Methylnaltrexone

Area of Science:

• Pharmacology
• Gastroenterology
• Oncology

Background:

• Opioid analgesics are crucial for pain management but frequently cause constipation.
• Opioid-induced constipation (OIC) significantly impacts patient quality of life, especially in advanced illness.
• Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist designed to counteract OIC.

Purpose of the Study:

• To evaluate the efficacy and safety of methylnaltrexone in treating OIC in adult patients with advanced illness.
• To assess methylnaltrexone's effect on peripheral opioid-induced constipation without altering central analgesia.

Main Methods:

• Two randomized, double-blind, placebo-controlled, multicentre, phase III studies were conducted.
• Participants received either subcutaneous methylnaltrexone (0.15-0.30 mg/kg) or placebo.
• Primary endpoint: rescue-free laxation response rate within 4 hours of the first dose.

Main Results:

• Methylnaltrexone significantly increased the rescue-free laxation response rate compared to placebo in both single- and multiple-dose studies.
• Median time to laxation was significantly shorter with methylnaltrexone.
• No significant changes in pain scores or central opioid withdrawal symptoms were observed.

Conclusions:

• Subcutaneous methylnaltrexone is an effective treatment for OIC in patients with advanced illness.
• It provides peripheral relief from OIC without compromising central opioid-mediated pain relief.
• Methylnaltrexone was generally well-tolerated with mild to moderate adverse events.