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      Mu-opioid antagonists for opioid-induced bowel dysfunction in people with cancer and people receiving palliative care

      Author(s): 1 , 1 , 1 , 2 , 3
      Editor(s): Cochrane Pain, Palliative and Supportive Care Group
      Publication date (Electronic):
      Journal: Cochrane Database of Systematic Reviews
      Publisher: Wiley

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          Abstract

          Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of treatment for pain in cancer and in palliative care, resulting in increased morbidity and reduced quality of life.This is an update of two Cochrane reviews. One was published in 2011, Issue 1 on laxatives and methylnaltrexone for the management of constipation in people receiving palliative care; this was updated in 2015 and excluded methylnaltrexone. The other was published in 2008, Issue 4 on mu-opioid antagonists (MOA) for OIBD. In this updated review, we only included trials on MOA (including methylnaltrexone) for OIBD in people with cancer and people receiving palliative care.

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          Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.

          Augusto Caraceni, Geoffrey Hanks, Stein Kaasa … (2012)
          Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Methylnaltrexone for opioid-induced constipation in advanced illness.

            Nancy Stambler, Thomas Cooney, Jay Thomas … (2008)
            Constipation is a distressing side effect of opioid treatment. As a quaternary amine, methylnaltrexone, a mu-opioid-receptor antagonist, has restricted ability to cross the blood-brain barrier. We investigated the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness. A total of 133 patients who had received opioids for 2 or more weeks and who had received stable doses of opioids and laxatives for 3 or more days without relief of opioid-induced constipation were randomly assigned to receive subcutaneous methylnaltrexone (at a dose of 0.15 mg per kilogram of body weight) or placebo every other day for 2 weeks. Coprimary outcomes were laxation (defecation) within 4 hours after the first dose of the study drug and laxation within 4 hours after two or more of the first four doses. Patients who completed this phase were eligible to enter a 3-month, open-label extension trial. In the methylnaltrexone group, 48% of patients had laxation within 4 hours after the first study dose, as compared with 15% in the placebo group, and 52% had laxation without the use of a rescue laxative within 4 hours after two or more of the first four doses, as compared with 8% in the placebo group (P<0.001 for both comparisons). The response rate remained consistent throughout the extension trial. The median time to laxation was significantly shorter in the methylnaltrexone group than in the placebo group. Evidence of withdrawal mediated by central nervous system opioid receptors or changes in pain scores was not observed. Abdominal pain and flatulence were the most common adverse events. Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal. (Clinical Trials.gov number, NCT00402038 [ClinicalTrials.gov].). Copyright 2008 Massachusetts Medical Society.
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              Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden

              S Panchal, P Müller-Schwefe, J Wurzelmann (2007)
              As a result of the undesired action of opioids on the gastrointestinal (GI) tract, patients receiving opioid medication for chronic pain often experience opioid-induced bowel dysfunction (OBD), the most common and debilitating symptom of which is constipation. Based on clinical experience and a comprehensive MEDLINE literature review, this paper provides the primary care physician with an overview of the prevalence, pathophysiology and burden of OBD. Patients with OBD suffer from a wide range of symptoms including constipation, decreased gastric emptying, abdominal cramping, spasm, bloating, delayed GI transit and the formation of hard dry stools. OBD can have a serious negative impact on quality of life (QoL) and the daily activities that patients feel able to perform. To relieve constipation associated with OBD, patients often use laxatives chronically (associated with risks) or alter/abandon their opioid medication, potentially sacrificing analgesia. Physicians should have greater appreciation of the prevalence, symptoms and burden of OBD. In light of the serious negative impact OBD can have on QoL, physicians should encourage dialogue with patients to facilitate optimal symptomatic management of the condition. There is a pressing need for new therapies that act upon the underlying mechanisms of OBD.
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                Author and article information

                Journal
                Title: Cochrane Database of Systematic Reviews
                Publisher: Wiley
                ISSN (Electronic): 14651858
                Publication date (Electronic): June 05 2018
                Affiliations
                [1 ]Marie Curie Palliative Care Research Department, UCL Division of Psychiatry; 6th Floor, Maple House 149 Tottenham Court Road London UK W1T 7NF
                [2 ]UCD College of Health Sciences; UCD School of Nursing, Midwifery and Health Systems and Our Lady's Hospice and Care Services; Dublin Ireland
                [3 ]Marie Curie Palliative Care Research Department, UCL Division of Psychiatry; Division of Psychiatry; Room 119, First Floor, Charles Bell House 67-73 Riding House Street London UK W1W 7EJ
                Article
                DOI: 10.1002/14651858.CD006332.pub3
                PMC ID: 6513061
                PubMed ID: 29869799
                SO-VID: a5fd7d61-a920-4ce2-8a7e-321354beae1b
                Copyright © © 2018
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