Related Experiment Video
Updated: Jun 1, 2026
A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training
Published on: January 29, 2017
Methylnaltrexone for opioid-induced constipation in patients with advanced illness: a 3-month open-label treatment
Arthur G Lipman1, Sloan Karver, Gail Austin Cooney
1Pain Management Center, University of Utah, Salt Lake City, Utah, USA. arthur.lipman@utah.edu
Abstract:
Methylnaltrexone is a methylated form of the mu-opioid antagonist naltrexone that blocks peripheral effects of opioids without affecting centrally mediated analgesia. The authors conducted a 3-month open-label extension trial of methylnaltrexone in patients with advanced illness and opioid-induced constipation (OIC). Following completion of a 2-week double-blind (DB) trial, 82 patients with OIC who did not respond to laxatives received subcutaneous (SC) methylnaltrexone as needed for up to 3 months. Patients received 0.15 mg/kg as a first dose, adjusted to 0.3 mg/kg or 0.075 mg/kg as needed (maximum of one dose per 24 hours). Mean laxation response (rescue-free bowel movement within 4 hours) rates (DB phase, months 1, 2, 3 open-label phase) were 45.3%, 45.5%, 57.7%, and 57.3%, respectively, for patients treated with DB methylnaltrexone and 10.8%, 48.3%, 47.6%, and 52.1%, respectively, for patients treated with DB placebo. Median time to laxation among responders was 45 minutes (range 0-4 hours) for all doses. Approximately 50% of patients reported improvement in constipation distress. Patient and investigator global clinical impression of change scores also improved. There were minimal changes in pain scores and opioid withdrawal symptoms. Adverse events included abdominal pain and nausea, mostly mild or moderate in severity. SC methylnaltrexone administered PRN (as needed) for up to 3 months continued to rapidly induce laxation in advanced illness patients with OIC.
Insights
Methylnaltrexone effectively treats opioid-induced constipation (OIC) in advanced illness patients. This study shows subcutaneous methylnaltrexone administered as needed rapidly induces laxation with minimal impact on pain or withdrawal.
Area of Science:
- Pharmacology
- Gastroenterology
- Palliative Care
Background:
- Opioid-induced constipation (OIC) is a common and distressing side effect in patients with advanced illness.
- Standard laxatives are often ineffective for OIC, necessitating alternative treatment strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of subcutaneous methylnaltrexone administered as needed (PRN) for up to 3 months in patients with advanced illness and OIC.
- To assess the impact of methylnaltrexone on laxation response, constipation distress, and overall clinical impression.
Main Methods:
- An open-label extension trial involving 82 patients with OIC who did not respond to laxatives.
- Patients received subcutaneous methylnaltrexone PRN, with flexible dosing (0.075-0.3 mg/kg, max one dose/24 hours).
- Laxation response was defined as a rescue-free bowel movement within 4 hours.
Main Results:
- Mean laxation response rates were consistently around 45-57% across the study duration for methylnaltrexone treatment.
- Median time to laxation among responders was 45 minutes.
- Approximately 50% of patients reported improved constipation distress, with positive global clinical impression scores.
Conclusions:
- Subcutaneous methylnaltrexone administered PRN is effective in rapidly inducing laxation in advanced illness patients with OIC.
- The treatment demonstrates an acceptable safety profile, with mild to moderate adverse events like abdominal pain and nausea.
- Methylnaltrexone offers a valuable therapeutic option for managing OIC in palliative care settings.
Related Concept Videos
01:21Drugs for Treatment of Constipation-Predominant IBS
01:17Drugs for Treatment of Diarrhea-Predominant IBS
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
01:17Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:20Drugs Affecting GI Tract Motility: Other Laxatives
Osmotic or saline laxatives, like magnesium hydroxide or milk of...