What are the contraindications for Entereg (alvimopan)?

Contraindications for Entereg (Alvimopan)

Entereg (alvimopan) is contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking alvimopan. 1

Mechanism and Indication

Alvimopan is a peripherally acting mu-opioid receptor antagonist (PAMORA) that is FDA-approved specifically for the in-hospital management of postoperative ileus following bowel resection surgery. It works by:

• Binding to GI tract μ-opioid receptors
• Antagonizing opioid effects on GI motility and secretion
• Having restricted ability to cross the blood-brain barrier, thus not affecting opioid analgesia 2

Detailed Contraindications

1. Prior opioid use: Patients who have received therapeutic doses of opioids for more than 7 consecutive days immediately before starting alvimopan 1

2. Restricted use setting: Alvimopan should be held preoperatively according to perioperative management guidelines 2

3. Off-label use restrictions: While alvimopan has been studied for opioid-induced constipation (OIC) in chronic non-cancer pain, it is not FDA-approved for this indication, and the doses used in clinical trials for OIC are not currently commercially available 2

Important Safety Considerations

Alvimopan has a restricted distribution program (Entereg Access Support and Education program) due to safety concerns observed in long-term studies, including:

• Adverse cardiovascular outcomes
• Increased risk of neoplasms
• Increased risk of fractures 3

Administration Limitations

• Maximum treatment duration: 7 days (15 total doses maximum)
• Hospital-only administration: Cannot be dispensed for outpatient use
• Dosing schedule: 12 mg administered 30 minutes to 5 hours before surgery, followed by 12 mg twice daily beginning the day after surgery 3

Clinical Efficacy Context

Despite these contraindications, alvimopan has demonstrated significant benefits in appropriate patients:

• Accelerates GI recovery after bowel resection by approximately 15-22 hours compared to placebo 4
• Reduces hospital length of stay by approximately one day 5
• Significantly improves time to first bowel movement (HR 1.27,95% CI 1.12 to 1.43) 2
• Improves time to first toleration of solid food (HR 1.22,95% CI 1.11 to 1.34) 2

Clinical Pearls

• Alvimopan does not interfere with the analgesic properties of mu-opioid agonists when used as directed 2
• The drug is specifically designed for short-term use in the hospital setting only
• When considering peripherally acting mu-opioid receptor antagonists for chronic opioid-induced constipation, other FDA-approved options like methylnaltrexone, naloxegol, or naldemedine should be considered instead 2

Remember that alvimopan's safety profile is favorable for short-term use but has significant concerns with extended use, which is why it has a restricted access program and specific contraindications.