What is the appropriate treatment for opioid‑induced constipation in a patient taking opioid analgesics?

Treatment of Opioid-Induced Constipation

Start a stimulant laxative (senna 2 tablets every morning or bisacodyl 5-15 mg daily) immediately when initiating opioid therapy, and escalate systematically through osmotic laxatives if needed, then to peripherally acting μ-opioid receptor antagonists (PAMORAs) for laxative-refractory cases. 1

Prophylactic Management (Start with Opioids)

All patients starting opioids require prophylactic laxatives because tolerance to constipation never develops and up to 80% will experience this side effect. 1

First-Line Prophylaxis

• Initiate senna 2 tablets every morning as the primary prophylactic agent simultaneously with the first opioid dose 2, 1
• Alternatively, use bisacodyl 5-15 mg daily if senna is not tolerated 1
• Do not add docusate (stool softener) to senna as it provides no additional benefit and stool softeners alone are ineffective 1
• Increase the laxative dose proportionally when increasing opioid doses to maintain bowel function 2, 1
• Ensure adequate fluid intake to support laxative effectiveness 2, 1
• Avoid supplemental fiber (psyllium, Metamucil) as it is ineffective for opioid-induced constipation and not recommended 2, 1

Treatment Goal

• Target one non-forced bowel movement every 1-2 days without straining 2, 1

Management of Persistent Constipation

Critical First Step

Always rule out bowel obstruction and check for fecal impaction before escalating laxative therapy 2, 1, 3

Second-Line Treatment

• Increase bisacodyl to 10-15 mg two to three times daily for persistent constipation 1, 3
• Add an osmotic laxative: polyethylene glycol (PEG) 17 grams in 8 oz water twice daily, lactulose 30-60 mL daily, or magnesium hydroxide 30-60 mL daily 2, 1
• Consider rectal interventions (bisacodyl suppository or glycerin suppository) if oral agents fail, but avoid in patients with thrombocytopenia or neutropenia 1, 3
• Add a prokinetic agent like metoclopramide 10-20 mg orally four times daily if gastroparesis is suspected, but use cautiously in elderly patients due to tardive dyskinesia risk 2, 1, 3

Laxative-Refractory Opioid-Induced Constipation

Third-Line: Peripherally Acting μ-Opioid Receptor Antagonists (PAMORAs)

For patients who fail adequate trials of laxatives, PAMORAs are highly effective and do not cross the blood-brain barrier, thus preserving central analgesic effects. 1

PAMORA Options (in order of recommendation strength):

• Naldemedine 0.2 mg orally once daily has the strongest recommendation with high-quality evidence 1, 4
• Naloxegol 12.5-25 mg orally once daily is a strong recommendation with moderate-quality evidence 1, 3
• Methylnaltrexone 0.15 mg/kg subcutaneously every other day (maximum dose per day) is a conditional recommendation with lower-quality evidence but may be superior in some network meta-analyses 2, 1, 3, 5

Alternative Strategies

• Opioid rotation to fentanyl or methadone may reduce constipating effects and should be considered for refractory cases 1, 3
• Lubiprostone 24 mcg twice daily can be used as an intestinal secretagogue, though evidence is more limited 1

Monitoring Response

• Use the Bowel Function Index to objectively assess severity and monitor treatment response; a score ≥30 indicates clinically significant constipation 1, 3, 6, 7
• Reassess bowel function regularly and adjust the treatment regimen as needed 1

Critical Pitfalls to Avoid

• Never delay prophylactic laxatives—they must be started simultaneously with the first opioid dose 1
• Do not use stool softeners (docusate) alone without a stimulant laxative; they are ineffective for opioid-induced constipation 1
• Always exclude bowel obstruction or impaction before adding or increasing stimulant laxatives or PAMORAs, as this may worsen outcomes 2, 1, 3
• Do not rely on dietary fiber as a preventive measure for opioid-induced constipation 2, 1
• Avoid sodium phosphate enemas in elderly patients; use isotonic saline enemas instead for better safety 3