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Gastrointestinal Opioid Antagonist

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Gastrointestinal Opioid Antagonist, Peripheral Acting Mu-Opioid Receptor Antagonist, PAMORA, Methylnaltrexone, Relistor, Movantik, Naloxegol, Symproic, Naldemedine, Alvimopan, Entereg

  • See Also
  1. Opioid Adverse Effect Management
  2. Bowel Regimen in Chronic Narcotic Use
  3. Amatiza (Lubiprostone)
  • 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. Naloxegol (Movantik) 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. Naldemedine (Symproic)
    1. Dose: Orally 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. Refractory Opioid Induced Constipation in Cancer and Palliative Care
    1. Both oral Naldemedine (Symproic) and SQ Methylnaltrexone (Relistor) are effective with benefits outweighing harms
    2. Brown (2023) Am Fam Physician 107(2):131-2 [PubMed]
  3. 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)
  • References
  1. (2017) Presc Lett 24(12): 70
  2. Portenoy (2008) J Pain Symptom Manage 35(5): 458-68 [PubMed]
  3. Thomas (2008) N Engl J Med 358(22): 2332-43 [PubMed]