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Naldemedine versus placebo in opioid-induced constipation: a meta-analysis
  1. Bastian Wobbe1,
  2. Maximilian Gerner2 and
  3. Claus-Henning Köhne1
  1. 1 Department of Oncology and Hematology, Klinikum Oldenburg, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany
  2. 2 Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
  1. Correspondence to Dr Bastian Wobbe, Department of Oncology and Hematology, Klinikum Oldenburg, University Clinic, Oldenburg, Germany; wobbe.bastian{at}


Objective Opioid-induced constipation (OIC) is a frequent adverse event among patients receiving chronic pain therapy that is requiring opioids. Naldemedine was approved by the Food and Drug Administration to treat OIC and appears to be more efficient than any other peripherally acting µ-opioid receptor antagonist. This meta-analysis aimed at assessing the available data on naldemedine in terms of efficacy.

Methods We searched the Cochrane Library, PubMed and ClinicalTrials on 24 May 2022 to identify randomised controlled trials (RCTs) comparing naldemedine to placebo among patients reporting OIC.

Results Evaluation of 6 RCTs enrolling 2769 participants showed significantly greater respondence to treatment (OR=2.48; 95% CI: 2.02 to 3.06; p<0.00001), change in weekly spontaneous bowel movements (SBMs) (mean difference=1.45; 95% CI: 1.14 to 1.76; p<0.00001), complete SBMs (mean difference=0.89; 95% CI: 0.62 to 1.17; p<0.00001) and SBMs without straining (mean difference=0.89; 95% CI: 0.61 to 1.17; p<0.00001) for patients treated with naldemedine. We found no difference in numeric pain rating scales after one (mean difference=0.05; 95% CI: −0.22 to 0.31; p=0.73) and two weeks of treatment (mean difference= −0.04; 95% CI: −0.31 to 0.22; p=0.75). Funding and clinical diversity were possible risks of bias.

Conclusions Naldemedine improves a variety of bowel function parameters while preserving analgesia, confirming its efficacy for patients with OIC. However, head-to-head trials are needed to establish naldemedine as treatment of first choice for laxative-refractory OIC.

PROSPERO registration number CRD42022281353.

  • constipation
  • supportive care
  • pain
  • symptoms and symptom management

Data availability statement

Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as online supplemental information.

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  • Contributors All authors were involved in the conception and design of this study. BW and MG performed the literature search. BW wrote the paper. All authors were involved in revising the article critically. All authors approved the final version of the manuscript. BW accepts full responsibility for the finished work, the conduct of the study and is responsible for the overall content as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.