Alvimopan:: An oral, peripherally acting, μ-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction -: A 21-day treatment-randomized clinical trial

Alvimopan has been shown to reverse the inhibitory effect of opioids on gastrointestinal transit without affecting analgesia. We evaluated oral alvimopan, 0.5 or 1 mg, versus placebo, once daily for 21 days, in 168 patients with opioid-induced bowel dysfunction (011313) who were receiving chronic opioid therapy (minimum, 1 month) for nonmalignant pain (n = 148) or opioid dependence (n = 20). The primary outcome was the proportion of patients having at least one bowel movement (BM) within 8 hours of study drug on each day during the 21-day treatment period. Averaged over the 21-day treatment period, 54%, 43%, and 29% of patients had a BM within 8 hours after alvimopan 1 mg, 0.5 mg, or placebo, respectively (P <.001). Secondary outcomes of median times to first BM were 3, 7, and 21 hours after initial doses of 1 mg, 0.5 mg, and placebo, respectively (P <.001; 1 mg vs placebo). Weekly BMs and overall patient satisfaction were increased after the 1-mg dose (P <.001 at weeks 1 and 2 vs placebo, and P =.046, respectively). Treatment-emergent adverse events were primarily bowel-related, occurred during the first week of treatment, and were of mild to moderate severity. Alvimopan was generally well tolerated and did not antagonize opioid analgesia. Perspective: Patients treated with chronic opioid therapy often experience opioid-induced bowel dysfunction as a result of undesirable effects on peripheral opioid receptors located in the gastrointestinal tract. Alvimopan, a novel peripheral opioid p-receptor antagonist, has demonstrated significant efficacy for the management of opioid-induced bowel dysfunction without compromise of centrally mediated opioid-induced analgesia. (c) 2005 by the American Pain Society.