title: Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients With Chronic Noncancer Pain: A Placebo Crossover Analysis.
abstract: OBJECTIVE
  In patients with chronic noncancer pain, subcutaneous methylnaltrexone for opioid-induced constipation (OIC) was examined in a randomized controlled trial (RCT) followed by an open-label extension (OLE). This study examined the reproducibility of RCT findings by analyzing data from placebo-treated patients who crossed over to methylnaltrexone.
  
  
  METHODS
  Adults with less than 3 weekly rescue-free bowel movements (RFBMs), taking 50 mg or more of an oral morphine equivalent per day, were randomized to receive methylnaltrexone 12 mg or placebo for 4 weeks, followed by open-label methylnaltrexone 12 mg as needed for 8 weeks.
  
  
  RESULTS
  A total of 134 placebo-treated patients (median morphine equivalent dose, 150 mg/d; mean of 1.1 RFBM per week) crossed over to methylnaltrexone in OLE. During the RCT, 9.7% of placebo-treated patients experienced an RFBM within 4 hours of first dose and 9.0% of all placebo injections resulted in an RFBM within 4 hours compared with 45.9% and 34.5%, respectively, with methylnaltrexone treatment in the OLE. When expressed as percentage of patients experiencing 3 or more RFBMs per week and a 1-RFBM increase over baseline, weekly values ranged from 35% to 40% during placebo treatment; at week 5 of OLE methylnaltrexone, this percentage increased to more than 70% and remained relatively stable throughout the OLE. The most common adverse events during methylnaltrexone treatment were abdominal pain (9.7% vs 1.5% for placebo) and nausea (5.2% vs 6.7%).
  
  
  CONCLUSIONS
  Findings during placebo treatment further establish the profile of OIC and support that little or no gastrointestinal tolerance develops across time. Findings under open-label conditions established the reproducibility and durability of methylnaltrexone for OIC.
authors.affiliation: From the *Thomas Jefferson University, Philadelphia, PA; and †Salix, a Division of Valeant Pharmaceuticals North America LLC, Bridgewater, NJ.
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Viscusi
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Barrett
authors.forename: Craig
authors.initials: C
authors.lastname: Paterson
authors.forename: William P
authors.initials: WP
authors.lastname: Forbes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects*; D059350:Chronic Pain / Q000175:diagnosis / Q000188:drug therapy*; D003248:Constipation / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone