What is the best approach to manage opioid-induced constipation?

Management of Opioid-Induced Constipation

Prophylactic stimulant laxatives should be initiated when starting opioid therapy, with escalation to peripherally acting μ-opioid receptor antagonists (PAMORAs) for refractory cases. 1

Pathophysiology and Prevention

Opioid-induced constipation (OIC) occurs in approximately 40-80% of patients taking chronic opioid therapy 2. Unlike other opioid side effects, patients do not develop tolerance to constipation over time 3. Opioids cause constipation by:

• Slowing intestinal transit time
• Decreasing intestinal secretions
• Increasing anal sphincter tone 1

First-Line Management

Prophylactic Approach

• Stimulant laxatives: Start senna (2 tablets every morning; maximum 8-12 tablets per day) when initiating opioid therapy 3
• Increase laxative dose when increasing opioid dose 3
• Avoid bulk-forming laxatives like psyllium, as they are ineffective for OIC 3

Lifestyle Modifications

• Maintain adequate fluid intake
• Encourage physical activity as tolerated
• Establish regular toileting schedule, particularly after meals
• Use proper toileting position (elevate knees with footstool) 1

Treatment Algorithm for Established OIC

Step 1: Assessment

• Rule out bowel obstruction or impaction before aggressive treatment 3
• Assess for other causes of constipation (medications, metabolic disorders)
• Goal: One non-forced bowel movement every 1-2 days 3

Step 2: First-Line Pharmacological Treatment

• Stimulant laxatives: Senna or bisacodyl 10-15 mg, 2-3 times daily 3, 1
• Osmotic laxatives: Polyethylene glycol (PEG) 17g daily with 8 oz water 1

Step 3: For Persistent Constipation

• Add or switch to other laxatives:
  • Lactulose 15-30ml twice daily
  • Magnesium hydroxide or magnesium citrate (avoid in renal impairment)
  • Rectal bisacodyl once daily 3
• Consider adding prokinetic agent (metoclopramide 10-20 mg PO three times daily) 3

Step 4: Refractory OIC

• Peripherally acting μ-opioid receptor antagonists (PAMORAs):
  • Naldemedine: Strongly recommended over no treatment (high-quality evidence) 3
  • Naloxegol: Strongly recommended over no treatment (moderate-quality evidence) 3, 4
  • Methylnaltrexone: 0.15 mg/kg subcutaneously every other day (no more than once daily) 3, 5

Evidence for PAMORAs

• Methylnaltrexone: In a study of patients with advanced illness, 62% of patients receiving 0.15 mg/kg had rescue-free laxation within 4 hours compared to 14% with placebo 5
• Naloxegol: Response rate of 41.9% vs 29.4% for placebo in patients with chronic non-cancer pain 1
• PAMORAs overall: Meta-analysis showed relative risk of failure to respond to therapy of 0.70 (95% CI, 0.64-0.75) with number needed to treat of 5 6

Common Pitfalls to Avoid

1. Relying solely on stool softeners without stimulant laxatives 1
2. Inadequate prophylactic dosing of laxatives when starting opioids 1
3. Using bulk-forming laxatives like psyllium, which are ineffective for OIC 3
4. Delaying escalation to PAMORAs in refractory cases 1
5. Failing to rule out bowel obstruction before aggressive laxative therapy 1

Special Considerations

• Manual disimpaction may be necessary in some cases of severe impaction 3
• Consider opioid rotation to less constipating opioids (e.g., transdermal fentanyl) in persistent cases 1
• For patients with cancer pain, the management approach is similar but may require more aggressive intervention due to multiple contributing factors 3

By following this stepwise approach and anticipating constipation as an inevitable side effect of opioid therapy, clinicians can effectively manage OIC and improve patient quality of life.