What is the recommended dosage of Relistor (methylnaltrexone) for opioid-induced constipation in patients with varying degrees of renal function, including those with severe impaired renal function?

Relistor (Methylnaltrexone) Dosing for Opioid-Induced Constipation

For patients with advanced illness and opioid-induced constipation who have failed laxative therapy, administer methylnaltrexone 0.15 mg/kg subcutaneously every other day, with dose adjustments required for severe renal impairment. 1

Standard Dosing by Patient Population

Advanced Illness/Palliative Care Patients

• Dose: 0.15 mg/kg subcutaneously every other day 1
• Maximum frequency: Once daily if needed 1
• This population includes cancer patients and others with life expectancy of 1 month or more 1
• Use only after inadequate response to conventional laxative therapy (senna, docusate, bisacodyl, polyethylene glycol, lactulose, etc.) 1, 2

Chronic Non-Cancer Pain Patients

• Dose: 12 mg subcutaneously once daily for patients weighing 38-114 kg 1, 3
• Alternative weight-based dosing: 0.15 mg/kg for patients outside this weight range 1
• Reserved for laxative-refractory cases 2

Dosing Adjustments for Renal Impairment

Critical adjustment required for severe renal dysfunction:

• Severe renal impairment (CrCl <30 mL/min): Reduce dose by 50% 3
  • For advanced illness: 0.075 mg/kg subcutaneously every other day
  • For chronic non-cancer pain: 6 mg subcutaneously once daily
• Mild to moderate renal impairment: No dose adjustment necessary 3
• End-stage renal disease: Use with extreme caution at reduced doses 3

Clinical Efficacy and Timing

Methylnaltrexone demonstrates rapid onset of action:

• 62.9% of patients achieve rescue-free bowel movements within 4 hours versus 9.6% with placebo 2, 4
• Median time to laxation: 0.8 hours with methylnaltrexone versus 23.6 hours with placebo 2, 4
• Approximately 50% experience laxation within 4 hours of first dose 2
• Response rates remain consistent throughout extended treatment 4, 5

Critical Pre-Treatment Requirements

Before initiating methylnaltrexone, you must:

• Rule out mechanical bowel obstruction or fecal impaction through clinical assessment 1, 2
• Confirm inadequate response to at least one trial of conventional laxatives 1, 2
• Verify stable opioid regimen for ≥2 weeks 1, 4
• Document <3 bowel movements in the previous week 1, 4

Absolute contraindication: Known or suspected mechanical gastrointestinal obstruction 2, 3

Administration Technique

• Route: Subcutaneous injection only 1, 3
• Frequency: Every other day as standard, may increase to once daily if needed 1, 3
• No maximum duration specified in guidelines 3

Common Pitfalls and Safety Considerations

Key adverse events to monitor:

• Abdominal pain and flatulence are most common 4, 5
• Diarrhea occurs more frequently than placebo 6
• Does NOT precipitate central opioid withdrawal or affect analgesia because methylnaltrexone is a quaternary amine with restricted blood-brain barrier penetration 4, 5
• No evidence of changes in pain scores during treatment 4

Why oral naltrexone is NOT appropriate:

• Oral naltrexone crosses the blood-brain barrier and would reverse central analgesia while precipitating acute opioid withdrawal 2
• Never substitute oral naltrexone for methylnaltrexone 2

Hierarchical Treatment Algorithm

Follow this stepwise approach:

1. First-line: Prophylactic stimulant laxatives (senna, docusate) with dose escalation as opioids increase 1
2. Second-line: Add osmotic laxatives (polyethylene glycol, lactulose, magnesium hydroxide) or additional stimulants (bisacodyl) 1
3. Third-line: Consider prokinetic agents (metoclopramide) if gastroparesis suspected 1
4. Fourth-line: Methylnaltrexone 0.15 mg/kg subcutaneously every other day for laxative-refractory cases 1, 2

Alternative Peripherally-Acting Agents

For chronic non-cancer pain with laxative-refractory OIC:

• Naldemedine receives the strongest recommendation (0.2 mg orally daily) with high-quality evidence 2
• Naloxegol is also strongly recommended (25 mg orally daily) with moderate-quality evidence 2
• These oral agents may be preferred over subcutaneous methylnaltrexone in ambulatory chronic pain patients 2

For advanced illness/palliative care:

• Methylnaltrexone remains the primary recommended peripherally-acting agent with conditional recommendation 2

Special Populations

• Geriatric patients: No specific dose adjustment required, but monitor closely for adverse effects 3
• Hepatic impairment: No dose adjustment necessary 3
• Critically ill patients: Limited data suggests efficacy (86% laxation within 24 hours), though not FDA-approved for this indication 7