Level 2: Mid-level evidence

Methylnaltrexone bromide (Relistor) is FDA-approved to help restore bowel function in patients with opioid-induced constipation in late-stage, advanced illness (FDA Press Release. April 24, 2008). A randomized trial evaluated the efficacy of subcutaneous (SC) methylnaltrexone in 134 patients with advanced illness who received opioids for at least two weeks and laxatives for at least three days without relief of opioid-induced constipation (N Engl J Med. 2008;358:2332-2343). Advanced illness was defined as terminal disease (incurable cancer or other end-stage disease) with life expectancy of one month or more. Patients were randomized to methylnaltrexone 0.15 mg/kg SC every other day for two weeks or to placebo. The assigned treatment dose was doubled after one week if a patient had fewer than three bowel movements without a laxative. One patient who received unblinded methylnaltrexone was excluded from the efficacy analysis.

Compared with placebo, methylnaltrexone yielded a higher rate of bowel movement without laxative within four hours of first dose (48% vs. 15%, P<.001, NNT 3), within four hours after two or more of the first four doses (52% vs. 8%, P<.001, NNT 3), within four hours after four or more of the first seven doses (39% vs. 6%, P<.001, NNT 3), and after one or more of seven doses (79% vs. 46%, NNT 3). The response rate with individual doses ranged from 37%-48% with methylnaltrexone vs. 7%-15% with placebo. A bowel movement without a laxative with-in 24 hours after each of seven doses occurred in 55%-66% vs. 29%-39%; three or more laxative-free bowel movements per week occurred in 68% vs. 45% (P <.009, NNT 5). The median time to a bowel movement after the first dose was 6.3 hours vs. >48 hours (P <.001).

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There were no significant differences in withdrawal scores or changes in pain. Adverse effects that were more common with methylnaltrexone included abdominal pain (17% vs. 13%, NNH 25), flatulence (13% vs. 7%, NNH 16), nausea (11% vs. 7%, NNH 25), increased body temperature (8% vs. 3%, NNH 20), and dizziness (8% vs. 3%, NNH 20).