What is the best course of treatment for a 55-year-old man with worsening constipation symptoms, taking short-acting oxycodone (opioid) for lung cancer, with a history of ineffective over-the-counter fiber supplements and stimulant laxatives?

Management of Opioid-Induced Constipation in a Cancer Patient

This patient requires immediate escalation to a peripherally acting μ-opioid receptor antagonist (PAMORA), specifically naloxegol 25 mg once daily, since his constipation has failed first-line osmotic and stimulant laxatives. 1

Immediate Assessment Required

Before initiating treatment, perform a digital rectal examination to assess for fecal impaction, given the left lower quadrant firmness and hypoactive bowel sounds. 1 If the rectum is full or impaction is present, manual disimpaction with digital fragmentation and extraction is the first step. 1

Why Traditional Laxatives Have Failed

Fiber supplements (bulk laxatives like psyllium) are specifically contraindicated in opioid-induced constipation and should be discontinued immediately. 1 These agents can worsen constipation in patients with reduced GI motility and inadequate fluid intake, potentially causing mechanical obstruction. 1

The patient's current regimen of fiber supplements and stimulant laxatives represents an inappropriate combination for opioid-induced constipation, explaining the treatment failure. 1

Recommended Treatment Algorithm

Step 1: Address Potential Impaction

• Perform digital rectal examination now 1
• If impaction present: manual disimpaction followed by glycerin suppository or enema 1
• Ensure no contraindications to enemas (thrombocytopenia, neutropenia, recent pelvic radiation) 1

Step 2: Initiate PAMORA Therapy

Start naloxegol 25 mg orally once daily on an empty stomach (1 hour before or 2 hours after meals). 2, 3 This is the appropriate second-line therapy for laxative-refractory opioid-induced constipation. 1, 4

The evidence strongly supports naloxegol in this scenario:

• In patients with inadequate response to laxatives, 47-49% achieved response versus 29-31% with placebo 2
• Median time to first bowel movement was 6-12 hours versus 36-37 hours with placebo 2
• The drug antagonizes peripheral μ-opioid receptors in the GI tract without crossing the blood-brain barrier, preserving analgesia 3, 5

Step 3: Discontinue Inappropriate Medications

• Stop the fiber supplement immediately 1
• Continue or restart an osmotic laxative (polyethylene glycol 17g daily) as maintenance therapy alongside naloxegol 1
• The stimulant laxative can be discontinued once naloxegol is initiated 1

Critical Drug Interactions to Check

Before prescribing naloxegol, verify the patient is NOT taking:

• Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) - these are absolute contraindications 2
• Moderate CYP3A4 inhibitors require dose reduction to 12.5 mg daily 2
• Avoid grapefruit juice 2

Monitoring and Expected Response

• Target: at least 3 spontaneous bowel movements per week with improvement within 24 hours of first dose 2
• Monitor for abdominal pain (occurs in 21% of patients) and diarrhea (9%) - if severe, discontinue and consider restarting at 12.5 mg 2
• Watch for signs of opioid withdrawal (hyperhidrosis, chills, anxiety) - occurs in approximately 3% of patients 2
• Do not expect or wait for central analgesic effects to diminish - naloxegol does not reverse pain control 3, 5

Alternative PAMORA Options if Naloxegol Fails

If naloxegol is ineffective or not tolerated:

• Methylnaltrexone (subcutaneous) is an alternative PAMORA with similar efficacy 1
• Naldemedine (oral) is another option, though evidence is primarily from non-cancer populations 4, 6

Common Pitfall to Avoid

The most critical error in this case is continuing bulk-forming laxatives (fiber) in opioid-induced constipation. 1 This patient's worsening symptoms despite treatment likely reflect this inappropriate therapy choice, which can paradoxically worsen constipation and increase the risk of obstruction in patients with opioid-induced reduced GI motility. 1

Adjunctive Measures

While initiating naloxegol:

• Increase fluid intake if not contraindicated by other conditions 1
• Encourage mobility within the patient's functional limits 1
• Ensure privacy and proper positioning (footstool to assist with defecation) 1
• Consider abdominal massage 1