Relistor (Methylnaltrexone) vs Oral Naltrexone for Opioid-Induced Constipation
Relistor (methylnaltrexone) is the appropriate choice for opioid-induced constipation unresponsive to laxatives, while oral naltrexone should not be used for this indication. Oral naltrexone is a centrally-acting opioid antagonist that will reverse analgesia and precipitate opioid withdrawal—it has no role in treating opioid-induced constipation 1, 2.
Why Methylnaltrexone (Relistor) is the Correct Agent
Methylnaltrexone is a peripherally-acting μ-opioid receptor antagonist (PAMORA) that blocks opioid receptors in the gastrointestinal tract without crossing the blood-brain barrier, thereby reversing constipation while preserving pain control 1, 2, 3.
Guideline-Based Recommendations
The treatment algorithm for opioid-induced constipation follows a stepwise approach:
- First-line therapy: Traditional laxatives (stimulant laxatives with or without stool softeners, or polyethylene glycol) 1
- Second-line therapy for laxative-refractory cases: Peripherally-acting μ-opioid receptor antagonists 1
For patients with advanced illness receiving palliative care who have inadequate response to laxatives, the American Gastroenterological Association suggests methylnaltrexone (conditional recommendation, low-quality evidence), while giving stronger recommendations to naldemedine and naloxegol for chronic non-cancer pain 1.
The American Society of Clinical Oncology specifically recommends methylnaltrexone for cancer patients with opioid-induced constipation who have had inadequate response to conventional laxative therapy 2.
Clinical Efficacy Data
The evidence supporting methylnaltrexone is compelling:
- 62.9% of patients with advanced illness achieved rescue-free bowel movements with methylnaltrexone versus only 9.6% with placebo 2
- Median time to laxation was 0.8 hours (48 minutes) with methylnaltrexone compared to 23.6 hours with placebo 2, 4
- Approximately 50% of patients experience laxation within 4 hours of the first dose, compared to only 15% with placebo 2
- Treatment does not impact analgesic response or precipitate opioid withdrawal 2, 4, 3
Dosing and Administration
Methylnaltrexone is administered subcutaneously at 0.15 mg/kg every other day, with the option to increase to once daily if needed 1, 2. Most patients achieve defecation within 90 minutes of administration 2.
Why Oral Naltrexone is Contraindicated
Oral naltrexone is a non-selective, centrally-acting opioid antagonist that crosses the blood-brain barrier. Using it would:
- Reverse central opioid analgesia, causing uncontrolled pain 1, 2
- Precipitate acute opioid withdrawal symptoms 1, 2
- Provide no therapeutic benefit for constipation management 1
The critical distinction is that methylnaltrexone's quaternary ammonium structure prevents blood-brain barrier penetration, while naltrexone freely crosses into the central nervous system 1, 3.
Important Clinical Considerations
Before initiating methylnaltrexone therapy:
- Rule out mechanical bowel obstruction or impaction through clinical assessment 1, 2
- Methylnaltrexone is contraindicated in known or suspected mechanical gastrointestinal obstruction 1, 2, 5
- Ensure patients have failed adequate trials of traditional laxatives first 1
Common Adverse Effects
The most frequent side effects are mild to moderate and include:
One critical caveat: A 2020 ICU study found increased mortality with methylnaltrexone in critically ill mechanically ventilated patients (10 deaths vs 2 with placebo, p=0.007), though this population differs substantially from typical palliative care or chronic pain patients 6. This finding suggests caution in the ICU setting specifically.
Alternative PAMORAs
If methylnaltrexone is unavailable or unsuitable: