What is the role of Entereg (alvimopan) in Enhanced Recovery After Surgery (ERAS) protocols?

Role of Alvimopan in Enhanced Recovery After Surgery (ERAS) Protocols

Alvimopan should be included in ERAS protocols for patients undergoing bowel resection and radical cystectomy to accelerate gastrointestinal recovery and reduce hospital length of stay. 1, 2

Mechanism and Indication

Alvimopan (Entereg) is a peripherally acting μ-opioid receptor antagonist that:

• Is FDA-approved to accelerate upper and lower gastrointestinal recovery following surgeries that include partial bowel resection with primary anastomosis 2
• Does not cross the blood-brain barrier, thus preventing antagonism of central opioid receptors while blocking peripheral opioid receptors in the GI tract 1
• Counteracts the negative effects of opioid analgesics on bowel function without interfering with pain control

Clinical Benefits in ERAS Protocols

When incorporated into ERAS protocols, alvimopan provides several significant benefits:

1. Accelerated GI Recovery:

   • Reduces time to first toleration of clear liquids (HR 1.34,95% CI 1.19-1.51, p<0.001) 1
   • Reduces time to first toleration of solid food (HR 1.22,95% CI 1.11-1.34, p<0.001) 1
   • Reduces time to first bowel movement (HR 1.27,95% CI 1.12-1.43, p<0.001) 1

2. Reduced Hospital Stay:

   • Decreases length of stay (HR 1.17,95% CI 1.10-1.25, p<0.001) 1
   • In radical cystectomy patients, reduces mean hospital stay from 6.9 to 5.7 days (p=0.01) 3

3. Economic Benefits:

   • Reduces hospitalization costs despite the medication expense 1
   • Provides cost savings through shorter hospital stays and fewer complications

Specific Surgical Applications

Colorectal Surgery

• Recommended in ERAS Society guidelines for colonic surgery 1
• Accelerates GI recovery when used with postoperative opioid analgesia in open colonic resection 1

Radical Cystectomy

• Significantly accelerates recovery of GI function and reduces length of stay 1
• Reduces mean time to regular diet (5.3 vs 4.1 days, p<0.01) 3

Dosing and Administration

• Dosage: 12 mg administered 30 minutes to 5 hours prior to surgery, followed by 12 mg twice daily beginning the day after surgery 2
• Duration: Continue until discharge for a maximum of 7 days (not to exceed 15 doses) 2
• Administration: Can be taken with or without food 2

Important Considerations and Limitations

Safety Considerations

• REMS Program: Available only through a restricted program due to potential risk of myocardial infarction with long-term use 2
• Contraindication: Contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking alvimopan 2

Integration with Other ERAS Components

For optimal results, alvimopan should be used alongside other ERAS components:

• Mid-thoracic epidural analgesia when appropriate 1
• Laparoscopic approach when feasible 1
• Avoidance of fluid overload 1, 4
• Avoidance of nasogastric decompression 1
• Early mobilization 4
• Appropriate fluid management targeting neutral fluid balance after initial resuscitation 4

Practical Implementation

1. Patient Selection:

   • Most beneficial for patients undergoing open bowel resection or radical cystectomy
   • Consider for patients at high risk for postoperative ileus
   • Verify no recent prolonged opioid use (>7 days)

2. Timing:

   • Administer first dose preoperatively (30 minutes to 5 hours before surgery)
   • Continue postoperatively until discharge or maximum of 7 days

3. Monitoring:

   • Assess for signs of GI recovery (bowel sounds, flatus, bowel movements)
   • Monitor for potential adverse effects
   • Track time to oral intake tolerance and hospital discharge readiness

Conclusion

Alvimopan is a valuable component of ERAS protocols, particularly for patients undergoing open bowel resection and radical cystectomy. Its inclusion in these protocols significantly accelerates GI recovery, reduces hospital length of stay, and may decrease overall healthcare costs.