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Methylnaltrexone

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Methylnaltrexone, Relistor

  • See Also
  1. Gastrointestinal Opioid Antagonist
  2. Opioid Adverse Effect Management
  3. Bowel Regimen in Chronic Narcotic Use
  4. Amatiza (Lubiprostone)
  • Indications
  1. Opioid Induced Constipation
  2. Opioid Induced Constipation refractory to Laxatives, in patients with advanced illness
  • Contraindications
  1. Contraindicated in Intestinal Obstruction
  2. Exercise caution in intestinal malignancy
  • Mechanism
  1. Quaternary derivative of Naltrexone
  2. Blocks Opioid binding in the intestinal tract
  3. Decreases mu-Opioid receptor mediated bowel paralysis
  4. Also decreases Opioid induced Pruritus
  5. Does not cross the blood brain barrier
    1. Does not affect Opioid related analgesia
  • Dosing
  • Adults
  1. General
    1. Stay near a toilet for 4 hours after dose
    2. Give injection while seated or lying down
    3. Protect medication from light
  2. Opioid Induced Constipation
    1. Subcutaneous (SQ: 12 mg SQ once daily
      1. Renal Dose (GFR <60 ml/min): 6 mg/day SQ
    2. Oral: 450 mg once daily in the morning
      1. Renal Dose (GFR <60 ml/min): 150 mg/day SQ
      2. Take on an empty Stomach (at least 30 minutes before first meal)
  3. Opioid Induced Constipation refractory to Laxatives, in patients with advanced illness
    1. Weight <38 kg: 0.15 mg/kg SQ every other day
    2. Weight 38 to 61 kg: 8 mg SQ every other day
    3. Weight 62 to 114 kg: 12 mg SQ every other day
    4. Weight >115 kg: 0.15 mg SQ every other day
    5. GFR <60 ml/min: Decrease SQ dose 50%
  • Adverse Effects
  1. Diarrhea (3 to 8%)
  2. Abdominal Pain (4 to 13%)
  3. Hyperhidrosis (2%)
  4. Headache (1%)
  5. Vomiting (1%)
  6. Opioid Withdrawal (uncommon)
    1. Chills, anxiety or Yawning
  • Safety
  1. Contraindicated in Lactation
  2. Pregnancy Category B
    1. No affect on organogenesis in animal studies, but has not been studied in human pregnancy
  • Pharmacokinetics
  1. Rapid onset of action: 2 hours
  2. Peak serum levels: 0.5 hours SQ or IV, or 3 hours for tablets (1.5 hours if Fasting)
  3. Elimination Half-Life: 15 hours
  4. Hepatic metabolism
    1. Liver conjugation via sulfotransferase and aldo-keto reductase
    2. Metabolites include Methylnaltrexone sulfate and methyl-6-naltrexol
  5. Renal excretion
    1. Most Methylnaltrexone is excreted unchanged in the urine
  • Efficacy
  1. In general, results in one more Bowel Movement per week and may spare Laxative use
  2. Best efficacy in those on Opioids for >4 weeks
  3. Consider stopping medication if no effect after 4 doses
  4. 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]
  • Drug Interactions
  1. Avoid with other opioid Antagonists
  2. Stop other Laxatives while taking Methylnaltrexone (may restart as needed in 3 days)
  • Resources
  1. Methylnaltrexone (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c488fb7c-0a5b-487c-b452-996809d1cb99
  • References
  1. (2023) Management of Constipation, Presc Lett, #390108
  2. (2017) Presc Lett 24(12): 70
  3. Hoopes and LoVecchio (2023) Crit Dec Emerg Med 37(11): 32
  4. Portenoy (2008) J Pain Symptom Manage 35(5): 458-68 [PubMed]
  5. Thomas (2008) N Engl J Med 358(22): 2332-43 [PubMed]