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 (OBD) 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. 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 mu-receptor antagonist, has demonstrated significant efficacy for the management of
opioid-induced bowel dysfunction without compromise of centrally mediated
opioid-induced
analgesia.