Treatment of Opioid-Induced Constipation
For opioid-induced constipation, first-line treatment should be traditional laxatives, with peripherally acting μ-opioid receptor antagonists (PAMORAs) such as naldemedine, naloxegol, or methylnaltrexone recommended for laxative-refractory cases. 1
First-Line Management
- Prophylactic laxative therapy should be initiated when opioids are prescribed to prevent constipation 1
- Stimulant laxatives (senna, bisacodyl) with or without stool softeners are recommended as first-line prophylactic treatment 1
- Increase laxative dose when increasing opioid dose to maintain efficacy 1
- Goal of therapy: one non-forced bowel movement every 1-2 days 1
- Osmotic laxatives (polyethylene glycol, lactulose, magnesium citrate) are effective alternatives or additions to stimulant laxatives 1
- Bulk-forming laxatives like psyllium or Metamucil are NOT recommended for opioid-induced constipation 1, 2
Non-Pharmacological Measures
- Maintain adequate fluid intake and dietary fiber when possible 1
- Encourage physical activity if feasible for the patient 1
- Optimize toileting habits, including attempting defecation 30 minutes after meals 2
- Ensure privacy and comfort for normal defecation 2
Management of Persistent Constipation
Step 1: Assessment
- Rule out bowel obstruction before escalating treatment 1
- Check for impaction if constipation persists 1
- Assess for other causes of constipation (medications, hypercalcemia) 1
Step 2: Escalation of Laxative Therapy
- Add or increase stimulant laxatives (bisacodyl, senna) 1
- Consider adding osmotic laxatives (magnesium hydroxide, lactulose, polyethylene glycol) 1
- Consider adding a prokinetic agent (metoclopramide) if gastroparesis is suspected 1
Step 3: For Laxative-Refractory OIC
- PAMORAs are recommended for patients who have inadequate response to traditional laxatives 1
- Naldemedine is strongly recommended over no treatment (high-quality evidence) 1
- Naloxegol is strongly recommended over no treatment (moderate-quality evidence) 1, 3
- Methylnaltrexone is conditionally recommended over no treatment (low-quality evidence) 1
- These agents block μ-opioid receptors in the gut without affecting central analgesic effects 4, 5
Evidence for PAMORAs
- Naloxegol (25 mg daily) demonstrated significantly higher response rates compared to placebo (39.7-44.4% vs. 29.3-29.4%) 6
- Naloxegol does not reduce opioid-mediated analgesia while effectively treating constipation 6
- Methylnaltrexone shows predictable effectiveness after subcutaneous administration, with most patients achieving defecation within 90 minutes 1
- A meta-analysis of μ-opioid receptor antagonists showed an overall number needed to treat of 5 for OIC 7
Special Considerations
- Reduce naloxegol dose (12.5 mg daily) in patients with renal impairment 4, 8
- Most common side effects of PAMORAs are gastrointestinal (abdominal pain, diarrhea, nausea) 6, 7
- Lubiprostone (8 mcg twice daily) is FDA-approved for OIC in adult patients with chronic non-cancer pain 9
- PAMORAs should not be used in patients with known or suspected mechanical gastrointestinal obstruction 9
Common Pitfalls
- Failure to prophylactically start laxatives when initiating opioid therapy 1
- Using bulk-forming laxatives as first-line therapy for OIC 1, 2
- Not escalating laxative dose when increasing opioid dose 1
- Not ruling out bowel obstruction before aggressive laxative therapy 1
- Magnesium-based laxatives should be used cautiously in patients with renal impairment 2