Methylnaltrexone

Methylnaltrexone is a selective mu-opioid receptor antagonist that has restricted ability to cross the blood-brain barrier, thus enabling reversal of opioid-induced peripheral effects, such as constipation, without affecting the central effects, such as pain relief. Treatment with subcutaneous methylnaltrexone 0.15-0.30 mg/kg, relative to placebo, significantly increased the rescue-free laxation response rate within 4 hours of the first dose (primary endpoint) in adult patients with opioid-induced constipation and advanced illness in two randomized, double-blind, placebo-controlled, multicentre, phase III studies; one was a single-dose study (n = 154), the other a multiple-dose study (n = 133). In the multiple-dose study, rescue-free laxation response rates within 4 hours after at least two of the first four doses (coprimary endpoint) were also significantly higher in methylnaltrexone recipients than in placebo recipients. Moreover, median time to laxation after the first dose was significantly shorter in methylnaltrexone recipients than in placebo recipients in both studies. Methylnaltrexone was not associated with any significant changes in pain scores or central opioid withdrawal in these studies. Methylnaltrexone was generally well tolerated in clinical trials; most adverse events were of mild to moderate severity.