6 Effectiveness of mu-opioid antagonists for opioid-induced bowel dysfunction: findings from a systematic review

Abstract

<h3>Introduction</h3> Opioid-induced bowel dysfunction (OIBD) is a major side effect from opioid use in the treatment for pain in cancer and in palliative care. OIBD may be characterised by constipation, incomplete evacuation, bloating, and gastric reflux. This study is a systematic review that is a partial update from a Cochrane review originally published in 2008. This update focuses on people with cancer and people receiving palliative care. <h3>Aims</h3> A systematic review to assess the effectiveness of mu-opioid antagonists (MOAs) for OIBD in people with cancer and people receiving palliative care. <h3>Method</h3> CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science were searched up to June 2020. We included trials that assessed the effectiveness of MOAs for OIBD in people with cancer and people at a palliative stage. Our primary outcomes were laxation response, effect on analgesia, and adverse events. <h3>Results</h3> We identified ten trials. The MOAs evaluated in comparison with placebo included oral naldemedine (2 trials) for people with cancer and subcutaneous methylnaltrexone (2 trials) for people in palliative care where most participants had advanced cancer. The risk of spontaneous laxations in the medium term (two weeks) in the naldemedine arm was two times greater than those in the placebo arm (RR 2.00, 95%CI 1.59, 2.52) and was ten times greater in the methylnaltrexone arm compared to placebo arm (RR 9.98, 95%CI 4.96, 20.09). There was evidence that naldemedine increased the risk of serious adverse events (RR 3.34, 95%CI 0.85, 13.15). <h3>Conclusion</h3> There was moderate-certainty evidence that people with cancer may have improved bowel function with the use of oral naldemedine and people receiving palliative care may have improved bowel function when using subcutaneous methylnaltrexone. <h3>Impact</h3> In this review update, findings have been strengthened by the addition of two new trials. There is a need for further trials including additional outcomes, multiple centers and head-to-head MOA comparisons.