title: Subcutaneous methylnaltrexone for treatment of acute opioid-induced constipation: phase 2 study in rehabilitation after orthopedic surgery.
abstract: BACKGROUND
  Methylnaltrexone has been shown to be effective for treating opioid-induced constipation (OIC) in chronic settings, but its effects on acute OIC have not been studied.
  
  
  OBJECTIVE
  To assess safety and efficacy of subcutaneous methylnaltrexone in patients with acute OIC after orthopedic procedures.
  
  
  METHODS
  Double-blind, randomized, parallel-group, placebo-controlled, hypothesis-generating phase 2 study.
  
  
  METHODS
  Sixteen US hospitals and rehabilitation facilities.
  
  
  METHODS
  Adult patients with acute OIC after orthopedic surgical procedure, expected to require opioids for at least 7 days postrandomization.
  
  
  METHODS
  Patients received once-daily subcutaneous methylnaltrexone 12 mg or placebo for up to 4 or 7 days.
  
  
  METHODS
  All endpoints were exploratory and included the percentage of patients achieving laxation within 2 and 4 hours of first dose and time to laxation.
  
  
  RESULTS
  Thirty-three patients received at least 1 dose of study drug (methylnaltrexone, n = 18; placebo, n = 15). Within 2 and 4 hours, significantly more patients receiving methylnaltrexone achieved laxation (2 hours: 33.3% vs 0%, P = 0.021; 4 hours: 38.9% vs 6.7%, P = 0.046) compared with placebo. Time to laxation was significantly shorter with methylnaltrexone (median = 15.8 hours) versus placebo (median = 50.9 hours), P = 0.0197. The most common adverse events related to the gastrointestinal tract. Pain scores remained stable and were similar to those of placebo, and signs and symptoms of opioid withdrawal did not emerge in patients receiving methylnaltrexone.
  
  
  CONCLUSIONS
  Methylnaltrexone was generally well tolerated and was active in inducing laxation in this study of patients experiencing acute OIC following orthopedic surgery.
authors: Department of Orthopaedic Surgery, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71130-3932, USA. Laniss@lsuhsc.edu
authors: Lucas
authors: L
authors: Anissian
authors: Harry W
authors: HW
authors: Schwartz
authors: Kevin
authors: K
authors: Vincent
authors: Heather K
authors: HK
authors: Vincent
authors: Jennifer
authors: J
authors: Carpenito
authors: Nancy
authors: N
authors: Stambler
authors: Tage
authors: T
authors: Ramakrishna
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects*; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D019637:Orthopedic Procedures; D010865:Pilot Projects; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage; D012046:Rehabilitation / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone