What is the first line of treatment for opioid-induced constipation?

First-Line Treatment for Opioid-Induced Constipation

The first-line treatment for opioid-induced constipation is prophylactic administration of a stimulant laxative (senna or bisacodyl) combined with a stool softener (docusate), initiated at the time opioids are started, along with increased fluid intake and physical activity when feasible. 1

Prevention is Key

All patients starting opioid therapy should receive prophylactic laxatives unless they have pre-existing diarrhea. 1 This is critical because constipation is the only opioid side effect that does not improve over time. 1

Prophylactic Regimen

• Start senna plus docusate: 2 tablets every morning (maximum 8-12 tablets per day) 1
• Escalate laxative doses proportionally when increasing opioid doses 1
• Maintain adequate fluid intake 1
• Encourage dietary fiber only if patient has adequate fluid intake and physical activity 1
• Note: Bulk-forming agents like Metamucil or psyllium are NOT recommended for opioid-induced constipation and should be avoided 1
• Encourage exercise and mobility within patient's functional limits 1

When Constipation Develops Despite Prophylaxis

Initial Assessment (Critical Step)

• Rule out bowel obstruction through physical examination and consider abdominal X-ray 1
• Perform digital rectal examination to check for fecal impaction 1
• Assess for other treatable causes: hypercalcemia, hypokalemia, hypothyroidism, diabetes mellitus, and other constipating medications 1

First-Line Pharmacologic Treatment

Titrate stimulant laxatives (senna or bisacodyl) with or without stool softeners, targeting one non-forced bowel movement every 1-2 days. 1

• Bisacodyl: 10-15 mg orally daily to three times daily 1
• Senna: titrate up to maximum doses as needed 1
• Evidence shows that adding docusate (stool softener) to senna provides no additional benefit, though combination therapy remains commonly recommended 1

Alternative First-Line Options

Osmotic laxatives are equally acceptable as first-line agents: 1

• Polyethylene glycol (PEG): 1 capful in 8 oz water, can be given multiple times daily 1
• Lactulose: 30-60 mL daily to four times daily 1
• Magnesium hydroxide: 30-60 mL daily to twice daily 1
• Caution: Magnesium-containing laxatives can cause hypermagnesemia in renal impairment and should be used cautiously 1

Second-Line Treatment for Refractory Cases

If constipation persists despite adequate laxative therapy, consider peripherally-acting μ-opioid receptor antagonists (PAMORAs). 1

• Methylnaltrexone: 0.15 mg/kg subcutaneously every other day (maximum once daily) 1
• Naloxegol and naldemedine are also effective options 1, 2
• These agents are contraindicated in mechanical bowel obstruction and postoperative ileus 1
• Meta-analysis shows PAMORAs have a number needed to treat of 5, with relative risk of treatment failure 0.69 compared to placebo 2

Other Second-Line Options

• Lubiprostone (prostaglandin analog): effective for OIC in chronic pain patients 1, 2
• Linaclotide (guanylate cyclase-C agonist): can be considered 1
• Prucalopride: slightly better than placebo 2

Management of Fecal Impaction

If digital rectal examination reveals impaction: 1

• Glycerin suppository as initial intervention 1
• Manual disimpaction with pre-medication using analgesics ± anxiolytics 1
• Bisacodyl suppository: one rectally daily to twice daily 1
• Mineral oil retention enema 1
• Fleet, saline, or tap water enema until clear 1

Common Pitfalls to Avoid

• Never use bulk-forming laxatives (psyllium, Metamucil) as they are ineffective and potentially harmful in OIC 1
• Do not use enemas in patients with neutropenia, thrombocytopenia, recent pelvic surgery/radiotherapy, or severe colitis 1
• Always rule out obstruction before escalating laxative therapy 1
• Remember to increase laxative doses when opioid doses are increased 1
• Consider adding a prokinetic agent (metoclopramide 10-20 mg orally multiple times daily) if gastroparesis is suspected 1

Treatment Algorithm Summary

The evidence strongly supports a stepwise approach: 3, 4

1. Prevention with prophylactic stimulant laxatives at opioid initiation
2. Titration of first-line laxatives (stimulant or osmotic) to therapeutic effect
3. Addition of rectal interventions if impaction present
4. Escalation to PAMORAs if refractory to standard laxatives
5. Consider opioid rotation or dose reduction if all measures fail 1, 4