title: Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms.
abstract: BACKGROUND
  Methylnaltrexone, a selective peripheral acting mu-opioid receptor antagonist, alleviates the constipating effects of opioids without affecting centrally mediated analgesia.
  
  
  OBJECTIVE
  To assess the effect of subcutaneous (SC) methylnaltrexone injection on patient-reported constipation symptoms and pain scores.
  
  
  METHODS
  A total of 469 subjects on opioids for chronic non-malignant pain with opioid-induced constipation were randomized to methylnaltrexone SC with once daily (QD) or every other day (QOD) dosing or placebo for 4 weeks. Constipation symptoms and pain were assessed using the patient assessment of constipation-symptoms (PAC-SYM) questionnaire and a 11-point scale, respectively, at baseline, Day 14 and Day 28. Change from baseline in PAC-SYM and pain scores were compared between methylnaltrexone and placebo arms at Day 28 using analysis of covariance, with treatment group as factor and baseline score as covariate.
  
  
  RESULTS
  A majority of patients were women (60%), average age was 49 years old, and back pain (60%) was the primary pain condition. At Day 28, the methylnaltrexone SC QD group showed a significant improvement over placebo for rectal symptoms (-0.56 vs. -0.30; P < 0.05), stool symptoms (-0.76 vs. -0.43; P < 0.001) and global scores (-0.62 vs. -0.37; P < 0.001). Improvement in stool symptoms (-0.69 vs.-0.43; P < 0.05) and the global scores (-0.52 vs. -0.37; P < 0.05) were significantly greater than placebo in the methylnaltrexone QOD group. Differences in change from baseline in abdominal symptoms and pain scores between the methylnaltrexone SC QD or QOD dosing arms and placebo were not significant.
  
  
  CONCLUSIONS
  The results of our study indicate significant improvement in constipation symptoms with methylnaltrexone QD or QOD dosing compared to placebo without a significant effect on pain scores.
authors.affiliation: Pfizer Inc, Collegeville, PA, USA. shrividya.iyer@pfizer.com
authors.forename: Shrividya S
authors.initials: SS
authors.lastname: Iyer
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Randazzo
authors.forename: Evan L
authors.initials: EL
authors.lastname: Tzanis
authors.forename: Seth L
authors.initials: SL
authors.lastname: Schulman
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Wenjin
authors.initials: W
authors.lastname: Wang
authors.forename: Amy L
authors.initials: AL
authors.lastname: Manley
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D001416:Back Pain / Q000188:drug therapy; D002908:Chronic Disease; 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 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone