CLINICAL BOTTOM LINE

Methylnaltrexone improves bowel function in the short term in adults with advanced illness and opioid-induced constipation (OIC), without reducing the opioid’s pain relief effectiveness. This drug treatment for OIC does not appear, compared to a placebo, to increase the risk of serious adverse effects but abdominal pain and flatulence is likely.

CLINICAL SCENARIO

Opioids can cause constipation. As a palliative care nurse, you observe how distressing symptoms of opioid-induced constipation can be. Although laxatives are the first-choice of treatment they may not always work. You have heard that methylnaltrexone – a mu-opioid antagonist (MOA) – works well but may affect opioid analgesia. You decide to review the evidence.

QUESTION

In people receiving palliative care, is methylnaltrexone effective for relieving opioid-induced constipation in comparison to placebo?

SEARCH STRATEGY

PubMed- Clinical Queries (Therapy/Broad): methylnaltrexone AND palliative care

CITATION

Candy B, Jones L, Vickerstaff V, Larkin PJ, Stone P. Mu-opioid antagonists for opioid-induced bowel dysfunction in people with cancer and people receiving palliative care. Cochrane Database of Systematic Reviews 2018, Issue 6. Art. No.: CD006332. DOI:10.1002/14651858.CD006332.pub3.

STUDY SUMMARY

A systematic review to assess the effectiveness and safety of MOAs for opioid-induced bowel dysfunction (OIBD) in palliative care settings. Inclusion criteria were:

Type of study: double-blind, randomised controlled trials (RCTs).

Participants: people with cancer or people at a palliative stage irrespective of disease, or both, on a stable opioid regimen and with OIBD not resolved from taking laxatives. Excluded were studies involving people prescribed MOAs for bowel dysfunction associated with postoperative ileus and participants with constipation because of drug misuse or bowel obstruction.

Intervention: Mu-receptor opioid antagonists – any dose, any route.

Comparison: A different MOA, alternative pharmacological or non-pharmacological intervention, a placebo, or no treatment.

Outcomes:

Primary Outcomes: Efficacy: laxation response (bowel movement) in the first 24 hours and between days one and 14 after first dose; effect on analgesia, adverse events.

Secondary Outcomes: Discontinuing treatment due to adverse events, relief of other constipation-associated symptoms; use of rescue medication for laxation (suppository or enema); quality of life, participant satisfaction and preference.

STUDY VALIDITY

Search Strategy: Comprehensive search strategy to locate published and unpublished studies. No language or date restriction.

Review process: Two authors independently screened the search results for potentially relevant studies, selected the studies, conducted risk of bias assessment and extracted data from primary studies. Disagreements resolved by consensus and third person.

Assessment of risk of bias in included studies: Conducted using the Cochrane ’Risk of bias’ tool.

Overall validity: A good quality review involving studies of varying risk of bias.

STUDY RESULTS

Screening of 633 titles/abstracts and ten full text assessments identified eight eligible studies. Three RCTs (518 participants) evaluated the effectiveness of subcutaneous methylnaltrexone compared to placebo in people with advanced disease, mostly cancer. Settings were inpatients and outpatients of a hospice or hospital, and long-term care facilities. Doses were a single dose, or every other day over a two-week trial duration.

Methylnaltrexone resulted in a statistically significant increase in laxations (bowel movement) within 24 hours of first dose and over two weeks compared to placebo.

Rate of opioid withdrawal was not affected (results not shown). Methylnaltrexone did not increase the likelihood of serious adverse events; there were fewer in the methylnaltrexone group and these appeared unrelated to the trial drug. There was no difference between groups in proportion of adverse event overall (low quality evidence) but participants receiving methylnaltrexone were more likely to experience abdominal pain and flatulence.

Table: Summary of results

Outcomes Risk Ratio (95% CI) Studies (number of participants) NNTB

(95% CI)

Heterogeneity

I2

Rescue-free laxation within 24 hours of the first dose 2.77 (1.91 to 4.04) 2 (287) 3 (2 to 3) 0 %
Rescue-free laxation over two weeks (bowel movement within 4 hours after 4 or more of 7 seven doses) 9.98 (4.96 to 20.09) 2 (305) 2 (2 to 2) 0 %
Serious adverse event 0.59 (0.38 to 0.93) 2 (364) 0 %
Adverse event 1.17 (0.94 to 1.45) 3 (518) 74%
CI – Confidence Interval; NNTB – Number needed to treat for an additional beneficial outcome

 

COMMENTS:

  • Participants continued their laxative regimen, but no rescue laxatives were taken four hours before or after receiving the trial drug.
  • Quality of the evidence for laxation outcomes, effect on analgesia, and serious adverse events was graded as moderate.
  • No studies involved children.
  • Pharmac NZ from January 1 2018 has approved methylnaltrexone for use in people receiving palliative care and for whom oral and rectal treatments for opioid-induced constipation are ineffective, or unable to be tolerated. Funding is subject to Special Authority criteria and DHB Hospital restrictions. Contraindications and cautions apply.

Frith Teka, RN, PGDipHSc, MNurs student, Clinical Nurse Specialist – Long-term Conditions, Whanganui DHB; Cynthia Wensley RN, PhD. Lecturer, School of Nursing, University of Auckland c.wensley@auckland.ac.nz

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