What are the treatment options for opioid-induced constipation?

Treatment of Opioid-Induced Constipation

Start all patients on prophylactic stimulant laxatives (senna or bisacodyl) with or without stool softeners at the initiation of opioid therapy, and escalate systematically through osmotic laxatives, then peripherally acting μ-opioid receptor antagonists (PAMORAs) for laxative-refractory cases. 1, 2

Prophylactic Treatment (Start with Opioids)

• Initiate a stimulant laxative immediately when starting opioids since tolerance to constipation does not develop and it is nearly universal. 1, 2
• Use senna 2 tablets every morning or bisacodyl 10-15 mg daily as first-line prophylaxis. 2
• Adding a stool softener like docusate to stimulant laxatives is actually less effective than stimulant laxatives alone, so use stimulants with or without softeners, not softeners alone. 1
• Alternatively, use polyethylene glycol (PEG) 17g in 8 oz water twice daily. 1, 2
• Increase laxative doses when increasing opioid doses to maintain bowel function. 2
• Avoid supplemental fiber (psyllium) as it is ineffective for opioid-induced constipation. 1

First-Line Treatment (When Constipation Develops)

• Rule out bowel obstruction or fecal impaction before escalating therapy through physical exam and consider abdominal x-ray if indicated. 1, 2
• Target one non-forced bowel movement every 1-2 days. 1, 2
• Titrate stimulant laxatives upward: increase bisacodyl to 10-15 mg two to three times daily or senna to 2 tablets twice daily. 2, 3
• Add osmotic laxatives if stimulants alone are insufficient: PEG, lactulose, or magnesium-based products (avoid magnesium in renal impairment). 1, 2, 3
• Maintain adequate fluid intake as a supportive measure. 1, 2

Second-Line Treatment (Persistent Constipation)

• Reassess to rule out obstruction or impaction before further escalation. 1
• Add rectal interventions: bisacodyl suppository 10 mg, glycerin suppository, or enemas (fleet, saline, or tap water). 1, 2, 3
• Consider adding a prokinetic agent like metoclopramide 10-20 mg four times daily, though chronic use carries risk of tardive dyskinesia. 1, 2
• Consider opioid rotation to fentanyl or methadone as these may cause less constipation. 1, 2
• Assess for other contributing causes: hypercalcemia, hypokalemia, hypothyroidism, diabetes, or other constipating medications. 2

Third-Line Treatment (Laxative-Refractory OIC)

For patients with inadequate response to laxatives (Bowel Function Index ≥30), escalate to peripherally acting μ-opioid receptor antagonists. 1, 2

PAMORA Selection (in order of recommendation strength):

• Naldemedine: Strongest recommendation with high-quality evidence for laxative-refractory OIC. 1
• Naloxegol 12.5-25 mg once daily: Strong recommendation with moderate-quality evidence; FDA-approved for chronic non-cancer pain. 1, 4
• Methylnaltrexone 0.15 mg/kg subcutaneously every other day: Conditional recommendation with lower-quality evidence; useful as rescue therapy when constipation is clearly opioid-related. 1, 2

Important PAMORA Considerations:

• PAMORAs do not cross the blood-brain barrier and thus do not interfere with central analgesic effects. 1
• These agents are significantly more expensive than traditional laxatives but highly effective when laxatives fail. 1, 5
• Meta-analysis shows PAMORAs reduce failure to respond by 30% compared to placebo (RR 0.70), with number needed to treat of 5. 5
• Common side effects include diarrhea, abdominal pain, nausea, and vomiting. 5

Alternative Agents (Limited Evidence)

• Lubiprostone: No formal recommendation due to evidence gaps, though some data suggests modest benefit. 1, 5
• Prucalopride (5-HT4 agonist): No formal recommendation for OIC due to insufficient evidence, though licensed for chronic constipation in women. 1
• Linaclotide: May have some role but lacks strong evidence specifically for OIC. 1

Monitoring Response

• Use the Bowel Function Index (validated 3-question tool) to objectively assess severity and monitor treatment response. 1, 2, 6
• A score ≥30 indicates clinically significant constipation requiring escalation beyond first-line laxatives. 1
• Regularly reassess bowel function and adjust treatment as needed. 2

Critical Pitfalls to Avoid

• Never delay prophylactic laxatives when starting opioids—constipation is inevitable and tolerance does not develop. 1
• Do not use stool softeners alone as they are less effective than stimulant laxatives. 1
• Always rule out obstruction before escalating therapy, especially before adding stimulants or PAMORAs. 1, 2
• Avoid bulk-forming laxatives (fiber supplements) in opioid-induced constipation as they are ineffective and may worsen symptoms. 1
• Do not use metoclopramide chronically without considering tardive dyskinesia risk, especially in elderly patients. 1, 2