What is the best medication for long-term management of constipation in an adult patient with opioid use disorder?

Best Medication for Long-Term Management of Opioid-Induced Constipation

For adults with opioid use disorder experiencing constipation, start immediately with a stimulant laxative (senna or bisacodyl) as prophylaxis, and if this fails after adequate trial, escalate to naldemedine as the preferred peripherally acting μ-opioid receptor antagonist (PAMORA) based on the highest quality evidence. 1, 2

Immediate Prophylaxis: Start at Opioid Initiation

Begin a stimulant laxative prophylactically when opioids are started—do not wait for constipation to develop. 1, 2

• Senna 2 tablets every morning or bisacodyl 5-15 mg daily are first-line options 2
• Patients do not develop tolerance to opioid-induced constipation, making prophylaxis essential in nearly all cases 1
• Alternative: Polyethylene glycol (PEG) 17 grams in 8 oz water twice daily 1, 3
• Avoid docusate (stool softeners alone): Evidence shows adding docusate to senna is actually less effective than senna alone 1, 2
• Avoid supplemental fiber (psyllium): This is ineffective and may worsen opioid-induced constipation 1, 2

Critical First Step

Always rule out bowel obstruction or fecal impaction before initiating or escalating treatment. 1, 2

Goal of Treatment

Target one non-forced bowel movement every 1-2 days 1, 2

Escalation for Persistent Constipation

If constipation persists despite stimulant laxatives:

Second-Line: Increase Laxatives

• Increase bisacodyl to 10-15 mg two to three times daily 2
• Add osmotic laxatives: PEG, lactulose, or magnesium-based products 1, 2
• Consider rectal interventions (bisacodyl or glycerin suppositories) if needed 2
• Reassess for obstruction, hypercalcemia, and other constipating medications 1

Third-Line: PAMORAs for Laxative-Refractory Cases

When adequate trials of laxatives fail, escalate to peripherally acting μ-opioid receptor antagonists. 1

Naldemedine 0.2 mg orally once daily is the strongest recommendation with high-quality evidence and was found to be the most effective PAMORA in network meta-analysis 1, 2

Alternative PAMORAs include:

• Naloxegol 12.5-25 mg once daily (moderate-quality evidence, FDA-approved for chronic non-cancer pain) 1, 2
• Methylnaltrexone 0.15 mg/kg subcutaneously every other day (lower-quality evidence, FDA-approved for advanced illness/palliative care) 1, 2

Key advantage of PAMORAs: They do not cross the blood-brain barrier and therefore do not interfere with central analgesic effects or precipitate withdrawal 2

Fourth-Line: Alternative Agents

If PAMORAs are unavailable or ineffective:

• Lubiprostone 24 mcg twice daily (FDA-approved for opioid-induced constipation in chronic non-cancer pain, but limited evidence quality) 1, 4
• Prucalopride (selective 5-HT4 agonist, low-quality evidence) 1
• Opioid rotation to fentanyl or methadone may reduce constipation 1, 2

Important Limitations and Caveats

Effectiveness of lubiprostone in patients taking methadone has not been established, which is particularly relevant for opioid use disorder patients 4

PAMORAs should not be used in patients with known or suspected mechanical bowel obstruction 1

Avoid rectal interventions in patients with neutropenia or thrombocytopenia 1

Sodium phosphate-containing products should be limited in patients with renal dysfunction 1

Monitoring Response

Use the Bowel Function Index to objectively assess severity and monitor treatment response, with scores ≥30 indicating clinically significant constipation 2, 5, 6

Regular reassessment of bowel function and treatment adjustment is essential 2

Common Pitfalls to Avoid

Never delay prophylactic laxatives when starting opioids—constipation is nearly universal and tolerance does not develop 1, 2, 7

Do not use stool softeners (docusate) alone—they are ineffective 1, 2

Always rule out obstruction before escalating therapy, especially before adding stimulants or PAMORAs 1, 2

Do not add supplemental fiber, as it worsens opioid-induced constipation 1, 2