How should opioid‑induced constipation be managed in a patient taking chronic opioid analgesics?

Management of Opioid-Induced Constipation

All patients starting opioid analgesics should receive a prophylactic stimulant laxative (senna 2 tablets each morning or bisacodyl 5–15 mg daily) simultaneously with the first opioid dose, escalating systematically through osmotic laxatives if needed, and reserving peripherally acting μ-opioid receptor antagonists (PAMORAs) only for laxative-refractory cases. 1, 2

Prophylactic Strategy: Start on Day One

• Begin senna 2 tablets each morning (or bisacodyl 5–15 mg daily) with the very first opioid dose—never delay prophylaxis. 1, 2
• Up to 80–95% of patients develop opioid-induced constipation, and tolerance to this side effect never develops, making prophylaxis mandatory from day one. 1, 2
• Increase the laxative dose proportionally whenever the opioid dose is escalated to maintain bowel function. 1, 2
• Do not add docusate (stool softener) to senna—it provides no additional benefit and is less effective than senna alone. 1, 2
• Avoid supplemental fiber (psyllium, Metamucil) entirely, as bulk laxatives are ineffective for opioid-induced constipation and are not recommended. 1, 2
• Encourage adequate fluid intake and physical activity within patient limits (even bed-to-chair transfers) to support laxative effectiveness. 1, 2
• The treatment goal is one soft, non-forced bowel movement every 1–2 days without straining. 1, 2

Assessment Before Escalating Therapy

• Always rule out bowel obstruction or fecal impaction with abdominal examination and digital rectal exam before intensifying laxative therapy or adding PAMORAs—escalating stimulants or PAMORAs in the setting of obstruction risks perforation. 1, 2
• If digital rectal exam identifies a full rectum or fecal impaction, suppositories (bisacodyl or glycerin) or enemas are preferred first-line therapy before escalating oral laxatives. 1
• Enemas are contraindicated in patients with neutropenia, thrombocytopenia, paralytic ileus, recent colorectal or gynecological surgery, recent anal or rectal trauma, severe colitis, toxic megacolon, undiagnosed abdominal pain, or recent pelvic radiotherapy. 1

Second-Line Treatment: Escalate Stimulants and Add Osmotic Laxatives

• If constipation persists on standard senna dosing, increase bisacodyl to 10–15 mg two to three times daily. 1, 2
• Add an osmotic laxative when stimulant therapy alone is insufficient: 1, 2
  • Polyethylene glycol (PEG) 17 g in 8 oz water twice daily (preferred for elderly patients due to excellent safety profile), or 1, 2
  • Lactulose 30–60 mL daily, or 1, 2
  • Magnesium hydroxide or citrate 30–60 mL daily (use cautiously in renal impairment due to hypermagnesemia risk). 1, 2
• If gastroparesis is suspected, add metoclopramide 10–20 mg orally four times daily, but use caution in elderly patients due to tardive dyskinesia risk. 1, 2
• Rectal interventions (bisacodyl or glycerin suppositories) may be used if oral agents fail, but avoid in patients with thrombocytopenia or neutropenia. 1, 2

Third-Line Treatment: Peripherally Acting μ-Opioid Receptor Antagonists (PAMORAs)

Reserve PAMORAs only for patients with inadequate response to adequate trials of both stimulant and osmotic laxatives, and whose constipation is clearly attributable to opioid use. 1, 2

• Naldemedine 0.2 mg orally once daily has the strongest recommendation with high-quality evidence for laxative-refractory opioid-induced constipation. 1, 2
• Naloxegol 12.5–25 mg orally once daily is a strong recommendation with moderate-quality evidence. 1, 2
• 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 potential superiority. 1, 2, 3
• PAMORAs block peripheral opioid receptors in the gut without crossing the blood-brain barrier, thus preserving central analgesia. 2
• All PAMORAs are contraindicated in patients with known or suspected gastrointestinal obstruction due to perforation risk. 3
• Monitor for signs of opioid withdrawal (hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, rhinorrhea) especially in patients with compromised blood-brain barrier integrity. 3

Alternative Strategies for Refractory Cases

• Opioid rotation to fentanyl or methadone may reduce constipating effects when constipation remains refractory despite maximal laxative therapy. 1, 2
• Combined opioid/naloxone medications have been shown to reduce the risk of opioid-induced constipation through phase II and III studies. 1
• Lubiprostone 24 mcg orally twice daily (an intestinal secretagogue) may be considered, though evidence is more limited compared to PAMORAs. 1, 4

Objective Monitoring

• Use the Bowel Function Index to objectively evaluate severity (score ≥30 indicates clinically significant constipation) and monitor response to treatment. 2, 5, 6
• Regularly reassess bowel function and adjust the treatment regimen as needed throughout opioid therapy. 2

Critical Pitfalls to Avoid

• Never delay prophylactic laxatives—they must start with the first opioid dose, not after constipation develops. 1, 2
• Do not use stool softeners (docusate) alone without a stimulant laxative—they are ineffective for opioid-induced constipation. 1, 2
• Always exclude obstruction or impaction before escalating to higher stimulant doses or adding PAMORAs to prevent perforation. 1, 2
• Do not rely on dietary fiber as a preventive or therapeutic measure for opioid-induced constipation. 1, 2
• Avoid magnesium-based laxatives in patients with renal impairment due to hypermagnesemia risk. 1