Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients

J Support Oncol. 2009 Jan-Feb;7(1):39-46.


Methylnaltrexone, a peripheral mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may relieve opioid-induced constipation (OIC) without reversing analgesia. A total of 154 patients with advanced illness and OIC enrolled in a double-blind, randomized, placebo-controlled trial, with optional open-label phases (up to 4 months) in hospice and palliative care centers during 2003-2005. They received a single subcutaneous injection of methylnaltrexone (0.15 mg/kg or 0.3 mg/kg) or placebo. Laxation response within 4 hours was 62% and 58% for methylnaltrexone 0.15 mg/kg and 0.3 mg/kg, respectively, compared with 14% for placebo (P < 0.0001; each dose vs placebo). Approximately half of the methylnaltrexone responders defecated within 30 minutes of dosing. Open-label phase response rates mirrored those for methylnaltrexone during the double-blind phase.There was no change in pain scores or evidence of central opioid withdrawal.The most common adverse events (AEs) were abdominal pain and flatulence.Three patients had serious AEs attributed to methylnaltrexone. Subcutaneous methylnaltrexone was efficacious in rapidly inducing laxation and was generally well tolerated in patients with advanced illness and OIC.

Trial registration: NCT00401362.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesia / methods
  • Analgesics, Opioid / adverse effects*
  • Constipation / chemically induced
  • Constipation / drug therapy*
  • Critical Illness
  • Defecation / drug effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Naltrexone / analogs & derivatives*
  • Naltrexone / therapeutic use
  • Narcotic Antagonists / therapeutic use*
  • Pain Measurement
  • Quaternary Ammonium Compounds / therapeutic use
  • Receptors, Opioid, mu / drug effects
  • Treatment Outcome


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Quaternary Ammonium Compounds
  • Receptors, Opioid, mu
  • methylnaltrexone
  • Naltrexone

Associated data