Chamberlain, B.H., Cross, K., Winston, J.L., Thomas, J., Wang, W., Su, C., & Israel, R.J. (2009). Methylnaltrexone treatment of opioid-induced constipation in patients with advanced illness. Journal of Pain and Symptom Management, 38, 683-690.

To describe laxative response to subcutaneous methylnaltrexone in patients with advanced illness and opioid-induced constipation.

Patients were randomly assigned to receive either methylnaltrexone 0.15 mg/kg or placebo subcutaneously every other day for two weeks. Patients were permitted to continue their baseline laxatives. By day 8, the study drug dose (methylnaltrexone or placebo) could be doubled if patients had fewer than three rescue-free bowel movements (BMs).

• The study reported on a sample of 134 patients.
• Median age was 72 years (range 34-93) for the methylnaltrexone group and 70 years (range 39-98) for the placebo group.
• The sample was 57% female (n = 36) and 43% male (n = 27) in the methylnaltrexone group, and 56% female (n = 40) and 44% male (n = 31) in the placebo group.
• Patients had advanced illness, such as terminal cancer or other end-stage diseases with a life expectancy of at least one month, and opioid-induced constipation.
• More than 50% of the study participants had a diagnosis of terminal cancer.

• Multi-site
• Inpatient
• 27 nursing homes, hospice sites, and palliative care centers
• United States and Canada

The study has clinical applicability for the end-of-life and palliative phases of care.

This was a post-hoc analysis of a two-week double-blind, randomized, placebo-controlled study.

• Global Clinical Impression of Change (GCIC)
• National Cancer Institute common toxicity criteria (NCI CTC), version 2.0
• Numeric pain rating scale (0 = no pain and 10 = worst possible)
• Modified Himmelsbach Withdrawal Scale

• Median time to BM was 0.5 hours in the methylnaltrexone group and 2 hours in the placebo group (p = 0.013).
• More patients in the methylnaltrexone group (75%) than the placebo group (29%) had a laxation response to at least one of the doses (p < 0.0001).
• In the methylnaltrexone group, 73.5% of patients on day 7 and 67.9% on day 14 rated their bowel status as better on the GCIC scale.
• During the study, fewer patients in the methylnaltrexone group than the placebo group reported use of some major classes of laxatives.
• The most common adverse events (AEs) among methylnaltrexone users were abdominal pain, flatulence, and vomiting. Most AEs were Grade 1 or Grade 2 on the NCI CTC.
• Mean total opioid withdrawal scores were unchanged.

Methylnaltrexone 0.15 mg/kg administered subcutaneously every other day was effective in relieving opioid-induced constipation.

Sixteen percent of patients (10 of 62) in the methylnaltrexone group and 24% (17 of 71) in the placebo group did not complete the study.

Subcutaneous methylnaltrexone 0.15 mg/kg appears to be effective in relieving opioid-induced constipation in a timely and predictable manner without reducing pain control or producing symptoms of opioid withdrawal. If an individual does not respond to the first dose, they may still receive some benefit with additional doses. However, the response rate decreased to 25% for individuals receiving a third dose in this study. Reasons for constipation other than opioid use may need to be looked for in nonresponders.