How safe and effective is methylnaltrexone for the treatment of opioid-induced constipation in advanced illness?

Opioids are frequently used to alleviate pain in patients with advanced medical illness; however, constipation that is at least in part mediated by activation of gastrointestinal mu-opioid receptors is a common complication of this treatment. Methylnaltrexone is a peripherally acting antagonist of mu-opioid receptors that selectively blocks peripheral receptors without affecting the effects of opioids mediated by central receptors. This commentary discusses the findings of a 2-week, double-blind, randomized, placebo-controlled trial that investigated the efficacy and safety of subcutaneous methylnaltrexone in relieving opioid-induced constipation in patients with advanced medical illness. Thomas et al. administered methylnaltrexone or a placebo to patients every other day for 2 weeks. There was a threefold increase in the proportion of patients with laxation within 4 h after methylnaltrexone administration compared with placebo (48% vs 15%, respectively). A 3-month, open-label extension phase demonstrated that methylnaltrexone efficacy was maintained. Patients reported gastrointestinal adverse effects but did not experience centrally mediated withdrawal symptoms or loss of analgesia.