title: Off-label uses of alvimopan and methylnaltrexone.
abstract: OBJECTIVE
  Off-label uses of the peripheral μ-opioid receptor antagonists alvimopan and methylnaltrexone are reviewed.
  
  
  CONCLUSIONS
  Alvimopan is approved by the Food and Drug Administration (FDA) for postoperative ileus after surgeries that include partial bowel resection with primary anastomosis, while methylnaltrexone is approved for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care. Literature describing the off-label use of alvimopan in the treatment of OIC and of methylnaltrexone in postoperative ileus was reviewed and included retrospective studies and prospective Phase II-IV trials. Randomized controlled trials did not demonstrate consistent benefit of alvimopan in OIC nor of methylnaltrexone in postoperative ileus. A greater proportion of patients receiving alvimopan for OIC experienced severe adverse cardiovascular events, leading to a risk evaluation and mitigation strategy and discontinuation of its study in this condition. Data are limited and unreplicated for the off-label use of alvimopan for postoperative ileus in patients undergoing abdominal hysterectomy. Individual studies suggest benefit with methylnaltrexone for OIC in unlabeled populations, including patients with non-cancer-related pain, opioid dependence, opioid sedation, and opioid use after orthopedic surgery; however, confirmatory evaluations have not been performed.
  
  
  CONCLUSIONS
  Trials of alvimopan in the FDA-approved use of methylnaltrexone (OIC) indicate potentially serious cardiovascular safety concerns and conflicting findings of efficacy. Similarly, trials of methylnaltrexone in the FDA-approved use of alvimopan (postoperative ileus) consistently showed no benefit. Evaluations of both drugs in their labeled conditions in populations not endorsed in their product labeling have been limited and largely unreplicated.
authors.affiliation: Ryan W. Rodriguez, Pharm.D., BCPS, is Clinical Assistant Professor, Drug Information Specialist, University of Illinois at Chicago College of Pharmacy, Chicago, IL (rwrodrig@uic.edu).
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Rodriguez
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D045823:Ileus / Q000188:drug therapy*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D056687:Off-Label Use; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000188:drug therapy; D000644:Quaternary Ammonium Compounds / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; D005765:Gastrointestinal Agents; D009292:Narcotic Antagonists; D010880:Piperidines; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone; C419502:alvimopan