Neurosci"},{"key":"2026031710060789300_ref33","doi-asserted-by":"publisher","first-page":"e110230","DOI":"10.1371\/journal.pone.0110230","article-title":"Opioid-induced mitogen-activated protein kinase signaling in rat enteric neurons following chronic morphine treatment","volume":"9","author":"Duraffourd","year":"2014","journal-title":"PLoS One"},{"key":"2026031710060789300_ref34","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/ajgsup.2014.5","article-title":"Molecular physiology of enteric opioid receptors","volume":"2","author":"Galligan","year":"2014","journal-title":"Am J Gastroenterol Suppl"},{"key":"2026031710060789300_ref35","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/164_2016_116","article-title":"Insights into the role of opioid receptors in the GI tract: experimental evidence and therapeutic relevance","volume":"239","author":"Galligan","year":"2017","journal-title":"Handb Exp Pharmacol"},{"key":"2026031710060789300_ref36","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1016\/j.cgh.2017.05.014","article-title":"Opioids in gastroenterology: treating adverse effects and creating therapeutic benefits","volume":"15","author":"Camilleri","year":"2017","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2026031710060789300_ref37","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.regpep.2009.03.012","article-title":"Opioid receptors in the gastrointestinal tract","volume":"155","author":"Holzer","year":"2009","journal-title":"Regul Pept"},{"key":"2026031710060789300_ref38","doi-asserted-by":"publisher","first-page":"125","DOI":"10.5114\/wo.2012.28792","article-title":"The impact of opioid analgesics on the gastrointestinal tract function and the current management possibilities","volume":"16","author":"Leppert","year":"2012","journal-title":"Contemp Oncol (Pozn)"},{"key":"2026031710060789300_ref39","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1177\/1756283X15578608","article-title":"Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities","volume":"8","author":"Nelson","year":"2015","journal-title":"Ther Adv Gastroenterol"},{"key":"2026031710060789300_ref40","doi-asserted-by":"publisher","first-page":"e13839","DOI":"10.1111\/nmo.13839","article-title":"Association between opioid usage and rectal dysfunction in constipation: a cross-sectional study of 2754 patients","volume":"32","author":"Vollebregt","year":"2020","journal-title":"Neurogastroenterol Motil"},{"key":"2026031710060789300_ref41","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1053\/j.seminoncol.2023.07.001","article-title":"Overcoming barriers to opioid-induced constipation management in cancer patients","volume":"50","author":"Martin","year":"2023","journal-title":"Semin Oncol"},{"key":"2026031710060789300_ref42","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1111\/apt.14349","article-title":"The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference","volume":"46","author":"Yiannakou","year":"2017","journal-title":"Aliment Pharmacol Ther"},{"key":"2026031710060789300_ref43","doi-asserted-by":"publisher","first-page":"e54","DOI":"10.1111\/j.1365-2982.2009.01408.x","article-title":"Psychometric performance and clinical meaningfulness of the patient assessment of constipation-quality of life questionnaire in prucalopride (RESOLOR) trials for chronic constipation","volume":"22","author":"Dubois","year":"2010","journal-title":"Neurogastroenterol Motil"},{"key":"2026031710060789300_ref44","doi-asserted-by":"publisher","first-page":"920","DOI":"10.3109\/00365529709011203","article-title":"Stool form scale as a useful guide to intestinal transit time","volume":"32","author":"Lewis","year":"1997","journal-title":"Scand J Gastroenterol"},{"key":"2026031710060789300_ref45","doi-asserted-by":"publisher","first-page":"371","DOI":"10.3111\/13696990903430481","article-title":"Validation of the bowel function index to detect clinically meaningful changes in opioid-induced constipation","volume":"12","author":"Rentz","year":"2009","journal-title":"J Med Econ"},{"key":"2026031710060789300_ref46","doi-asserted-by":"publisher","first-page":"131","DOI":"10.5056\/jnm23144","article-title":"Opioid-induced constipation: old and new concepts in diagnosis and treatment","volume":"30","author":"Squeo","year":"2024","journal-title":"J Neurogastroenterol Motil"},{"key":"2026031710060789300_ref47","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1093\/jnci\/djad068","article-title":"Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer","volume":"115","author":"Fritz","year":"2023","journal-title":"J Natl Cancer Inst"},{"key":"2026031710060789300_ref48","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00520-012-1494-8","article-title":"Laxative prescriptions to cancer outpatients receiving opioids: a study from the Norwegian prescription database","volume":"21","author":"Skollerud","year":"2013","journal-title":"Support Care Cancer"},{"key":"2026031710060789300_ref49","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1053\/j.gastro.2017.01.031","article-title":"The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association","volume":"152","author":"Freedberg","year":"2017","journal-title":"Gastroenterology"},{"key":"2026031710060789300_ref50","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1111\/papr.12515","article-title":"Tapentadol prolonged release for chronic pain: a review of clinical trials and 5 years of routine clinical practice data","volume":"17","author":"Baron","year":"2017","journal-title":"Pain Pract"},{"key":"2026031710060789300_ref51","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1089\/jpm.2007.0200","article-title":"Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature","volume":"11","author":"Tassinari","year":"2008","journal-title":"J Palliat Med"},{"key":"2026031710060789300_ref52","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1177\/2049463720945289","article-title":"To what extent are we confident that tapentadol induces less constipation and other side effects than the other opioids in chronic pain patients? A confidence evaluation in network meta-analysis","volume":"15","author":"Forget","year":"2021","journal-title":"Br J Pain"},{"key":"2026031710060789300_ref53","doi-asserted-by":"publisher","first-page":"e14131","DOI":"10.1111\/nmo.14131","article-title":"Tapentadol results in less deterioration of gastrointestinal function and symptoms than standard opioid therapy in healthy male volunteers","volume":"33","author":"Mark","year":"2021","journal-title":"Neurogastroenterol Motil"},{"key":"2026031710060789300_ref54","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.bpg.2010.02.008","article-title":"Adverse effects of drugs on small intestine and colon","volume":"24","author":"Zeino","year":"2010","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"2026031710060789300_ref55","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1093\/pm\/pnw240","article-title":"Laxatives do not improve symptoms of opioid-induced constipation: results of a patient survey","volume":"18","author":"Emmanuel","year":"2017","journal-title":"Pain Med"},{"key":"2026031710060789300_ref56","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1046\/j.1365-2982.2003.00426.x","article-title":"Abdominal distension after colonic lactulose fermentation recorded by a new extensometer","volume":"15","author":"Basilisco","year":"2003","journal-title":"Neurogastroenterol Motil"},{"key":"2026031710060789300_ref57","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.2147\/JPR.S243435","article-title":"Naldemedine: a new option for OIBD","volume":"13","author":"Coluzzi","year":"2020","journal-title":"J Pain Res"},{"key":"2026031710060789300_ref58","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1053\/j.gastro.2018.07.016","article-title":"American Gastroenterological Association Institute guideline on the medical management of opioid-induced constipation","volume":"156","author":"Crockett","year":"2019","journal-title":"Gastroenterology"},{"key":"2026031710060789300_ref59","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1080\/17474124.2023.2267441","article-title":"Recommendations for the management of opioid-induced constipation - how to improve usability in clinical practice","volume":"17","author":"Okdahl","year":"2023","journal-title":"Expert Review of Gastroenterology & Hepatology"},{"key":"2026031710060789300_ref60","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s40265-014-0177-9","article-title":"Oxycodone\/naloxone prolonged-release: a review of its use in the management of chronic pain while counteracting opioid-induced constipation","volume":"74","author":"Burness","year":"2014","journal-title":"Drugs"},{"key":"2026031710060789300_ref61","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1016\/j.jpain.2008.06.014","article-title":"Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain","volume":"9","author":"Vondrackova","year":"2008","journal-title":"J Pain"},{"key":"2026031710060789300_ref62","doi-asserted-by":"publisher","first-page":"3503","DOI":"10.1185\/03007990802584454","article-title":"Fixed-ratio combination oxycodone\/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain","volume":"24","author":"Simpson","year":"2008","journal-title":"Curr Med Res Opin"},{"key":"2026031710060789300_ref63","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1517\/14656560902796798","article-title":"Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomised controlled trial","volume":"10","author":"Lowenstein","year":"2009","journal-title":"Expert Opin Pharmacother"},{"key":"2026031710060789300_ref64","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1097\/j.pain.0000000000000230","article-title":"A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment","volume":"156","author":"Rauck","year":"2015","journal-title":"Pain"},{"key":"2026031710060789300_ref65","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1007\/s00520-011-1346-y","article-title":"Some concerns about the article: \"high doses of oxycodone-naloxone combination may provide poor analgesia.\"","volume":"20","author":"Compagnone","year":"2012","journal-title":"Support Care Cancer"},{"key":"2026031710060789300_ref66","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1586\/egh.09.42","article-title":"Methylnaltrexone: a novel approach for the management of opioid-induced constipation in patients with advanced illness","volume":"3","author":"Diego","year":"2009","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"2026031710060789300_ref67","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.jpain.2010.11.008","article-title":"Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic, nonmalignant pain: a randomized controlled study","volume":"12","author":"Michna","year":"2011","journal-title":"J Pain"},{"key":"2026031710060789300_ref68","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1111\/papr.12535","article-title":"Randomized, double-blind trial of oral methylnaltrexone for the treatment of opioid-induced constipation in patients with chronic noncancer pain","volume":"17","author":"Rauck","year":"2017","journal-title":"Pain Pract"},{"key":"2026031710060789300_ref69","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1056\/NEJMoa1310246","article-title":"Naloxegol for opioid-induced constipation in patients with noncancer pain","volume":"370","author":"Chey","year":"2014","journal-title":"N Engl J Med"},{"key":"2026031710060789300_ref70","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1016\/j.pain.2013.04.024","article-title":"A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation","volume":"154","author":"Webster","year":"2013","journal-title":"Pain"},{"key":"2026031710060789300_ref71","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/S2468-1253(17)30105-X","article-title":"Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials","volume":"2","author":"Hale","year":"2017","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026031710060789300_ref72","first-page":"A121","article-title":"OP284 patient-reported outcomes with naldemedine long-term treatment of opioid-induced constipation in subjects with chronic non-cancer pain","volume":"5","author":"Tack","year":"2017","journal-title":"UEG Journal"},{"key":"2026031710060789300_ref73","doi-asserted-by":"publisher","first-page":"3859","DOI":"10.1200\/JCO.2017.73.0853","article-title":"Randomized phase III and extension studies of Naldemedine in patients with opioid-induced constipation and cancer","volume":"35","author":"Katakami","year":"2017","journal-title":"J Clin Oncol"},{"key":"2026031710060789300_ref74","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s40266-020-00753-2","article-title":"Safety and efficacy of Naldemedine for the treatment of opioid-induced constipation in patients with chronic non-cancer pain receiving opioid therapy: a subgroup analysis of patients &gt;\/= 65 years of age","volume":"37","author":"Wild","year":"2020","journal-title":"Drugs Aging"},{"key":"2026031710060789300_ref75","doi-asserted-by":"publisher","first-page":"C1173","DOI":"10.1152\/ajpcell.00528.2003","article-title":"SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents","volume":"287","author":"Cuppoletti","year":"2004","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026031710060789300_ref76","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1517\/17425255.2013.876410","article-title":"Lubiprostone: pharmacokinetic, pharmacodynamic, safety and regulatory aspects in the treatment of constipation-predominant irritable bowel syndrome","volume":"10","author":"Raschi","year":"2014","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2026031710060789300_ref77","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1111\/pme.12437","article-title":"A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain","volume":"15","author":"Cryer","year":"2014","journal-title":"Pain Med"},{"key":"2026031710060789300_ref78","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/ajg.2015.106","article-title":"A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain","volume":"110","author":"Jamal","year":"2015","journal-title":"Am J Gastroenterol"},{"key":"2026031710060789300_ref79","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/papr.12444","article-title":"Lubiprostone for opioid-induced constipation does not interfere with opioid analgesia in patients with chronic noncancer pain","volume":"17","author":"Spierings","year":"2017","journal-title":"Pain Pract"},{"key":"2026031710060789300_ref80","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1517\/17425255.2011.572875","article-title":"The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide","volume":"7","author":"Lee","year":"2011","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2026031710060789300_ref81","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1097\/j.pain.0000000000001754","article-title":"Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study","volume":"161","author":"Brenner","year":"2020","journal-title":"Pain"},{"key":"2026031710060789300_ref82","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1007\/s10620-010-1229-y","article-title":"Efficacy and safety of prucalopride in patients with chronic noncancer pain suffering from opioid-induced constipation","volume":"55","author":"Sloots","year":"2010","journal-title":"Dig Dis Sci"},{"key":"2026031710060789300_ref83","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1177\/2050640618818305","article-title":"Pathophysiology and management of opioid-induced constipation: European expert consensus statement","volume":"7","author":"Farmer","year":"2019","journal-title":"United European Gastroenterol J"},{"key":"2026031710060789300_ref84","doi-asserted-by":"publisher","first-page":"3589","DOI":"10.1007\/s12325-021-01766-y","article-title":"Management of Opioid-Induced Constipation and Bowel Dysfunction: expert opinion of an Italian multidisciplinary panel","volume":"38","author":"De Giorgio","year":"2021","journal-title":"Adv Ther"},{"key":"2026031710060789300_ref85","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1188\/20.ONF.671-691","article-title":"ONS guidelines for opioid-induced and non-opioid-related cancer constipation","volume":"47","author":"Rogers","year":"2020","journal-title":"Oncol Nurs Forum"},{"key":"2026031710060789300_ref86","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1748-5908-6-26","article-title":"How can we improve guideline use? A conceptual framework of implementability","volume":"6","author":"Gagliardi","year":"2011","journal-title":"Implement Sci"},{"key":"2026031710060789300_ref87","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.dld.2005.06.011","article-title":"The general practitioner's approach to irritable bowel syndrome: from intention to practice","volume":"37","author":"Bellini","year":"2005","journal-title":"Dig Liver Dis"},{"key":"2026031710060789300_ref88","first-page":"15","article-title":"Characteristics of effective clinical guidelines for general practice","volume":"53","author":"Burgers","year":"2003","journal-title":"Br J Gen Pract"},{"key":"2026031710060789300_ref89","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1089\/jpm.2021.0438","article-title":"Japanese Society of Palliative Medicine. Revision of pharmacological treatment recommendations for cancer pain: clinical guidelines from the Japanese Society of Palliative Medicine","volume":"25","author":"Mawatari","year":"2022","journal-title":"J Palliat Med"},{"key":"2026031710060789300_ref90","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1007\/s40122-023-00520-2","article-title":"A Nationwide Hospital claims database analysis of real-world patterns of laxative use for opioid-induced constipation in Japanese patients with cancer","volume":"12","author":"Higashibata","year":"2023","journal-title":"Pain Ther"}],"container-title":["Postgraduate Medical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pmj\/article-pdf\/102\/1206\/367\/65885041\/qgaf211.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pmj\/article-pdf\/102\/1206\/367\/65885041\/qgaf211.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:06:15Z","timestamp":1773756375000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pmj\/article\/102\/1206\/367\/8380237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,15]]},"references-count":90,"journal-issue":{"issue":"1206","published-online":{"date-parts":[[2025,12,15]]},"published-print":{"date-parts":[[2026,3,17]]}},"URL":"https:\/\/doi.org\/10.1093\/postmj\/qgaf211","relation":{},"ISSN":["0032-5473","1469-0756"],"issn-type":[{"value":"0032-5473","type":"print"},{"value":"1469-0756","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2025,12,15]]}}}