Description

Simple

A medication used to treat constipation caused by opioid or narcotic painkillers.

Clinical

A μ-opioid antagonist used for the treatment of opioid-induced constipation in palliative patients that are inadequately responding to laxative therapy.

Overview

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 in 2008.

Pharmacology

Indication

Treatment of opioids induced constipation in palliative patients that are inadequately responding to laxative therapy.

Pharmacodynamic

Use of opioids induces slowing of gastrointestinal motility and transit. Following remifentanil administration, the methylnaltrexone and placebo groups showed no change in pupiliary constriction while the naloxone group showed a marked change over the time interval tested.

Mechanism of action

Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract inhibit opioid-induced decrease in gastric motility and transit time. Because methylnaltrexone is a quaternary derivative of naltrexone, it produces its gastrointestinal effects without producing an... Read more

Absorption

Methylnaltrexone is rapidly absorbed.
Tmax (SubQ): 30 minutes (regardless of dose);
Cmax, 0.15 mg/kg SubQ dose = 117 ng/mL;
AUC24, 0.15 mg/kg SubQ dose = 175 ng·hr/mL;

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 half of the dose is excreted in the urine and somewhat less in feces.

Toxicity

LD50: 50 mg/kg (primates);
Orthostatic hypotension at plasma levels in excess of 1.400 ng/mL. The most common (>5%) adverse reactions reported with methylnaltrexone bromide are abdominal pain, flatulence, nausea, dizziness, diarrhea and hyperhidrosis.

Adverse Effects

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

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
Abacavir
Abacavir may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Acarbose
Acarbose may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Aceclofenac
Aceclofenac may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Acemetacin
Acemetacin may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Acetaminophen
Acetaminophen may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Acetazolamide
Acetazolamide may increase the excretion rate of Methylnaltrexone which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acid
Acetylsalicylic acid may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Aclidinium
Methylnaltrexone may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Acrivastine
Methylnaltrexone may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Acyclovir
Acyclovir may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Adefovir
Adefovir may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Adefovir dipivoxil
Adefovir dipivoxil may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Albutrepenonacog alfa
Methylnaltrexone may decrease the excretion rate of Albutrepenonacog alfa which could result in a higher serum level.
Alclofenac
Alclofenac may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Aldesleukin
Aldesleukin may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Alfentanil
The therapeutic efficacy of Alfentanil can be decreased when used in combination with Methylnaltrexone.
Allopurinol
Allopurinol may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Allylestrenol
Allylestrenol may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
Almasilate
Methylnaltrexone may decrease the excretion rate of Almasilate which could result in a higher serum level.
Alminoprofen
Alminoprofen may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level.
4 References
  1. 1 . Thomas J: Opioid-induced bowel dysfunction. J Pain Symptom Manage. 2008 Jan;35(1):103-13. Epub 2007 Nov 5.PubMed: 17981003
  2. 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. 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. 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