Gastrointestinal Opioid Antagonist


Gastrointestinal Opioid Antagonist, Peripheral Acting mu-opioid receptor antagonists, PAMORA, Methylnatrexone, Relistor, Movantik, Naloxegol, Symproic, Nalmedemedine, Alvimopan, Entereg

  • Indications
  1. Severe refractory Constipation due to Opioids
  • Mechanism
  1. Block Opioid binding in the intestinal tract
  2. Decreases mu-Opioid receptor mediated bowel paralysis
  • Preparations
  1. Movantik (Naloxegol) once daily orally in morning ($10/day)
    1. FDA approved for non-cancer, Opioid-Induced Constipation
    2. Requires Renal Dosing adjustment
    3. Chey (2014) N Engl J Med 370:2387-96 [PubMed]
  2. Methylnaltrexone (Relistor) injection ($70/day)
    1. Methylnaltrexone 5 mg or 0.15 mg/kg SQ
    2. Weight-based SQ Injection once or twice daily
    3. Diarrhea occurs in 8% and Abdominal Pain in 13%
    4. Requires Renal Dosing adjustment
    5. Contraindicated in Intestinal Obstruction
    6. Exercise caution in intestinal malignancy
  3. Symproic (Nalmedemedine)
    1. Dose: Once daily
    2. No renal dose adjustment needed
  4. Alvimopan (Entereg)
    1. Approved only for short-term management of post-operative ileus
    2. Restricted prescribing due to risk of Myocardial Infarction
  • Advantages
  1. Does not cross blood-brain barrier
  • Disadvantages
  1. All agents in this class are expensive as of 2017 (costs range between $10 to $70 per day)
  • Efficacy
  1. In general, results in one more Bowel Movement per week and may spare Laxative use
  2. Terminally ill patients
    1. Bowel Movement occurs within 4 hours of dose in 48% of patients (15% wiith Placebo)
    2. Median time to Bowel Movement is 45 minutes (>6 hours for Placebo)