The Efficacy of Peripheral Opioid Antagonists in Opioid-Induced Constipation and Postoperative Ileus: A Systematic Review of the Literature

Reg Anesth Pain Med. 2017 Nov/Dec;42(6):767-777. doi: 10.1097/AAP.0000000000000671.


Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective μ-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting μ-opioid receptor antagonists target the μ-opioid receptor without reversing analgesia. Three such agents are US Food and Drug Administration approved. We reviewed the literature for randomized controlled trials that studied the efficacy of alvimopan, methylnaltrexone, and naloxegol in treating either opioid-induced constipation or postoperative ileus. Peripherally acting μ-opioid receptor antagonists may be effective in treating both opioid-induced bowel dysfunction and postoperative ileus, but definitive conclusions are not possible because of study inconsistency and the relatively low quality of evidence. Comparisons of agents are difficult because of heterogeneous end points and no head-to-head studies.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Constipation / chemically induced*
  • Constipation / diagnosis
  • Constipation / drug therapy*
  • Humans
  • Ileus / diagnosis
  • Ileus / drug therapy*
  • Ileus / etiology
  • Narcotic Antagonists / administration & dosage*
  • Postoperative Complications / diagnosis
  • Postoperative Complications / drug therapy*
  • Postoperative Complications / etiology
  • Randomized Controlled Trials as Topic / methods


  • Analgesics, Opioid
  • Narcotic Antagonists