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      Patient Preference and Adherence (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the growing importance of patient preference and adherence throughout the therapeutic process. Sign up for email alerts here.

      34,896 Monthly downloads/views I 2.314 Impact Factor I 3.8 CiteScore I 1.14 Source Normalized Impact per Paper (SNIP) I 0.629 Scimago Journal & Country Rank (SJR)

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      Peripherally acting μ-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy

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          Abstract

          Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain. Other treatment options include fixed-dose combination products of oxycodone analgesic together with naloxone.

          Most cited references64

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          Naloxegol for opioid-induced constipation in patients with noncancer pain.

          William Chey, Lynn Webster, Mark Sostek … (2014)
          Opioid-induced constipation is common and debilitating. We investigated the efficacy and safety of naloxegol, an oral, peripherally acting, μ-opioid receptor antagonist, for the treatment of opioid-induced constipation.
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            Incidence, prevalence, and management of opioid bowel dysfunction.

            M. Pappagallo (2001)
            Opioid bowel dysfunction (OBD) is a common adverse effect associated with opioid therapy. OBD is commonly described as constipation; however, it is a constellation of adverse gastrointestinal (GI) effects, which also includes abdominal cramping, bloating, and gastroesophageal reflux. The mechanism for these effects is mediated primarily by stimulation of opioid receptors in the GI tract. In patients with pain, uncontrolled symptoms of OBD can add to their discomfort and may serve as a barrier to effective pain management, limiting therapy, or prompting discontinuation. Patients with cancer may have disease-related constipation, which is usually worsened by opioid therapy. However, OBD is not limited to cancer patients. A recent survey of patients taking opioid therapy for pain of noncancer origin found that approximately 40% of patients experienced constipation related to opioid therapy ( 50% of the time. Laxatives prescribed prophylactically and throughout opioid therapy may improve bowel movements in many patients. Nevertheless, a substantial number of patients will not obtain adequate relief of OBD because of its refractory nature. Naloxone and other tertiary opioid receptor antagonists effectively reduce the symptoms of constipation in opioid-treated patients. However, because they also act centrally, they may provoke opioid withdrawal symptoms or reverse analgesia in some patients. There are 2 peripherally selective opioid receptor antagonists, methylnaltrexone and ADL 8-2698 (Adolor Corporation, Exton, PA, USA), that are currently under investigation for their use in treating OBD. Early studies confirm that they are effective at normalizing bowel function in opioid-treated patients without entering the central nervous system and affecting analgesia. With a better understanding of the prevalence of OBD and its pathophysiology, a more aggressive approach to preventing and treating OBD is possible and will likely improve the quality of life of patients with pain.
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              A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.

              Gary Lissner, Joachim Nadstawek, Stefan Wirz … (2008)
              Opioid-induced constipation can have a major negative impact on patients' quality of life. This randomised, double-blinded study evaluated the analgesic efficacy of prolonged-release (PR) oral oxycodone when co-administered with PR oral naloxone, and its impact on opioid-induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone. A total of 202 patients with chronic pain (mainly non-cancer related, 2.5% of patients had cancer-related pain) under stable oral oxycodone therapy (40, 60 or 80 mg/day) were randomised to receive 10, 20, 40 mg/day naloxone or placebo. After a 4-week maintenance phase, patients received oxycodone only for 2 weeks. Pain intensity was evaluated using a numerical analogue scale and bowel function was assessed using the bowel function index. No loss of analgesic efficacy with naloxone was observed. Mean pain intensity scores on randomisation were comparable for placebo, 10mg, 20mg and 40 mg naloxone dose, and remained unchanged during treatment. Bowel function improved with increasing naloxone dose. Naloxone 20mg and 40 mg significantly improved bowel function at the end of the maintenance phase compared with placebo (p<0.05). Overall, the combination was well tolerated, with no unexpected adverse events. There was a trend towards an increased incidence of diarrhoea with higher doses of naloxone. The 2:1 oxycodone/naloxone ratio was identified as the most suitable for further development. Co-administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Patient Prefer Adherence
                Journal ID (iso-abbrev): Patient Prefer Adherence
                Journal ID (publisher-id): Patient Preference and Adherence
                Title: Patient preference and adherence
                Publisher: Dove Medical Press
                ISSN (Electronic): 1177-889X
                Publication date Collection: 2017
                Publication date (Electronic): 17 January 2017
                Volume: 11
                Pages: 107-119
                Affiliations
                [1 ]NEMA Research, Inc., Naples, FL
                [2 ]University of Arizona College of Pharmacy, University of Arizona, Tucson, AZ
                [3 ]Temple University School of Pharmacy, Temple University, Philadelphia, PA
                [4 ]Department of Medicine, Albert Einstein College of Medicine, New York, NY
                [5 ]Department of Medicine, St. Luke’s Hospital, Cleveland, OH, USA
                Author notes
                Correspondence: Joseph V Pergolizzi Jr, NEMA Research, Inc., 868-106 Avenue N, Naples, FL 34108, USA, Tel +1 239 597 3564, Email jpjmd@ 123456msn.com
                Article
                Publisher ID: ppa-11-107
                DOI: 10.2147/PPA.S78042
                PMC ID: 5261842
                PubMed ID: 28176913
                SO-VID: c529ced5-ceb9-49d9-8ed2-549dc04a93d3
                Copyright © © 2017 Pergolizzi Jr et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Subject: Review

                ScienceOpen disciplines: Medicine
                Keywords: opioid-induced constipation,opioid bowel disorder,pamora,peripherally acting mu-opioid receptor antagonist,noncancer pain patients,opioid-associated side effects
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: opioid-induced constipation, opioid bowel disorder, pamora, peripherally acting mu-opioid receptor antagonist, noncancer pain patients, opioid-associated side effects

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