title: Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic, nonmalignant pain: a randomized controlled study.
abstract: Methylnaltrexone is effective for opioid-induced constipation (OIC) in advanced illness patients. This 4-week, double-blind, randomized, placebo-controlled study investigated the effect of subcutaneous methylnaltrexone on OIC in patients receiving opioids for chronic, nonmalignant pain. Patients (N = 460) received subcutaneous methylnaltrexone 12 mg once daily (QD) or every other day (alternating with placebo) compared with placebo. Assessments included bowel movement count, time of bowel movement, straining, sense of complete evacuation, Bristol Stool Form Scales, and quality of life. Within 4 hours of first dose, 34.2% of patients in both methylnaltrexone groups had rescue-free bowel movements (RFBMs) versus 9.9% on placebo (P < .001). The estimated number needed to treat was about 4. On average, 28.9% of methylnaltrexone QD and 30.2% of methylnaltrexone alternate-day dosing resulted in RFBMs within 4 hours versus 9.4% QD and 9.3% alternate-day placebo injections (both P < .001). Both methylnaltrexone groups had significantly shorter time to first RFBM (P < .001) and greater increase in number of weekly RFBMs (P < .05) versus placebo. Adverse events included abdominal pain, diarrhea, nausea, and hyperhidrosis. Bristol Stool Form Scale scores (P = .002) and sensation of complete evacuation (P < .04) were significantly superior with methylnaltrexone QD; both methylnaltrexone groups reported no or mild straining during RFBMs in the first 2 weeks (P < .02). At 4 weeks, a significantly greater improvement in patient-reported, constipation-specific quality of life was seen in the alternate-day dosing (P < .05) and QD (P < .001) groups.
  
  
  CONCLUSIONS
  We present data demonstrating that subcutaneous methylnaltrexone 12 mg given once daily (QD) or every other day provides significant relief of OIC and was generally well tolerated in patients with chronic, nonmalignant pain. These results expand on prior effectiveness observed for the treatment of OIC in advanced illness patients to a broader population.
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. emichna@partners.org
authors.forename: Edward
authors.initials: E
authors.lastname: Michna
authors.forename: E Richard
authors.initials: ER
authors.lastname: Blonsky
authors.forename: Seth
authors.initials: S
authors.lastname: Schulman
authors.forename: Evan
authors.initials: E
authors.lastname: Tzanis
authors.forename: Amy
authors.initials: A
authors.lastname: Manley
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Shrividya
authors.initials: S
authors.lastname: Iyer
authors.forename: Bruce
authors.initials: B
authors.lastname: Randazzo
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects*; D016009:Chi-Square Distribution; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D003672:Defecation / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone