What is Methylnaltrexone (MNTX)?

From the Guidelines

Methylnaltrexone is recommended for the treatment of opioid-induced constipation in patients with advanced illness who have not responded adequately to conventional laxative therapies, at a dose of 0.15 mg per kilogram of body weight administered subcutaneously every other day, as it has been shown to provide effective relief while maintaining pain management. The medication works by blocking opioid receptors in the gastrointestinal tract without affecting pain control, as it cannot cross the blood-brain barrier, allowing it to counteract the constipating effects of opioids while maintaining their analgesic benefits 1.

Key Points

• Methylnaltrexone is a quaternary derivative of naltrexone, approved for use in the treatment of opioid-induced constipation (OIC) in advanced illness and palliative care patients whose response to usual laxative therapy has been insufficient 1.
• The typical dose is 8 mg (for patients weighing 38-61 kg) or 12 mg (for patients weighing 62-114 kg) administered subcutaneously every other day as needed, with dose adjustments for those outside these weight ranges.
• Methylnaltrexone has been shown to be effective in relieving OIC, with most patients achieving defaecation within 90 minutes of administration, and has a low incidence of adverse effects, with only a 0.2% incidence reported 1.
• The medication is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Administration and Dosage

• The dose of methylnaltrexone can be adjusted based on patient response, with the frequency of administration increased to once daily if needed 1.
• The medication should not be used in patients with a postoperative ileus or mechanical bowel obstruction 1.

Efficacy and Safety

• Methylnaltrexone has been shown to be effective in relieving OIC, with a higher stool frequency and less time to laxation compared to placebo, and better patient outcomes and less distress associated with its use 1.
• The medication has a low incidence of adverse effects, with only a 0.2% incidence reported, and is generally well-tolerated by patients 1.

Comparison to Other Treatments

• Methylnaltrexone has been compared to other treatments for OIC, including naloxegol and lubiprostone, and has been shown to be effective in relieving OIC while maintaining pain management 1.

From the FDA Drug Label

1. 1 Mechanism of Action Methylnaltrexone is a selective antagonist of opioid binding at the mu-opioid receptor. As a quaternary amine, the ability of methylnaltrexone to cross the blood-brain barrier is restricted This allows methylnaltrexone to function as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system (CNS).

• Methylnaltrexone's mechanism of action is as a selective antagonist of opioid binding at the mu-opioid receptor.
• It decreases the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system (CNS) by functioning as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract 2.

From the Research

Overview of Methylnaltrexone

• Methylnaltrexone is a selective mu-opioid receptor antagonist that has restricted ability to cross the blood-brain barrier, thus enabling reversal of opioid-induced peripheral effects, such as constipation, without affecting the central effects, such as pain relief 3, 4.
• It is used to treat opioid-induced constipation (OIC) in patients with advanced illness or chronic nonmalignant pain 5, 6, 7.

Efficacy of Methylnaltrexone

• Studies have shown that methylnaltrexone significantly increases the rescue-free laxation response rate within 4 hours of the first dose in adult patients with OIC and advanced illness 4, 6.
• Methylnaltrexone has been found to be effective in inducing laxation in patients with OIC, with a rapid onset of action and improvement maintained for at least 3 months during treatment 3, 6.
• A meta-analysis and systematic review found that methylnaltrexone was associated with a statistically significant increase in rescue-free bowel movements (RFBMs) compared to placebo 5.

Safety and Tolerability

• Methylnaltrexone has been found to be generally well tolerated in clinical trials, with most adverse events being of mild to moderate severity 4, 6.
• Common adverse events include abdominal cramping, nausea, abdominal pain, and flatulence 3, 6, 7.
• Methylnaltrexone is contraindicated in patients with known or suspected mechanical intestinal stenosis, and patients receiving methylnaltrexone must be monitored 3.

Dosage and Administration

• Methylnaltrexone can be administered subcutaneously every other day, with doses ranging from 0.15 mg/kg to 0.30 mg/kg 4, 6.
• A dose of 12 mg/day has also been found to be effective in inducing laxation 5, 7.
• Weight-related dosing has been found to be effective, and the action of methylnaltrexone is dose dependent 3.