title: Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction--a 21-day treatment-randomized clinical trial.
abstract: 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.
authors.affiliation: VA Medical Center, Richmond, USA. Daniel.Paulson@sanofi-aventis.com
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Paulson
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Kennedy
authors.forename: Roger A
authors.initials: RA
authors.lastname: Donovick
authors.forename: Randall L
authors.initials: RL
authors.lastname: Carpenter
authors.forename: Maryann
authors.initials: M
authors.lastname: Cherubini
authors.forename: Lee
authors.initials: L
authors.lastname: Techner
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Yuju
authors.initials: Y
authors.lastname: Ma
authors.forename: William K
authors.initials: WK
authors.lastname: Schmidt
authors.forename: Bruce
authors.initials: B
authors.lastname: Wallin
authors.forename: David
authors.initials: D
authors.lastname: Jackson
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000009:adverse effects*; D002400:Cathartics / Q000008:administration & dosage; D002908:Chronic Disease; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D002400:Cathartics; D010880:Piperidines; D017450:Receptors, Opioid, mu; C419502:alvimopan