{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T08:56:53Z","timestamp":1770454613703,"version":"3.49.0"},"reference-count":42,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"Elsevier Evidence-Based Medicine Center"}],"content-domain":{"domain":["amjmed.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Medicine"],"published-print":{"date-parts":[[2018,9]]},"DOI":"10.1016\/j.amjmed.2018.02.038","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T10:43:50Z","timestamp":1522665830000},"page":"1041-1051.e3","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Management of Opioid-Induced Constipation in Patients with Malignancy"],"prefix":"10.1016","volume":"131","author":[{"given":"Jose M.","family":"Garcia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3584-2008","authenticated-orcid":false,"given":"Tatyana A.","family":"Shamliyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"suppl 1","key":"10.1016\/j.amjmed.2018.02.038_bib0010","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1089\/jpm.2008.9839.supp","article-title":"Palliative care and pain: new strategies for managing opioid bowel dysfunction","volume":"11","author":"Thomas","year":"2008","journal-title":"J Palliat Med"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0015","article-title":"Constipation: opioid antagonists in people prescribed opioids","volume":"2015","author":"Ahmedzai","year":"2015","journal-title":"BMJ Clin Evid"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0020","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.jpainsymman.2010.03.026","article-title":"Consensus recommendations for the management of constipation in patients with advanced, progressive illness","volume":"40","author":"Librach","year":"2010","journal-title":"J Pain Symptom Manage"},{"issue":"suppl 7","key":"10.1016\/j.amjmed.2018.02.038_bib0025","doi-asserted-by":"crossref","first-page":"vii139","DOI":"10.1093\/annonc\/mds233","article-title":"Management of cancer pain: ESMO Clinical Practice Guidelines","volume":"23","author":"Ripamonti","year":"2012","journal-title":"Ann Oncol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0030","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1016\/S1470-2045(12)70040-2","article-title":"Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC","volume":"13","author":"Caraceni","year":"2012","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0035","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1365-2141.2011.08574.x","article-title":"Guidelines for supportive care in multiple myeloma 2011","volume":"154","author":"Snowden","year":"2011","journal-title":"Br J Haematol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0040","series-title":"Naloxegol for Treating Opioid-Induced Constipation. Technology Appraisal Guidance; no. 345","author":"National Institute for Health and Care Excellence (NICE)","year":"2015"},{"issue":"5","key":"10.1016\/j.amjmed.2018.02.038_bib0045","article-title":"Laxatives for the management of constipation in people receiving palliative care","author":"Candy","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"issue":"suppl 2","key":"10.1016\/j.amjmed.2018.02.038_bib0050","doi-asserted-by":"crossref","first-page":"S2232","DOI":"10.1016\/j.jtho.2017.09.1518","article-title":"Effectiveness of methylnaltrexone bromide in opioid-induced constipation in advanced NSCLC patients","volume":"12","author":"Dimitroulis","year":"2017","journal-title":"J Thorac Oncol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0055","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1001\/jama.283.3.367","article-title":"Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial","volume":"283","author":"Yuan","year":"2000","journal-title":"JAMA"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0060","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.pain.2007.11.008","volume":"137","author":"Webster","year":"2008","journal-title":"Pain"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0065","doi-asserted-by":"crossref","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":"10.1016\/j.amjmed.2018.02.038_bib0070","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1056\/NEJMoa0707377","article-title":"Methylnaltrexone for opioid-induced constipation in advanced illness","volume":"358","author":"Thomas","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0075","first-page":"39","article-title":"Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients","volume":"7","author":"Slatkin","year":"2009","journal-title":"J Support Oncol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0080","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jpainsymman.2007.12.005","article-title":"Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study","volume":"35","author":"Portenoy","year":"2008","journal-title":"J Pain Symptom Manage"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0085","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jpain.2004.12.001","article-title":"Alvimopan: An oral, peripherally acting, \u00b5-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction\u2014A 21-day treatment-randomized clinical trial","volume":"6","author":"Paulson","year":"2005","journal-title":"J Pain"},{"issue":"suppl 6","key":"10.1016\/j.amjmed.2018.02.038_bib0100","first-page":"1466","article-title":"Treatment of opioid-induced constipation with naldemedine in patients with cancer: onset of action in a randomized phase 3 trial","volume":"27","author":"Murata","year":"2016","journal-title":"Ann Oncol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0105","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0885-3924(01)00369-4","article-title":"Low-dose oral naloxone reverses opioid-induced constipation and analgesia","volume":"23","author":"Liu","year":"2002","journal-title":"J Pain Symptom Manage"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0110","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.eururo.2014.02.036","article-title":"Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial","volume":"66","author":"Lee","year":"2014","journal-title":"Eur Urol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0115","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/j.juro.2013.12.015","article-title":"Alvimopan, a peripherally acting \u00b5-opioid receptor antagonist, is associated with reduced costs after radical cystectomy: economic analysis of a phase 4 randomized, controlled trial","volume":"191","author":"Kauf","year":"2014","journal-title":"J Urol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0120","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1200\/JCO.2016.70.8453","article-title":"Phase IIb, randomized, double-blind, placebo-controlled study of naldemedine for the treatment of opioid-induced constipation in patients with cancer","volume":"35","author":"Katakami","year":"2017","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0125","doi-asserted-by":"crossref","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"},{"issue":"4 suppl","key":"10.1016\/j.amjmed.2018.02.038_bib0130","first-page":"e767","article-title":"1870 Alvimopan, a peripherally acting mu-opioid receptor antagonist, accelerates gastrointestinal recovery and decreases length of hospital stay after radical cystectomy","volume":"189","author":"Kamat","year":"2013","journal-title":"J Urol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0135","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jpain.2010.06.012","article-title":"A randomized, placebo-controlled phase 3 trial (Study SB-767905\/012) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain","volume":"12","author":"Jansen","year":"2011","journal-title":"J Pain"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0140","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jpain.2010.06.013","article-title":"A randomized, placebo-controlled phase 3 trial (Study SB-767905\/013) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain","volume":"12","author":"Irving","year":"2011","journal-title":"J Pain"},{"issue":"15 suppl","key":"10.1016\/j.amjmed.2018.02.038_bib0145","doi-asserted-by":"crossref","first-page":"10016","DOI":"10.1200\/JCO.2016.34.15_suppl.10016","article-title":"Phase 3 study to evaluate the efficacy and safety of naldemedine for the treatment of opioid-induced constipation (OIC) in cancer patients","volume":"34","author":"Harada","year":"2016","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0150","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/ejp.1054","article-title":"A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160\/80\u00a0mg daily) vs oxycodone PR","volume":"21","author":"Dupoiron","year":"2017","journal-title":"Eur J Pain"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0155","series-title":"Entereg (alvimopan) package insert","author":"Cubist Pharmaceuticals U.S.","year":"2015"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0160","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.jpainsymman.2009.02.234","article-title":"Methylnaltrexone treatment of opioid-induced constipation in patients with advanced illness","volume":"38","author":"Chamberlain","year":"2009","journal-title":"J Pain Symptom Manage"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0165","first-page":"823","article-title":"Long-term safety and efficacy of oxycodone\/naloxone prolonged-release tablets in patients with moderate-to-severe chronic cancer pain","volume":"23","author":"Ahmedzai","year":"2014","journal-title":"Support Care Cancer"},{"issue":"2","key":"10.1016\/j.amjmed.2018.02.038_bib0170","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.jpainsymman.2017.08.022","article-title":"Drugs for treating opioid-induced constipation: a mixed treatment comparison network meta-analysis of randomized controlled clinical trials","volume":"55","author":"Sridharan","year":"2018","journal-title":"J Pain Symptom Manage"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0175","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijsu.2015.11.013","article-title":"Effect of alvimopan on accelerates gastrointestinal recovery after radical cystectomy: A systematic review and meta-analysis","volume":"25","author":"Cui","year":"2016","journal-title":"Int J Surg"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0180","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1080\/00325481.2016.1149017","article-title":"Efficacy of methylnaltrexone for the treatment of opiod-induced constipation: a meta-analysis and systematic review","volume":"128","author":"Mehta","year":"2016","journal-title":"Postgrad Med"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0185","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1038\/ajg.2013.169","article-title":"Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and meta-analysis","volume":"108","author":"Ford","year":"2013","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0190","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/papr.12218","article-title":"Efficacy and tolerability of subcutaneous methylnaltrexone in patients with advanced illness and opioid-induced constipation: a responder analysis of 2 randomized, placebo-controlled trials","volume":"15","author":"Nalamachu","year":"2015","journal-title":"Pain Pract"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0195","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1185\/03007995.2014.971355","article-title":"Fixed ratio (2:1) prolonged-release oxycodone\/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives","volume":"30","author":"Koopmans","year":"2014","journal-title":"Curr Med Res Opin"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0200","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1093\/annonc\/mdw317","article-title":"Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer","volume":"27","author":"Janku","year":"2016","journal-title":"Ann Oncol"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0205","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1089\/jpm.2014.0362","article-title":"Fixed-dose subcutaneous methylnaltrexone in patients with advanced illness and opioid-induced constipation: results of a randomized, placebo-controlled study and open-label extension","volume":"18","author":"Bull","year":"2015","journal-title":"J Palliat Med"},{"issue":"3","key":"10.1016\/j.amjmed.2018.02.038_bib0210","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1016\/j.jpainsymman.2017.12.492","article-title":"Possible redundant data in the network meta-analysis of pharmacological therapies for opioid-induced constipation","volume":"55","author":"Burr","year":"2018","journal-title":"J Pain Symptom Manage"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0215","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1136\/bmjspcare-2012-000291","article-title":"Paediatric palliative care: intravenous methylnaltrexone relieves constipation","volume":"3","author":"Yeomanson","year":"2013","journal-title":"BMJ Support Palliat Care"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0220","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1002\/ejp.1050","article-title":"Long-term efficacy and safety of oxycodone-naloxone prolonged-release formulation (up to 180\/90\u00a0mg daily) \u2013 results of the open-label extension phase of a phase III multicenter, multiple-dose, randomized, controlled study","volume":"21","author":"Dupoiron","year":"2017","journal-title":"Eur J Pain"},{"key":"10.1016\/j.amjmed.2018.02.038_bib0225","doi-asserted-by":"crossref","first-page":"j3313","DOI":"10.1136\/bmj.j3313","article-title":"Pharmacological therapies for opioid induced constipation in adults with cancer","volume":"358","author":"Boland","year":"2017","journal-title":"BMJ"}],"container-title":["The American Journal of Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002934318302924?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002934318302924?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T09:14:10Z","timestamp":1757582050000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002934318302924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["S0002934318302924"],"URL":"https:\/\/doi.org\/10.1016\/j.amjmed.2018.02.038","relation":{},"ISSN":["0002-9343"],"issn-type":[{"value":"0002-9343","type":"print"}],"subject":[],"published":{"date-parts":[[2018,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Management of Opioid-Induced Constipation in Patients with Malignancy","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.amjmed.2018.02.038","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}