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

Management of Opioid-Induced Constipation

Traditional laxatives should be used as first-line therapy for opioid-induced constipation, with peripherally acting μ-opioid receptor antagonists (PAMORAs) reserved for laxative-refractory cases. 1

First-Line Management

Preventive Measures

• Start prophylactic laxatives when initiating opioid therapy:
  • Stimulant laxative (e.g., senna, 2 tablets every morning; maximum 8-12 tablets per day) with or without stool softener 1
  • Alternatively, polyethylene glycol (PEG) with 8 oz water twice daily 1
• Increase laxative dose when increasing opioid dose 1
• Maintain adequate fluid intake and physical activity 1, 2
• Dietary fiber intake is recommended, but supplemental fiber products like Metamucil are ineffective for OIC and not recommended 1

When Constipation Develops

1. Assess for cause and severity of constipation
2. Rule out bowel obstruction
3. Titrate stool softener/laxatives with goal of one non-forced bowel movement every 1-2 days 1

Second-Line Management (Persistent Constipation)

If constipation persists despite first-line therapy:

1. Reassess for cause and rule out bowel obstruction
2. Check for impaction
3. Consider adding:
   • Osmotic laxatives: magnesium hydroxide (30-60 mL daily), lactulose (30-60 mL daily), sorbitol, or polyethylene glycol 1
   • Additional stimulants: bisacodyl (2-3 tablets PO daily or suppository) 1
   • Enemas: Fleet, saline, or tap water 1
   • Prokinetic agent: metoclopramide (10-20 mg PO three times daily) 1

Third-Line Management (Laxative-Refractory OIC)

For patients with laxative-refractory OIC, PAMORAs are recommended:

1. Naldemedine: Strongly recommended over no treatment (high-quality evidence) 1
2. Naloxegol: Strongly recommended over no treatment (moderate-quality evidence) 1
   • Dosage: 25 mg orally once daily on an empty stomach 3, 1
   • Response rate: 41.9% vs 29.4% for placebo 1
   • Particularly effective in patients with inadequate response to laxatives 1, 4
3. Methylnaltrexone: Conditionally recommended over no treatment (low-quality evidence) 1
   • Dosage: 0.15 mg/kg subcutaneously every other day 1, 5
   • For chronic non-cancer pain: 12 mg subcutaneously once daily 5

Efficacy Comparison

• PAMORAs have a number needed to treat (NNT) of 5 for OIC 6
• Naloxegol 25 mg showed significant improvement in:
  • Spontaneous bowel movement (SBM) response rate
  • Change in SBM frequency
  • Reduction in straining severity
  • Improved stool consistency 1
• Methylnaltrexone showed 59% response rate vs 38% for placebo in chronic non-cancer pain 5

Adverse Effects

• Naloxegol: Primarily gastrointestinal (abdominal pain, diarrhea, nausea) 1, 7
  • 9.4% discontinuation rate due to adverse events vs 4.2% for placebo 1
• Methylnaltrexone: Generally well-tolerated with similar adverse effect profile 5
• PAMORAs do not affect central analgesia or induce opioid withdrawal when used as directed 8, 4

Special Considerations

• Consider opioid rotation to fentanyl or methadone if constipation persists 1
• PAMORAs work by antagonizing peripheral μ-opioid receptors in the GI tract without crossing the blood-brain barrier, thus not interfering with pain control 8
• For patients with renal impairment, naloxegol dose should be reduced to 12.5 mg daily in moderate-to-severe cases 8
• Pain scores and daily opioid doses typically remain stable with PAMORA therapy 1, 4

Common Pitfalls to Avoid

• Relying solely on stool softeners without stimulant laxatives 2
• Inadequate prophylactic laxative dosing when initiating or increasing opioid therapy 1
• Using bulk-forming laxatives like psyllium, which are ineffective for OIC 1
• Delaying escalation to PAMORAs in truly laxative-refractory cases 1
• Failing to rule out bowel obstruction before aggressive laxative therapy 1