title: Safety and efficacy of methylnaltrexone in shortening the duration of postoperative ileus following segmental colectomy: results of two randomized, placebo-controlled phase 3 trials.
abstract: OBJECTIVE
  Postoperative ileus contributes to surgical morbidity and is associated with prolonged hospitalization and increased health care costs. The efficacy and safety of the peripherally acting μ-opioid receptor antagonist methylnaltrexone in shortening the duration of postoperative ileus following segmental colectomy was evaluated.
  
  
  METHODS
  Two identically designed, multicenter, double-blind, parallel-group, placebo-controlled studies randomly assigned patients undergoing segmental colectomy (study 1, N = 515; study 2, N = 533) to receive 12 or 24 mg of methylnaltrexone intravenously or placebo every 6 hours starting within 90 minutes of surgery completion, continuing for up to 10 days or up to 24 hours after gastrointestinal recovery. The primary efficacy end point was the time from the end of surgery to the first bowel movement. Safety was evaluated via standard assessments (ie, adverse events and related withdrawals, physical examinations, laboratory tests, vital signs, electrocardiograms) and assessment of surgical complications.
  
  
  RESULTS
  The primary and secondary efficacy outcomes (time to discharge eligibility, time to hospital discharge, and clinically meaningful events of nausea and vomiting following segmental colectomy) did not differ significantly between patients treated with either a dose of methylnaltrexone or with placebo. Rates of adverse events and serious adverse events were comparable across all treatment groups in both studies. The most commonly observed adverse events were nausea, pyrexia, and vomiting.
  
  
  CONCLUSIONS
  Although the efficacy of methylnaltrexone in reducing the duration of postoperative ileus was not demonstrated in these studies, intravenous methylnaltrexone at doses of 12 mg and 24 mg was safe, in general, and well tolerated in postcolectomy patients. The utility of intravenous methylnaltrexone in treating postoperative ileus remains unproven.
authors.affiliation: University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. csyu@amc.seoul.kr
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Yu
authors.forename: Ho-Kyung
authors.initials: HK
authors.lastname: Chun
authors.forename: Nancy
authors.initials: N
authors.lastname: Stambler
authors.forename: Jennifer
authors.initials: J
authors.lastname: Carpenito
authors.forename: Seth
authors.initials: S
authors.lastname: Schulman
authors.forename: Evan
authors.initials: E
authors.lastname: Tzanis
authors.forename: Bruce
authors.initials: B
authors.lastname: Randazzo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003082:Colectomy / Q000009:adverse effects* / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D045823:Ileus / Q000188:drug therapy* / Q000209:etiology; D007275:Injections, Intravenous; 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*; D011183:Postoperative Complications; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone