What is the role of Entereg (alvimopan) in managing postoperative ileus (POI) in patients undergoing colon surgery?

Entereg (Alvimopan) for Colon Surgery

Alvimopan 12 mg should be administered for patients undergoing colon resection surgery with primary anastomosis to accelerate gastrointestinal recovery and reduce hospital length of stay. 1

Indication and Patient Selection

Alvimopan is FDA-approved specifically for accelerating upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. 1 The drug works by selectively antagonizing peripheral μ-opioid receptors in the gastrointestinal tract without reversing central analgesic effects. 1

Key inclusion criteria:

• Patients ≥18 years undergoing bowel resection with primary anastomosis 1
• Patients receiving opioid-based analgesia postoperatively 1
• Surgery performed under general anesthesia 1

Absolute exclusions:

• Patients who received >3 doses of opioids in the 7 days prior to surgery 1
• Complete bowel obstruction 1
• Total colectomy, colostomy, or ileostomy procedures 1
• Intrathecal or epidural opioids/anesthetics (prohibited) 1

Dosing Protocol

The recommended regimen is alvimopan 12 mg:

• Initial dose: 30 minutes to 5 hours before scheduled surgery start, administered with a sip of water in fasting state 1, 2
• Subsequent doses: 12 mg twice daily beginning the first postoperative day 1
• Duration: Continue until hospital discharge or maximum 7 days (15 total doses) 1, 2
• Administration: Subsequent doses given without regard to meals 1

Clinical Efficacy

Alvimopan 12 mg demonstrates superior outcomes compared to the 6 mg dose:

• Accelerates time to GI recovery by 22 hours compared to placebo (HR=1.38, P<0.001) 3
• Reduces time to hospital discharge order written by 18 hours (mean 147 hours for placebo vs 129 hours for alvimopan 12 mg, P<0.001) 3
• The 12 mg dose provides more consistent benefits across both sexes and all ages 3
• Significantly reduces postoperative morbidity, prolonged hospital stay, and readmission rates (P<0.001) 3

In the pivotal FDA trials involving 2,154 patients undergoing bowel resection or radical cystectomy, alvimopan demonstrated clinically meaningful acceleration of GI recovery measured by time to tolerate solid food and first bowel movement. 1

Integration with Enhanced Recovery Protocols

Alvimopan should be incorporated into a comprehensive enhanced recovery after surgery (ERAS) approach that includes: 4, 5

Essential concurrent interventions:

• Mid-thoracic epidural analgesia for opioid-sparing pain control 4, 5
• Laparoscopic surgical approach when feasible 5
• Avoidance of routine nasogastric tube placement; early removal if placed 4, 5
• Optimized fluid management avoiding overload (weight gain <3 kg by postoperative day 3) 4
• Early mobilization starting the day after surgery 4
• Early oral intake with liquids offered the day following surgery 4
• Oral laxatives (bisacodyl 10 mg twice daily, magnesium oxide) once oral intake resumed 4, 5

Important Caveats and Safety Considerations

Critical safety restriction: Alvimopan is available only through the Entereg Access Support and Education (E.A.S.E.) program due to concerns from long-term studies showing associations with adverse cardiovascular outcomes, neoplasms, and fractures when used beyond short-term postoperative management. 2 The drug is restricted to short-term hospital use only (maximum 15 doses). 2

Common pitfall: Alvimopan efficacy is dependent on adequate opioid exposure. The drug works by antagonizing opioid effects on GI motility, so it is most effective when patients receive intravenous patient-controlled analgesia (PCA). 6 Post hoc analysis showed alvimopan was more effective in PCA groups than non-PCA groups. 6

Tolerability: Adverse event profiles are similar to placebo when used for ≤7 days postoperatively, and alvimopan does not compromise opioid-mediated analgesia. 3, 7, 2

When Alvimopan May Be Less Beneficial

The efficacy of alvimopan following total abdominal hysterectomy has not been established, and it should not be used for this indication. 1 Additionally, alvimopan has not been studied in other surgical populations beyond bowel resection and radical cystectomy. 2

For patients with opioid-induced constipation contributing to ileus, alternative agents like methylnaltrexone (0.15 mg/kg subcutaneously every other day) may be considered. 4

Pharmacokinetic Considerations

• Absolute bioavailability is only 6% (range 1-19%), with the drug acting primarily at peripheral GI receptors 1
• High-fat meals decrease absorption by 38% for Cmax and 21% for AUC, but the preoperative dose should be given fasting 1
• No dosage adjustment required for age, sex, race, or mild-to-moderate hepatic impairment 1
• Japanese patients show 2-fold increase in plasma concentrations but no dosage adjustment needed 1