What is the best treatment approach for opioid-induced constipation?

Management of Opioid-Induced Constipation

For opioid-induced constipation, a stepped approach beginning with polyethylene glycol (PEG) combined with a stimulant laxative as first-line therapy, followed by peripherally acting μ-opioid receptor antagonists (PAMORAs) for refractory cases, is the most effective treatment strategy.

First-Line Treatment

Preventive Measures

• Prophylactic laxative regimen should be initiated at the same time as opioid therapy 1:
  • Stool softener plus stimulant laxative (e.g., senna, docusate, 2 tablets every morning; maximum 8-12 tablets per day)
  • Increase laxative dose when increasing opioid dose
  • Maintain adequate fluid intake
  • Exercise if feasible

Initial Management

1. Polyethylene glycol (PEG) 17-34g daily 2

   • First-line pharmacological treatment with strong recommendation and moderate certainty of evidence
   • Increases complete spontaneous bowel movements by approximately 2.9 per week compared to placebo

2. Combine with stimulant laxative 1, 2

   • Bisacodyl 10-15mg daily for short-term use or rescue therapy
   • Senna 2-8 tablets daily

3. Important considerations:

   • Bulk-forming laxatives like psyllium are ineffective for opioid-induced constipation and should be avoided 2
   • Docusate alone is ineffective for constipation management 2
   • Goal: one non-forced bowel movement every 1-2 days 1

Second-Line Treatment (If Constipation Persists)

1. Reassess for cause and severity 1:

   • Rule out bowel obstruction
   • Check for impaction

2. Add additional agents 1:

   • Magnesium hydroxide 30-60 mL daily (avoid in renal impairment) 2
   • Lactulose 30-60 mL daily
   • Sorbitol 30 mL every 2 hours × 3 then as needed
   • Polyethylene glycol (increase dose if already using)
   • Consider prokinetic agent (e.g., metoclopramide 10-20 mg PO three times daily) 1

3. Consider enemas if needed 1:

   • Fleet, saline, or tap water enema
   • Contraindicated in neutropenia, thrombocytopenia, paralytic ileus, intestinal obstruction, recent colorectal surgery, severe colitis, or infection 2

Third-Line Treatment (Refractory Cases)

1. Peripherally acting μ-opioid receptor antagonists (PAMORAs) 2, 3:

   • Naloxegol 25 mg once daily orally (take on empty stomach) 3

     • Significantly higher response rates vs. placebo (39.7-44.4% vs. 29.3-29.4%) 4
     • Preserves central analgesic effects while blocking peripheral opioid effects 5
     • Contraindicated in patients with known or suspected GI obstruction 3

   • Methylnaltrexone 0.15 mg/kg subcutaneously every other day 1, 2

     • Consider when response to laxative therapy has been insufficient

2. Monitor for adverse effects 3, 4:

   • Most common: abdominal pain (21%), diarrhea (9%), nausea (8%)
   • Usually transient and mild 5
   • Discontinue if severe symptoms occur

Special Considerations

1. Risk factors requiring closer monitoring:

   • Patients on methadone have higher frequency of gastrointestinal adverse reactions than those on other opioids 3
   • Elderly patients are at higher risk for severe constipation and impaction 2

2. Contraindications for PAMORAs 3:

   • Known or suspected GI obstruction
   • Infiltrative GI tract malignancy
   • Recent GI tract surgery
   • Diverticular disease
   • Ischemic colitis

3. Red flags requiring urgent assessment 2:

   • Severe abdominal pain
   • No bowel movement for >3 days
   • Vomiting
   • Signs of bowel obstruction

Non-Pharmacological Approaches

• Maintain adequate fluid intake 1, 2
• Optimize toileting habits (attempt defecation twice daily, 30 minutes after meals) 2
• Maintain privacy and comfort during bowel movements 2
• Use proper positioning (a small footstool may help) 2

Remember that unlike other opioid side effects that improve over time, constipation typically persists throughout opioid therapy and requires ongoing management 1.