What is the recommended laxative regimen for a patient who develops constipation due to morphine therapy?

Management of Morphine-Induced Constipation

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

Prophylactic Regimen (Start with First Morphine Dose)

• Begin senna 2 tablets every morning as the primary prophylactic agent simultaneously with the first morphine dose 2, 1
• Bisacodyl 5-15 mg daily is an acceptable alternative stimulant laxative 1
• Polyethylene glycol (PEG) 17 grams in 8 oz water twice daily can be used as an alternative or addition to stimulant laxatives 2, 1
• Do not add docusate (stool softener) to senna—it provides no additional benefit and is actually less effective than senna alone 2, 1
• Increase the laxative dose proportionally whenever the morphine dose is escalated 1
• Maintain adequate fluid intake throughout treatment 2, 1
• Avoid supplemental fiber (psyllium, Metamucil) as it is ineffective for opioid-induced constipation 2, 1

Rationale: Up to 80-95% of patients on morphine develop constipation, and tolerance to this adverse effect never develops, making prophylaxis essential from day one 2, 1, 3

Treatment Goal: Achieve one soft, non-forced bowel movement every 1-2 days without straining 2, 1

Assessment Before Escalating Therapy

• Always rule out bowel obstruction or fecal impaction with abdominal examination before intensifying laxative therapy 2, 1
• Assess for other reversible causes: hypercalcemia, hypokalemia, hypothyroidism, diabetes mellitus 1
• Discontinue any non-essential constipating medications 1

Critical Pitfall: Adding stimulant laxatives or PAMORAs in the presence of bowel obstruction can cause perforation 1

Second-Line Treatment (Persistent Constipation Despite Prophylaxis)

• Increase bisacodyl to 10-15 mg two to three times daily 2, 1
• Add an osmotic laxative:
  • Polyethylene glycol (PEG) 17 grams in 8 oz water twice daily, or 2, 1
  • Lactulose 30-60 mL daily, or 2, 1
  • Magnesium hydroxide or citrate 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
• Add metoclopramide 10-20 mg orally four times daily if gastroparesis is suspected, but use caution in elderly patients due to tardive dyskinesia risk 2, 1

Third-Line Treatment (Laxative-Refractory Opioid-Induced Constipation)

PAMORAs block peripheral opioid receptors in the gut without crossing the blood-brain barrier, preserving central analgesia 1

• Naldemedine 0.2 mg orally once daily has the strongest recommendation with high-quality evidence 1
• Naloxegol 12.5-25 mg orally once daily is a strong recommendation with moderate-quality evidence 1
• Methylnaltrexone 0.15 mg/kg subcutaneously every other day (maximum once daily) is a conditional recommendation with lower-quality evidence, though some network meta-analyses suggest superiority 2, 1

When to Use PAMORAs: Reserve for patients with inadequate response to adequate trials of stimulant and osmotic laxatives, when constipation is clearly attributable to opioid use 2, 1

Alternative Strategies for Refractory Cases

• Consider opioid rotation to fentanyl or methadone, which may have less constipating effects 2, 1
• Lubiprostone 24 mcg twice daily can be used as an intestinal secretagogue, though evidence is limited 1

Monitoring Response

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

Common Pitfalls to Avoid

• Never delay prophylactic laxatives—they must start with the first morphine dose 1
• Do not use stool softeners (docusate) alone without a stimulant laxative—they are ineffective 2, 1
• Always exclude obstruction before escalating to higher doses of stimulant laxatives or adding PAMORAs 2, 1
• Do not rely on dietary fiber as a preventive measure for morphine-induced constipation 2, 1
• PAMORAs are contraindicated in patients with known or suspected gastrointestinal obstruction due to perforation risk 1