What is the recommended treatment for a patient with opioid-induced ileus, particularly regarding the use of Reglan (metoclopramide)?

Reglan (Metoclopramide) for Opioid-Induced Ileus

Reglan (metoclopramide) is NOT recommended for opioid-induced ileus, as it lacks evidence of efficacy and carries significant risks, particularly tardive dyskinesia in elderly patients. 1, 2

Why Metoclopramide Should Not Be Used

• No proven efficacy: A systematic review by the Eastern Association for the Surgery of Trauma found that metoclopramide was not effective in expediting the resolution of ileus in adult surgical patients, with low-quality evidence. 1

• Historical data confirms ineffectiveness: A comprehensive 1999 review of prokinetic agents concluded that no literature supports reducing the duration of postoperative ileus with metoclopramide. 2

• Significant safety concerns: The National Comprehensive Cancer Network specifically warns about the risk of tardive dyskinesia when using metoclopramide, particularly in elderly patients, which should limit its use even when considered for gastroparesis in the context of opioid-induced constipation. 3, 4

Correct Management Approach for Opioid-Induced Bowel Dysfunction

First-Line Treatment: Traditional Laxatives

Start with stimulant laxatives immediately when opioids are initiated, as the American Gastroenterological Association strongly recommends laxatives as first-line agents for opioid-induced constipation. 3

• Senna 2 tablets every morning or bisacodyl 5-15 mg daily should be started prophylactically. 4
• Add osmotic laxatives (polyethylene glycol, lactulose, or magnesium citrate) if stimulant laxatives alone are insufficient. 3
• Goal: one non-forced bowel movement every 1-2 days. 3, 4

Before Escalating Therapy: Rule Out Complications

• Always exclude bowel obstruction and fecal impaction before intensifying treatment, as these require different management strategies. 3, 4
• Assess for other reversible causes: hypercalcemia, hypokalemia, hypothyroidism, and diabetes mellitus. 3, 4

Second-Line Treatment: Escalate Laxatives

• Increase bisacodyl to 10-15 mg two to three times daily for persistent constipation. 3, 4
• Add or increase osmotic laxatives such as polyethylene glycol or lactulose. 3
• Consider rectal interventions (bisacodyl or glycerin suppositories) if needed. 4

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

For laxative-refractory opioid-induced constipation, use PAMORAs instead of metoclopramide, as these agents have strong evidence for efficacy. 3

• Naldemedine 0.2 mg orally once daily has the strongest recommendation with high-quality evidence. 3, 4
• Naloxegol 12.5-25 mg orally once daily is strongly recommended with moderate-quality evidence. 3
• Methylnaltrexone 0.15 mg/kg subcutaneously every other day is conditionally recommended with lower-quality evidence. 3
• PAMORAs do not cross the blood-brain barrier and therefore do not interfere with central analgesic effects. 3, 4

Alternative Strategies

• Opioid rotation to fentanyl or methadone may be considered for refractory cases, as these opioids may have less constipating effects. 4
• Early enteral nutrition is strongly recommended in postoperative ileus to expedite resolution. 1

Critical Pitfalls to Avoid

• Do not use metoclopramide for opioid-induced ileus due to lack of efficacy and risk of tardive dyskinesia. 1, 2
• Never delay prophylactic laxatives when starting opioids—constipation is nearly universal and tolerance does not develop. 4
• Do not use stool softeners (docusate) alone—they are less effective than stimulant laxatives. 4
• Always rule out obstruction before adding stimulants or PAMORAs, as these can worsen mechanical obstruction. 4

Monitoring Response

• Use the Bowel Function Index to objectively assess severity and monitor treatment response, with a score ≥30 indicating clinically significant constipation requiring escalation. 3, 4