What is the best medication for opioid-induced constipation?

Best Medication for Opioid-Induced Constipation

Peripherally acting μ-opioid receptor antagonists (PAMORAs) are the most effective medications for treating opioid-induced constipation, with subcutaneous methylnaltrexone showing the highest efficacy among available options. 1

First-Line Approach

Before initiating specialized medications for opioid-induced constipation (OIC), standard laxative therapy should be attempted:

• Prophylactic treatment with stimulant laxatives (e.g., senna) with or without stool softeners should be started when initiating opioid therapy 1
• Increase laxative dose when increasing opioid dose 1
• Maintain adequate fluid intake and dietary fiber 1
• Encourage physical activity when feasible 1

When Standard Laxatives Fail

When response to standard laxative therapy is insufficient, PAMORAs should be considered:

PAMORAs Available for OIC:

1. Methylnaltrexone:

   • Available in both subcutaneous injection and oral tablet forms 1
   • FDA approved for OIC in both advanced illness/palliative care and chronic non-cancer pain 1
   • Shows predictable effectiveness with most patients achieving defecation within 90 minutes of subcutaneous administration 1
   • Unique advantage: not metabolized via CYP3A4, reducing drug-drug interactions 1
   • Dosing: 0.15 mg/kg subcutaneously every other day (no more than once daily) 1

2. Naloxegol:

   • Oral once-daily PAMORA (25 mg daily) 1, 2
   • FDA approved for OIC in adults with chronic non-cancer pain 2
   • Improves spontaneous bowel movement (SBM) response and frequency with moderate-quality evidence 1
   • More adverse effects than placebo, with 6 more treatment discontinuations per 100 patients 1

3. Naldemedine:

   • Oral once-daily PAMORA 1, 3
   • FDA approved for OIC in adults with chronic non-cancer pain 3
   • High-quality evidence supporting efficacy 1
   • Effective in both cancer and non-cancer pain populations 1

Comparative Efficacy

• A meta-analysis identified subcutaneous methylnaltrexone as more effective than oral preparations for rescue-free bowel movements 1
• PAMORAs as a class have a number needed to treat of 5 (95% CI, 4-7) 4
• All PAMORAs are more effective than placebo, with relative risk of failure to respond to therapy of 0.70 (95% CI, 0.64-0.75) 4

Special Considerations

• PAMORAs should not be used in patients with known or suspected mechanical bowel obstruction 1
• Patients with inadequate response to laxatives show improved response rates with PAMORAs 1
• Common side effects of PAMORAs include abdominal pain, diarrhea, nausea, and vomiting 4
• Pain scores and mean daily opioid doses typically remain stable with PAMORA use, indicating they don't interfere with pain control 1

Clinical Algorithm for OIC Management

1. Initial Management:

   • Start stimulant laxative (senna) with stool softener (docusate) prophylactically when initiating opioids 1
   • Titrate laxative dose with goal of one non-forced bowel movement every 1-2 days 1

2. If constipation persists:

   • Rule out bowel obstruction and other causes (hypercalcemia, hypokalemia) 1
   • Add osmotic laxatives (polyethylene glycol, lactulose, magnesium citrate) 1
   • Consider adding bisacodyl (oral or suppository) 1

3. For refractory OIC:

   • Initiate a PAMORA, with subcutaneous methylnaltrexone being the most effective option 1
   • For patients who prefer oral medication, naldemedine offers high-quality evidence of efficacy 1
   • Consider opioid rotation to fentanyl or methadone in selected cases 1

Pitfalls to Avoid

• Don't rely on fiber supplements like psyllium, which are ineffective and may worsen constipation 1
• Don't use docusate alone as it has not shown benefit 1
• Don't delay initiating PAMORAs when standard laxatives fail 1
• Don't use PAMORAs in patients with mechanical bowel obstruction 1
• Don't forget to maintain adequate fluid intake alongside laxative therapy 1