II. Indications

  1. Opioid Induced Constipation
  2. Opioid Induced Constipation refractory to Laxatives, in patients with advanced illness

III. Contraindications

  1. Contraindicated in Intestinal Obstruction
  2. Exercise caution in intestinal malignancy

IV. 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

V. 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%

VI. 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

VII. 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

VIII. 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

IX. 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]

X. Drug Interactions

  1. Avoid with other opioid Antagonists
  2. Stop other Laxatives while taking Methylnaltrexone (may restart as needed in 3 days)

XII. 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]

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

relistor (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
RELISTOR 12 MG/0.6 ML SYRINGE $232.20 per ml
RELISTOR 12 MG/0.6 ML VIAL $230.56 per ml
RELISTOR 150 MG TABLET $23.17 each

Ontology: methylnaltrexone (C0066411)

Definition (NCI_NCI-GLOSS) The active ingredient in a drug used to relieve certain side effects caused by treatment with opiods (pain killers similar to morphine), such as constipation (hard, dry stools), itching, and low urine flow. Methylnaltrexone binds to opioid receptors outside the brain and may block the side effects of opioid drugs without affecting their ability to relieve pain. Methylnaltrexone is a type of peripheral opioid receptor antagonist.
Definition (NCI) A methyl derivative of noroxymorphone with selective, opioid-receptor antagonistic activity. Methylnaltrexone displaces opioids from peripheral opioid receptors in the gastrointestinal tract, the bladder, and the skin, resulting in decreases in opioid-related constipation, urinary retention, and pruritis, respectively. Methylnaltrexone does not cross the blood-brain barrier and does not affect the centrally-mediated analgesic effect of opioids.
Definition (PDQ) A methyl derivative of noroxymorphone with selective, opioid-receptor antagonistic activity. Methylnaltrexone displaces opioids from peripheral opioid receptors in the gastrointestinal tract, the bladder, and the skin, resulting in decreases in opioid-related constipation, urinary retention, and pruritis, respectively. Methylnaltrexone does not cross the blood-brain barrier and does not affect the centrally-mediated analgesic effect of opioids. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=437863&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=437863&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48403" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C032257
SnomedCT 431072004, 429838001
English 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphinanium-6-one, methylnaltrexone, quaternary ammonium naltrexone, 17-(Cyclopropylmethyl)-4,5alpha-epoxy-3,14-dihydroxy-17-methyl-6-oxomorphinanium, Quaternary Ammonium Naltrexone, MNTX, N-methylnaltrexone bromide, Methylnaltrexone (substance), Methylnaltrexone, Methylnaltrexone (product), methylnaltrexone [Chemical/Ingredient], METHYLNALTREXONE
Spanish metilnaltrexona, metilnaltrexona (producto), metilnaltrexona (sustancia)

Ontology: Relistor (C2343585)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C032257
English Relistor