How should I manage opioid‑induced constipation while maintaining adequate analgesia?

Management of Opioid-Induced Constipation

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

Initial Assessment and Prophylaxis

Begin prophylactic treatment simultaneously with the first opioid dose—do not wait for constipation to develop, as up to 95% of patients will experience this side effect and tolerance never develops. 1, 2

First-Line Prophylactic Regimen

• Senna 2 tablets every morning is the primary recommended prophylactic agent 1, 3
• Bisacodyl 5-15 mg daily is an acceptable alternative stimulant laxative 1, 3
• Do NOT add docusate (stool softener) to senna—adding docusate provides no additional benefit and is less effective than stimulant laxatives alone 4, 3
• Avoid supplemental fiber (psyllium, Metamucil)—fiber is ineffective for opioid-induced constipation and may worsen symptoms 1, 4, 3
• Increase the laxative dose proportionally whenever the opioid dose is escalated 1, 3
• Ensure adequate fluid intake to support laxative effectiveness 1
• Encourage physical activity when appropriate 1

Treatment Goal

• Achieve one soft, non-forced bowel movement every 1-2 days without straining 1, 4, 3

Second-Line Treatment for Persistent Constipation

Before escalating therapy, always rule out bowel obstruction or fecal impaction with abdominal examination and consider digital rectal exam if constipation is suspected. 1, 4, 3

Escalation Strategy

• Increase bisacodyl to 10-15 mg two to three times daily if constipation persists on standard dosing 1, 4, 3
• Add an osmotic laxative when stimulant therapy alone is insufficient: 1, 3
  • Polyethylene glycol (PEG) 17 grams in 8 oz water twice daily, or
  • Lactulose 30-60 mL daily, or
  • Magnesium hydroxide or citrate 30-60 mL daily
• Consider rectal interventions (bisacodyl or glycerin suppository) if oral agents fail, but avoid in patients with thrombocytopenia or neutropenia 1, 4
• If gastroparesis is suspected, add metoclopramide 10-20 mg orally four times daily, but use with caution in elderly patients due to risk of tardive dyskinesia 1, 3

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

For laxative-refractory opioid-induced constipation in patients with chronic non-cancer pain, escalate to PAMORAs, which block peripheral opioid receptors in the gut without crossing the blood-brain barrier or affecting central analgesia. 1, 3

PAMORA Selection (in order of recommendation strength)

1. Naldemedine 0.2 mg orally once daily—strongest recommendation with high-quality evidence 3
2. Naloxegol 12.5-25 mg orally once daily—strong recommendation with moderate-quality evidence 3, 5
   • Contraindicated with strong CYP3A4 inhibitors (clarithromycin, ketoconazole) 5
   • Reduce dose to 12.5 mg daily with moderate CYP3A4 inhibitors (diltiazem, erythromycin, verapamil) 5
   • Avoid grapefruit or grapefruit juice 5
   • Take on empty stomach at least 1 hour before or 2 hours after meals 5
   • Discontinue maintenance laxatives before starting; may resume after 3 days if symptoms persist 5
3. Methylnaltrexone 0.15 mg/kg subcutaneously every other day (maximum once daily)—conditional recommendation with lower-quality evidence 1, 3, 6
   • Some network meta-analyses suggest potential superiority over other PAMORAs 3
   • Monitor for severe or persistent diarrhea; discontinue if this develops 6

PAMORA Safety Considerations

• All PAMORAs are contraindicated in patients with known or suspected gastrointestinal obstruction due to risk of perforation 5, 6
• Monitor for symptoms of opioid withdrawal (hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, yawning), especially in patients with disruptions to the blood-brain barrier 6
• Discontinue if severe, persistent, or worsening abdominal pain develops 6
• PAMORAs do not interfere with central analgesic effects 3

Alternative Strategies for Refractory Cases

• Opioid rotation to fentanyl or methadone may reduce constipating effects 1, 3
• Lubiprostone 24 mcg twice daily (chloride channel activator) can be considered, though evidence is limited 3

Objective Monitoring

• Use the Bowel Function Index to objectively assess severity and monitor treatment response 3, 7
• A score of 30 or higher indicates clinically significant constipation 3
• Regular reassessment of bowel function and adjustment of the treatment regimen is essential 3

Critical Pitfalls to Avoid

• Never delay prophylactic laxatives—they must be started simultaneously with the first opioid dose 4, 3
• Do not use stool softeners alone without a stimulant laxative—they are ineffective for opioid-induced constipation 4, 3
• Always exclude bowel obstruction before adding or increasing stimulant laxatives or PAMORAs, as this can precipitate perforation 1, 4, 3, 5, 6
• Do not rely on dietary fiber as a preventive or treatment measure 1, 4, 3
• Patients receiving opioids for less than 4 weeks may be less responsive to PAMORAs 5
• Discontinue PAMORAs if opioid therapy is discontinued 5