Mu-Opioid Antagonists May Improve Bowel Dysfunction in Cancer, Palliative Care

Certain mu-opioid antagonists (MOAs) may improve bowel function within 2 weeks in patients with opoid-induced bowel dysfunction (OIBD) in patients receiving treatment for cancer pain or palliative care, according to review and meta-analysis findings published in Cochrane Databases of Systematic Reviews.

MOAs provide an alternative to laxatives for addressing the constipation, bloating, and reflux (ie, OIBD) that may result from opioid pain treatments. In the current review, researchers updated a 2008 review and analysis assessing the safety and effectiveness of MOAs — including naldemedine or naloxone (alone or in combination with oxycodone) and methylnaltrexone — in the treatment of OIBD, a common occurrence in patients treated with opioids for cancer and other pain.

The reviewers searched CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science databases up to December 2021 for randomized controlled trials that evaluated the effect of MOAs on OIBD in cancer and palliative care, regardless of disease severity.

Primary outcomes were laxation response, analgesia effects, and adverse events (AEs) due to MOAs in those with OIBD.

Overall, 10 trials were included in the review that included a total of 1343 patients with cancer or those receiving palliative care. The studies compared the effects of MOAs, including naldemedine, naloxone plus oxycodone, and methylnaltrexone, vs placebo, or different doses of MOAs, or other drug combinations.

Based on moderate-certainty evidence from 2 trials, the researchers observed that oral naldemedine vs placebo improved OIBD within 2 weeks in adults with any-stage cancer, but increased risk for AEs. There was low-certainty evidence on the risk for serious AEs. Subcutaneous methylnaltrexone vs placebo also improved OIBD within 2 weeks for those receiving palliative care.

Based on low-certainty evidence, naldemedine plus opioids and methylnaltrexone showed an improvement in constipation symptoms. In addition, treatment with these MOAs did not appear to affect pain relief. 

Limitations of the analysis were the low to moderate quality evidence; the design of the studies, with potential underreporting of trial methods; the lack of inclusion of data among children; and limited patient assessment of improvement in bowel function.

“There was moderate‐certainty evidence that naldemedine taken orally improved bowel function within two weeks in adults with cancer and opioid‐induced bowel dysfunction but increased the risk of side effects, and that methylnaltrexone taken as an injection improved bowel function over two weeks in people receiving palliative care,” the study authors concluded. They added that more trials are needed, including those that provide more evaluation of AEs and outcomes that patients rate as important.