Methylnaltrexone


Description

Methylnaltrexone is a pheriphally-acting μ-opioid antagonist that acts on the gastrointestinal tract to decrease opioid-induced constipation without producing analgesic effects or withdrawal symptoms. It is also a weak CYP2D6 inhibitor. FDA approved...

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Pharmacology

Indication

Treatment of opioids induced constipation in palliative patients that are inadequately responding to... Read more

Pharmacodynamic

Use of opioids induces slowing of gastrointestinal motility and transit. Following remifentanil admi... Read more

Mechanism of action

Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal trac... Read more

Absorption

Methylnaltrexone is rapidly absorbed.
Tmax (SubQ): 30 minutes (regardless of dose);
Cmax, 0.15 mg...
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Protein binding

11% to 15% bound to human plasma proteins.

Volume of distribution

Volume of distribution, steady state = 1.1 L/kg

Clearance

10.5 ± 1.5 ml/min/kg (IV)

Half life

terminal: 8.89 ± 2.59 h (intravenous)
terminal: 6.14- 8.83 h (subcutaneous)

Route of elimination

Most of the drug is eliminated as unchanged drug (85% of administered radioactivity). Approximately... Read more

Toxicity

LD50: 50 mg/kg (primates);
Orthostatic hypotension at plasma levels in excess of 1.400 ng/mL. The...
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Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Abdominal Pain US
  • adult
  • Kind: experimental
    • Percent: 29%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Abdominal Pain US
    • adult
  • Kind: experimental
    • Percent: 21%
  • Kind: placebo
    • Percent: 7%
  • Clinical Trial
    Abdominal Pain US
    • adult
  • Kind: experimental
    • Percent: 14%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Flatulence US
    • adult
  • Kind: experimental
    • Percent: 13%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Nausea US
    • adult
  • Kind: experimental
    • Percent: 12%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Nausea US
    • adult
  • Kind: experimental
    • Percent: 9%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Dizziness US
    • adult
  • Kind: experimental
    • Percent: 7%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Diarrhea US
    • adult
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Diarrhea US
    • adult
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Hyperhidrosis US
    • adult
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Diarrhea US
    • adult
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Abdominal distension US
    • adult
  • Kind: experimental
    • Percent: 4%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Headache US
    • adult
  • Kind: experimental
    • Percent: 4%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Hot flush US
    • adult
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Hyperhidrosis US
    • adult
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Vomiting US
    • adult
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Chills US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Rhinorrhea US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Muscle Spasms US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Anxiety US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Tremor US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Kind: placebo
    • Percent: <1%
  • Clinical Trial
    Chills US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Malaise US
    Post Marketing
    Pain US
    Post Marketing
    Opioid Withdrawal US
    Post Marketing
    Gastrointestinal Perforation US
    Post Marketing
    Vomiting US
    Post Marketing
    Gastrointestinal cramping US
    Post Marketing
    Flushing US
    Post Marketing
    Diaphoresis US
    Post Marketing

    Contraindications

    • Regions: US
    • Patient Conditions:
        • Name: Recurrent obstruction
        • Drugbank Id: DBCOND0108482
        • Modification Of:
          • Condition Status: recurrent
          • Base:
            • Name: Obstruction
            • Drugbank Id: DBCOND0012263
    • Hypersensitivity:
      • false
    • Regions: US
    • Regions: US
    • Patient Conditions:
        • Name: Gastrointestinal obstruction
        • Drugbank Id: DBCOND0010786
    • Regions: US
    • Patient Conditions:
        • Name: Suspected gastrointestinal obstruction
        • Drugbank Id: DBCOND0107630

    Food Interactions

      Information currently not available.

    Interactions

    Type in a drug name to check for interaction with Methylnaltrexone

    Abacavir may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Acarbose may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Aceclofenac may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Acemetacin may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Acetaminophen may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Acetazolamide may increase the excretion rate of Methylnaltrexone which could result in a lower serum level and potentially a reduction in efficacy.
    Acetylsalicylic acid may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Methylnaltrexone may decrease the excretion rate of Aclidinium which could result in a higher serum level.
    Methylnaltrexone may decrease the excretion rate of Acrivastine which could result in a higher serum level.
    Acyclovir may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Adefovir may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Adefovir dipivoxil may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Methylnaltrexone may decrease the excretion rate of Albutrepenonacog alfa which could result in a higher serum level.
    Alclofenac may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Aldesleukin may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    The therapeutic efficacy of Alfentanil can be decreased when used in combination with Methylnaltrexone.
    Allopurinol may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Allylestrenol may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
    Methylnaltrexone may decrease the excretion rate of Almasilate which could result in a higher serum level.
    Alminoprofen may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.

    References

    • 1 . Thomas J: Opioid-induced bowel dysfunction. J Pain Symptom Manage. 2008 Jan;35(1):103-13. Epub 2007 Nov 5. [PubMed: 17981003]
    • 2 . Rotshteyn Y, Boyd TA, Yuan CS: Methylnaltrexone bromide: research update of pharmacokinetics following parenteral administration. Expert Opin Drug Metab Toxicol. 2011 Feb;7(2):227-35. doi: 10.1517/17425255.2011.549824. Epub 2011 Jan 11. [PubMed: 21222554]
    • 3 . Chandrasekaran A, Tong Z, Li H, Erve JC, DeMaio W, Goljer I, McConnell O, Rotshteyn Y, Hultin T, Talaat R, Scatina J: Metabolism of intravenous methylnaltrexone in mice, rats, dogs, and humans. Drug Metab Dispos. 2010 Apr;38(4):606-16. doi: 10.1124/dmd.109.031179. Epub 2010 Jan 6. [PubMed: 20053817]
    • 4 . Bader S, Jaroslawski K, Blum HE, Becker G: Opioid-induced constipation in advanced illness: safety and efficacy of methylnaltrexone bromide. Clin Med Insights Oncol. 2011;5:201-11. doi: 10.4137/CMO.S4867. Epub 2011 Jul 14. [PubMed: 21836816]

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