title: Methylnaltrexone treatment of opioid-induced constipation in patients with advanced illness.
abstract: Methylnaltrexone, a peripherally acting mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, reverses opioid-induced constipation (OIC) without affecting analgesia. A double-blind study in patients with advanced illness and OIC demonstrated that methylnaltrexone significantly induced laxation within four hours after the first dose compared with placebo. In this study, patients with advanced illness and OIC on stable doses of opioids and laxatives were randomized to methylnaltrexone 0.15mg/kg (n=62) or placebo (n=71) subcutaneously every other day for two weeks. Laxation was assessed daily. Constipation distress, bowel status change, pain, laxative use, and opioid withdrawal symptoms were assessed weekly using standardized scales. Additional analyses to further characterize response to methylnaltrexone revealed that among patients with a bowel movement within four hours following the first dose, the median time to response was 0.5 hours for methylnaltrexone. Response rates among methylnaltrexone-treated patients who had responded to all previous doses were 57%-100% for doses two to seven. Among methylnaltrexone-treated patients who did not respond to the first or to the first two consecutive doses, 35% and 26% responded to the second and third dose, respectively. Higher percentages of patients and clinicians rated bowel status as improved in the methylnaltrexone than the placebo group. Fewer methylnaltrexone than placebo patients reported use of common laxative types, particularly enemas, during the study. Subcutaneous methylnaltrexone promptly and predictably induced laxation, improved constipation distress, and was associated with less laxative use in patients with advanced illness and OIC.
authors.affiliation: Palliative Consulting LLC, Orem, Utah 84097, USA. brucechamb@comcast.net
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Chamberlain
authors.forename: Karen
authors.initials: K
authors.lastname: Cross
authors.forename: Jaron L
authors.initials: JL
authors.lastname: Winston
authors.forename: Jay
authors.initials: J
authors.lastname: Thomas
authors.forename: Wenjin
authors.initials: W
authors.lastname: Wang
authors.forename: Chinyu
authors.initials: C
authors.lastname: Su
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Israel
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D003672:Defecation; D004311:Double-Blind Method; D006801:Humans; D054368:Laxatives / Q000627:therapeutic use; D009271:Naltrexone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010148:Intractable Pain / Q000150:complications / Q000188:drug therapy; D010166:Palliative Care; D000644:Quaternary Ammonium Compounds / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; D054368:Laxatives; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone