What is the treatment for opioid-induced constipation?

Management of Opioid-Induced Constipation

For opioid-induced constipation, first-line treatment should be prophylactic stimulant laxatives (senna, bisacodyl) with or without stool softeners, followed by osmotic laxatives if needed, and peripherally acting μ-opioid receptor antagonists (PAMORAs) like naldemedine or naloxegol for laxative-refractory cases. 1, 2

First-Line Approach

Preventive Measures

• Initiate prophylactic laxative therapy when starting opioids - this is critical as constipation is the only opioid side effect that typically doesn't improve over time 2, 1
• Use stimulant laxatives (senna, bisacodyl) with stool softeners (docusate) as first-line prophylactic treatment 2, 1
• Standard starting dose: senna/docusate, 2 tablets every morning (maximum 8-12 tablets per day) 2
• Increase laxative dose proportionally when increasing opioid dose 2, 1
• Maintain adequate fluid intake and encourage physical activity if feasible 2, 1
• Ensure adequate dietary fiber intake, but avoid bulk-forming agents like Metamucil as they're unlikely to control opioid-induced constipation 2

When Constipation Develops

• Assess for cause and severity of constipation, ruling out bowel obstruction 2, 1
• Titrate stool softener/laxatives with goal of one non-forced bowel movement every 1-2 days 2
• Consider coanalgesic medications to allow reduction of opioid dose 2

Second-Line Approach (If Constipation Persists)

• Reassess for cause and severity of constipation; rule out bowel obstruction 2, 1
• Check for fecal impaction 2, 1
• Add osmotic laxatives such as:
  • Polyethylene glycol (PEG): one capful in 8 oz water daily 2
  • Lactulose: 30-60 mL daily 2
  • Magnesium hydroxide: 30-60 mL daily 2
  • Magnesium citrate 2
• Consider adding bisacodyl suppositories or Fleet enemas for acute relief 2
• Consider prokinetic agents (e.g., metoclopramide 10-20 mg PO three times daily) 2

Third-Line Approach (Laxative-Refractory OIC)

• For patients with inadequate response to traditional laxatives, PAMORAs are strongly recommended 2
• Naldemedine is strongly recommended over no treatment (high-quality evidence) 2, 1
• Naloxegol (25mg daily) is strongly recommended over no treatment (moderate-quality evidence) 2
  • Take on an empty stomach at least 1 hour before first meal of the day 3
  • Discontinue maintenance laxative therapy before starting naloxegol 3
  • For renal impairment (CrCl < 60 mL/min): start with 12.5 mg daily 3
• Methylnaltrexone (0.15 mg/kg subcutaneously) is conditionally recommended for advanced illness 2

Clinical Considerations and Pitfalls

• Failure to prophylactically start laxatives when initiating opioid therapy is a common mistake 1
• Avoid bulk-forming laxatives (psyllium/Metamucil) as first-line therapy for OIC 2, 1
• Always rule out bowel obstruction before aggressive laxative therapy 2, 1
• PAMORAs like naloxegol have shown significant improvement in spontaneous bowel movement frequency without reducing opioid analgesia 4
• Most adverse effects of PAMORAs are gastrointestinal and typically mild and transient 5, 6
• Patients receiving opioids for less than 4 weeks may be less responsive to naloxegol 3
• Avoid naloxegol in patients with known or suspected gastrointestinal obstruction 3
• Discontinue PAMORA treatment if the opioid pain medication is discontinued 3