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Evidence summaries

Muopioid Antagonists for Opioidinduced Bowel Dysfunction in Cancer and in Palliative Care

Subcutaneous methylnaltrexone compared to placebo appears to improve bowel function in people receiving palliative care in the short term and over 2 weeks, and oral naldemedine appears to be effective compared to placebo within 2 weeks of administration in inducing laxation in people with cancer where conventional laxatives have failed. Level of evidence: "B"

The quality of evidence is downgraded by study limitations (unclear allocation concealment and blinding, and unclear risk of reporting bias).

Summary

A Cochrane review [Abstract] 1 included 10 studies with a total of 1 343 adult subjects. The aim of the review was to assess the effectiveness and safety of mu-opioid antagonists (MOA) for opioid-induced bowel dysfunction (OIBD) in people with cancer and people receiving palliative care irrespective of the type of terminal disease they experienced. In all studies the majority of participants had a primary diagnosis of cancer. The MOAs evaluated were oral naldemedine and naloxone (alone or in combination with oxycodone), and subcutaneous methylnaltrexone. The studies compared MOAs with placebo, MOAs at different doses, or in combination with other drugs.

Oral naldemedine compared with placebo: In the medium term (over 2 weeks) naldemedine increased the risk of spontaneous laxations (RR 2.00, 95% CI 1.59 to 2.52; 2 studies, n=418; NNTB 3) and the risk of adverse events (RR 1.49, 95% CI 1.19 to 1.87; 2 studies, n=418).

Oral naloxone compared with placebo: There was no reported data on laxation response, patient assessment of bowel status, or adverse events.

Oral naloxone with oxycodone versus oxycodone: There were no reported data on risk of spontaneous laxations. Results were inconsistent in whether naloxone with oxycodone compared to oxycodone only improves patients assessment of bowel status.

Subcutaneous methylnaltrexone compared with placebo: Methylnaltrexone increased the risk of spontaneous laxations within 24 hours (RR 2.97, 95% CI 2.13 to 4.13; 2 studies, n=287; NNTB 3) and in the medium term (RR 8.15, 95% CI 4.76 to 13.95; 2 studies, n=305; NNTB 2). It also improved patient assessment of bowel status (RR 2.32, 95% CI 1.64 to 3.27; 2 studies, n=287). Methylnaltrexone increased the risk of adverse events (RR 1.17, 95% CI 1.05 to 1.30; 3 studies, n=518), but semed to decrease the risk of serious adverse events (RR 0.59, 95% CI 0.38 to 0.93; 2 studies, n=364).

Clinical comments

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    References

    • Candy B, Jones L, Vickerstaff V et al. Mu-opioid antagonists for opioid-induced bowel dysfunction in people with cancer and people receiving palliative care. Cochrane Database Syst Rev 2022;9():CD006332. [PubMed]

Primary/Secondary Keywords