What are the treatment options for opioid-induced constipation?

Treatment Options for Opioid-Induced Constipation

Traditional laxatives should be used as first-line agents for opioid-induced constipation (OIC), followed by peripherally acting μ-opioid receptor antagonists (PAMORAs) for laxative-refractory cases. 1

First-Line Treatment

Prophylactic Management

• Start prophylactic laxative therapy when initiating opioid treatment
• Recommended first-line options:
  • Stimulant laxatives with or without stool softeners 1
  • Polyethylene glycol (PEG) with 8 oz of water twice daily 1, 2
• Maintain adequate fluid intake 2

Active Management

1. Osmotic laxatives:

   • PEG is preferred due to excellent efficacy and safety profile 2
   • Alternatives: lactulose or magnesium salts (use caution with magnesium in renal impairment) 2

2. Stimulant laxatives:

   • Options: bisacodyl, senna, sodium picosulfate 1, 2
   • Mechanism: irritate sensory nerve endings to stimulate colonic motility 1
   • May cause abdominal cramping 2

3. Combination therapy:

   • Evidence suggests stimulant laxatives alone may be more effective than combined with stool softeners 1
   • One small study demonstrated that senna alone was as effective as senna-docusate combination 1

Important: Bulk-forming laxatives (psyllium, methylcellulose) are NOT recommended for OIC as they may worsen constipation 2

Second-Line Treatment (Laxative-Refractory OIC)

When to escalate: Consider second-line therapy if inadequate response to laxatives, defined as a Bowel Function Index score ≥30 1

Peripherally Acting μ-Opioid Receptor Antagonists (PAMORAs)

1. Naldemedine:

   • Strong recommendation with high-quality evidence 1
   • Blocks μ-opioid receptors in the gut without affecting central analgesia

2. Naloxegol:

   • Strong recommendation with moderate-quality evidence 1
   • FDA-approved for OIC in adult patients with chronic non-cancer pain 3
   • Monitor for abdominal pain and diarrhea; discontinue if severe symptoms occur 3

3. Methylnaltrexone:

   • Conditional recommendation with low-quality evidence 1
   • Administered subcutaneously as rescue therapy 1

Caution: PAMORAs are contraindicated in patients with known or suspected gastrointestinal obstruction 3

Monitoring and Assessment

• Assess the cause and severity of constipation to rule out obstruction 1
• Goal: achieve one non-forced bowel movement every 1-2 days 1
• Use the Bowel Function Index to objectively evaluate severity and monitor response 1, 4
• Reassess treatment efficacy within 2-4 weeks of initiating treatment 2

Common Pitfalls to Avoid

1. Failing to provide prophylactic treatment when initiating opioid therapy 2
2. Overreliance on stool softeners alone - docusate has not shown significant benefit 2
3. Using bulk-forming laxatives (psyllium) which may worsen OIC 1, 2
4. Delaying escalation to second-line therapy when first-line treatments fail 1
5. Not considering opioid rotation to fentanyl or methadone in persistent cases 1

Special Considerations

• For fecal impaction: consider glycerin suppositories or manual disimpaction before maintenance therapy 1, 2
• For persistent constipation: consider adding prokinetic agents such as metoclopramide 1
• Patients on methadone may experience higher frequency of gastrointestinal adverse reactions than those on other opioids 3
• PAMORAs should not be used in patients with gastrointestinal perforation risk or mechanical bowel obstruction 2, 3

Meta-analyses have shown that PAMORAs are effective for treating OIC with a number needed to treat of 5, but they may cause diarrhea, abdominal pain, nausea, or vomiting 5.