What is the treatment for methadone-induced constipation?

Treatment for Methadone-Induced Constipation

For methadone-induced constipation, first-line treatment should include a stimulant laxative with or without a stool softener, or polyethylene glycol (PEG) with adequate fluid intake. 1 When these measures fail, peripherally acting mu-opioid receptor antagonists such as methylnaltrexone, naloxegol, or naldemedine should be used.

First-Line Management

Preventive Measures

• Stimulant laxatives: Use as prophylaxis (e.g., sennosides)
• Polyethylene glycol (PEG): 17g (heaping tablespoon) with 8 oz water twice daily
• Maintain adequate fluid intake
• Note: Docusate (stool softener) has not shown benefit and is not recommended 1
• Avoid supplemental medicinal fiber (e.g., psyllium) as it may worsen opioid-induced constipation 1

Initial Treatment When Constipation Develops

1. Assess for bowel obstruction
2. Titrate laxatives as needed
3. Goal: One non-forced bowel movement every 1-2 days
4. Consider adjuvant analgesics to reduce opioid dose

Second-Line Management for Persistent Constipation

If constipation persists despite first-line measures:

1. Re-assess for bowel obstruction and hypercalcemia
2. Review all medications that may cause constipation
3. Add or increase:
   • Stimulant laxatives (e.g., bisacodyl 10-15mg daily)
   • Magnesium-based products
   • Osmotic laxatives (sorbitol, lactulose, polyethylene glycol)
4. Consider opioid rotation to fentanyl (methadone rotation is not applicable as it's the causative agent)

Third-Line Management

For constipation refractory to above measures:

1. Peripherally acting mu-opioid receptor antagonists 1:

   • Methylnaltrexone (subcutaneous)
   • Naloxegol (oral)
   • Naldemedine (oral)

2. Other second-line agents:

   • Lubiprostone
   • Linaclotide

3. Consider enemas (sodium phosphate, saline, or tap water) to:

   • Dilate the bowel
   • Stimulate peristalsis
   • Lubricate stool

Important Considerations

• Enemas should be used sparingly due to risk of electrolyte abnormalities 1
• Avoid rectal suppositories or enemas in patients with neutropenia or thrombocytopenia 1
• Limit sodium phosphate laxatives/enemas to once daily in patients with renal dysfunction risk 1
• Peripherally acting mu-opioid receptor antagonists are contraindicated in mechanical bowel obstruction 1

Evidence for Methylnaltrexone in Methadone-Induced Constipation

A randomized controlled trial specifically examining methylnaltrexone for methadone-induced constipation showed:

• 100% laxation response in the treatment group vs. 0% in placebo group
• Significant reduction in oral-cecal transit time
• No opioid withdrawal symptoms or significant adverse effects 2

Special Note

While some case reports suggest that rotation from other opioids to methadone may reduce constipation 3, this is not applicable when methadone is already the causative agent of constipation.

The management of methadone-induced constipation remains undertreated despite effective options being available 4. Following this algorithmic approach should help achieve better bowel function and improved quality of life for patients on methadone therapy.