What is the recommended treatment for opioid-induced constipation with Relistor (methylnaltrexone) in patients with advanced illness?

Methylnaltrexone (Relistor) for Opioid-Induced Constipation in Advanced Illness

Subcutaneous methylnaltrexone is the recommended treatment for opioid-induced constipation in patients with advanced illness when response to standard laxative therapy has been insufficient, with a dosage of 0.15 mg/kg administered subcutaneously every other day. 1, 2, 3

Mechanism and Efficacy

Methylnaltrexone is a peripheral μ-opioid receptor antagonist that:

• Does not cross the blood-brain barrier
• Selectively antagonizes opioid receptors in the gastrointestinal tract
• Preserves centrally mediated analgesic effects of opioids 1, 2

Clinical evidence demonstrates:

• Rapid onset of action with most patients achieving defecation within 90 minutes of administration 1, 2
• Approximately 45-60% of patients experience rescue-free bowel movements within 4 hours after the first dose 4, 5
• Sustained efficacy with continued use over 3 months 5

Dosing Protocol for Advanced Illness

Weight-Based Dosing

• Less than 38 kg: 0.15 mg/kg
• 38 kg to less than 62 kg: 8 mg (0.4 mL)
• 62 kg to 114 kg: 12 mg (0.6 mL)
• More than 114 kg: 0.15 mg/kg 3

Administration Schedule

• Initially once every other day
• Do not administer more frequently than once per 24-hour period
• May increase to once daily if needed 1, 2, 3

Renal Impairment Adjustment

For moderate to severe renal impairment (CrCl <60 mL/min):

• Reduce dose by 50% (0.075 mg/kg)
• 38 kg to <62 kg: 4 mg
• 62 kg to 114 kg: 6 mg 3

Treatment Algorithm

1. First-line approach: Implement preventive measures for all patients on opioids

   • Prophylactic stimulant laxative (senna) with stool softener (docusate)
   • Adequate fluid intake
   • Maintain physical activity as tolerated 1, 2

2. When constipation develops despite preventive measures:

   • Rule out bowel obstruction (contraindication for methylnaltrexone)
   • Check for impaction
   • Titrate laxatives with goal of one non-forced bowel movement every 1-2 days 1

3. When response to laxative therapy is insufficient:

   • Initiate subcutaneous methylnaltrexone at appropriate weight-based dose
   • Administer every other day as needed
   • Patient should be within close proximity to toilet facilities after administration 1, 3

4. Monitor response:

   • Assess for laxation within 4 hours
   • If inadequate response, consider increasing frequency to once daily
   • Continue to monitor for adverse effects 2, 5

Clinical Considerations

Efficacy Markers

• Median time to laxation among responders: approximately 45 minutes (range 0-4 hours) 5
• Higher baseline opioid doses and fewer laxations in the preceding week may predict better response to methylnaltrexone 6

Adverse Effects

• Most common: abdominal pain, nausea, diarrhea, and hyperhidrosis
• Generally mild to moderate in severity
• No significant impact on pain control or opioid withdrawal symptoms 1, 2, 5

Contraindications

• Known or suspected mechanical gastrointestinal obstruction 2, 3

Quality of Life Impact

Methylnaltrexone treatment is associated with:

• Significant improvement in constipation-specific quality of life 7
• Reduced distress related to constipation 1, 2
• Improved patient satisfaction with bowel function 6

Important Caveats

1. Discontinue methylnaltrexone if treatment with opioid pain medication is discontinued 3

2. Fiber supplements like psyllium (Metamucil) are unlikely to control opioid-induced constipation and may worsen symptoms 1, 2

3. Re-evaluate the need for methylnaltrexone when the opioid regimen changes to avoid adverse reactions 3

4. Methylnaltrexone is specifically approved for OIC in advanced illness and palliative care patients whose response to conventional laxative therapy has been insufficient 1, 2, 3