Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study
Portenoy RK, Thomas J, Moehl Boatwright ML, Tran D,
Galasso FL, Stambler N, Von Gunten CF, Israel RJ.
Department of Pain Medicine and Palliative Care,
Beth Israel Medical Center, New York, New York.
J Pain Symptom Manage. 2008 May;35(5):458-68.
ABSTRACTMethylnaltrexone, a peripherally-acting quaternary opioid antagonist, is an investigational treatment for opioid-induced constipation in patients with advanced illness. This randomized, parallel-group, repeated dose, dose-ranging trial included a double-blind phase for one week followed by an open-label phase for a maximum of three weeks. Opioid-treated patients with advanced illness who met criteria for opioid-induced constipation despite laxative therapy were potentially eligible. Double-blind treatment occurred on Days 1, 3, and 5; open-label therapy could be administered as often as every other day. The initial dose range of 1mg, 5mg, or 12.5mg was extended by adding a 20mg group during the study while still maintaining the double blind; the initial open-label dose of 5mg could be titrated. The primary outcome was a laxation response within four hours after the first dose. Thirty-three patients received at least one dose of methylnaltrexone. Only one of 10 patients (10%) who received the 1mg dose experienced laxation within four hours of dosing. The median time to laxation was >48 hours for the 1mg dose group, compared to 1.26 hours for all patients receiving >/=5mg (P=0.0003). There was no apparent dose-response above 5mg. Most adverse events were related to the gastrointestinal system, were mild, and did not lead to discontinuation. In conclusion, methylnaltrexone relieved opioid-induced constipation at doses >/=5mg in patients with advanced illness, and did not reduce analgesia or cause opioid withdrawal symptoms.MNTX
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