Skip to main content
SpringerLink
Log in

Methylnaltrexone

  • Adis Drug Profile
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Methylnaltrexone is a selective μ-opioid receptor antagonist that has restricted ability to cross the blood-brain barrier, thus enabling reversal of opioid-induced peripheral effects, such as constipation, without affecting the central effects, such as pain relief.

Treatment with subcutaneous methylnaltrexone 0.15–0.30 mg/kg, relative to placebo, significantly increased the rescue-free laxation response rate within 4 hours of the first dose (primary endpoint) in adult patients with opioid-induced constipation and advanced illness in two randomized, double-blind, placebo-controlled, multicentre, phase III studies; one was a single-dose study (n=154), the other a multiple-dose study (n= 133).

In the multiple-dose study, rescue-free laxation response rates within 4 hours after at least two of the first four doses (coprimary endpoint) were also significantly higher in methylnaltrexone recipients than in placebo recipients.

Moreover, median time to laxation after the first dose was significantly shorter in methylnaltrexone recipients than in placebo recipients in both studies.

Methylnaltrexone was not associated with any significant changes in pain scores or central opioid withdrawal in these studies.

Methylnaltrexone was generally well tolerated in clinical trials; most adverse events were of mild to moderate severity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1

Similar content being viewed by others

References

  1. Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs 2003; 63(7): 649–71

    Article  PubMed  CAS  Google Scholar 

  2. Yuan CS. Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects. Ann Pharmacother 2007 Jun; 41(6): 984–93

    Article  PubMed  CAS  Google Scholar 

  3. Becker G, Galandi D, Blum HE. Peripherally acting opioid antagonists in the treatment of opiate-related constipation: a systematic review. J Pain Symptom Manage 2007 Nov 1; 34(5): 547–65

    Article  PubMed  CAS  Google Scholar 

  4. Quigley C. The role of opioids in cancer pain. BMJ 2005 Oct 8; 331(7520): 825–9

    Article  PubMed  Google Scholar 

  5. Kalso E, Edwards JE, Moore RA, et al. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004 Dec; 112(3): 372–80

    Article  PubMed  CAS  Google Scholar 

  6. Chappell D, Rehm M, Conzen P. Opioid-induced constipation in intensive care patients: relief in sight? Crit Care 2008; 12(4): 161

    Article  PubMed  Google Scholar 

  7. National Health Service Scotland. Constipation in palliative care [online]. Available from URL: http://www.palliativecareguidelines.scot.nhs.uk/documents/Constipationfinal.pdf [Accessed 2010 Apr 13]

  8. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: palliative care. V.1.2010 [online]. Available from URL: http://www.nccn.org/professionals/physician_gls/PDF/palliative.pdf [Accessed 2010 Apr 13]

  9. Wyeth Pharmaceuticals Inc. Relistor® (methylnaltrexone bromide) subcutaneous injection: US prescribing information [online]. Available from URL: http://www.wyeth.com/content/showlabeling.asp?id=499 [Accessed 2010 Apr 13]

  10. Yuan CS, Foss JF. Gastric effects of methylnaltrexone on μ, κ, and δ opioid agonists induced brainstem unitary responses. Neuropharmacology 1999 Mar; 38(3): 425–32

    Article  PubMed  CAS  Google Scholar 

  11. Valentino RJ, Herling S, Woods JH, et al. Quaternary naltrexone: evidence for the central mediation of discriminative stimulus effects of narcotic agonists and antagonists. J Pharmacol Exp Ther 1981 Jun; 217(3): 652–9

    PubMed  CAS  Google Scholar 

  12. van Hoogmoed LM, Boscan PL. In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure. Equine Vet J 2005 Jul; 37(4): 325–8

    Article  PubMed  Google Scholar 

  13. Yuan CS, Foss JF, Moss J. Effects of methylnaltrexone on morphine-induced inhibition of contraction in isolated guinea-pig ileum and human intestine. Eur J Pharmacol 1995 Mar 24; 276(1-2): 107–11

    Article  PubMed  CAS  Google Scholar 

  14. Gmerek DE, Cowan A, Woods JH. Independent central and peripheral mediation of morphine-induced inhibition of gastrointestinal transit in rats. J Pharmacol Exp Ther 1986 Jan; 236(1): 8–13

    PubMed  CAS  Google Scholar 

  15. Bianchi G, Fiocchi R, Tavani A, et al. Quaternary narcotic antagonists’ relative ability to prevent antinociception and gastrointestinal transit inhibition in morphine-treated rats as an index of peripheral selectivity. Life Sci 1982 May 31; 30(22): 1875–83

    Article  PubMed  CAS  Google Scholar 

  16. Walker MJ, Le AD, Poulos CX, et al. Role of central versus peripheral opioid receptors in analgesia induced by repeated administration of opioid antagonists. Psychopharmacology (Berl) 1991; 104(2): 164–6

    Article  CAS  Google Scholar 

  17. Russell J, Bass P, Goldberg LI, et al. Antagonism of gut, but not central effects of morphine with quaternary narcotic antagonists. Eur J Pharmacol 1982 Mar 12; 78(3): 255–61

    Article  PubMed  CAS  Google Scholar 

  18. Yuan CS, Wei G, Foss JF, et al. Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: a double-blind randomized placebo-controlled trial. J Pharmacol Exp Ther 2002 Jan; 300(1): 118–23

    Article  PubMed  CAS  Google Scholar 

  19. Yuan CS, Foss JF, Osinski J, et al. The safety and efficacy of oral methylnaltrexone in preventing morphine-induced delay in oral-cecal transit time. Clin Pharmacol Ther 1997 Apr; 61(4): 467–75

    Article  PubMed  CAS  Google Scholar 

  20. Murphy DB, Sutton JA, Prescott LF, et al. Opioid-induced delay in gastric emptying: a peripheral mechanism in humans. Anesthesiology 1997 Oct; 87(4): 765–70

    Article  PubMed  CAS  Google Scholar 

  21. Yuan CS, Foss JF, O’Connor M, et al. Methylnaltrexone prevents morphine-induced delay in oral-cecal transit time without affecting analgesia: a double-blind randomized placebo-controlled trial. Clin Pharmacol Ther 1996 Apr; 59(4): 469–75

    Article  PubMed  CAS  Google Scholar 

  22. Yuan CS, Foss JF, O’Connor M, et al. Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial. JAMA 2000 Jan 19; 283(3): 367–72

    Article  PubMed  CAS  Google Scholar 

  23. Yuan CS, Foss JF, O’Connor M, et al. Effects of intravenous methylnaltrexone on opioid-induced gut motility and transit time changes in subjects receiving chronic methadone therapy: a pilot study. Pain 1999 Dec; 83(3): 631–5

    Article  PubMed  CAS  Google Scholar 

  24. Slatkin N, Thomas J, Lipman AG, et al. Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients. J Support Oncol 2009 Jan–Feb; 7(1): 39–46

    PubMed  CAS  Google Scholar 

  25. Thomas J, Karver S, Austin Cooney G, et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med 2008 May 29; 358(22): 2332–43

    Article  PubMed  CAS  Google Scholar 

  26. European Medicines Agency. Relistor® (methylnaltrexone bromide solution) EU prescibing information [online]. Available from URL: http://www.ema.europa.eu/humandocs/PDFs/EPAR/relistor/emea-combined-h870en.pdf [Accessed 2010 Apr 13]

  27. Wang CZ, Li XL, Sun S, et al. Methylnaltrexone, a peripherally acting opioid receptor antagonist, enhances tumoricidal effects of 5-Fu on human carcinoma cells. Anticancer Res 2009 Aug; 29(8): 2927–32

    PubMed  CAS  Google Scholar 

  28. Singleton PA, Mambetsariev N, Lennon FE, et al. Methylnaltrexone potentiates the anti-angiogenic effects of mTOR inhibitors. J Angiogenes Res 2010; 2(1): 5

    Article  PubMed  Google Scholar 

  29. Singleton PA, Garcia JG, Moss J. Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor-induced angiogenesis. Mol Cancer Ther 2008 Jun; 7(6): 1669–79

    Article  PubMed  CAS  Google Scholar 

  30. Yuan CS, Sun S, Attele A, et al. Methylnaltrexone potentiates body weight and fat reduction with leptin. J Opioid Manag 2009 Nov 31; 5(6): 373–8

    PubMed  Google Scholar 

  31. Yuan CS, Wang CZ, Attele A, et al. Methylnaltrexone reduced body weight gain in ob/ob mice. J Opioid Manag 2009 Jul 31; 5(4): 213–8

    PubMed  Google Scholar 

  32. Portenoy RK, Thomas J, Boatwright MLM, et al. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage 2008 May 1; 35(5): 458–68

    Article  PubMed  CAS  Google Scholar 

  33. Chamberlain BH, Cross K, Winston JL, et al. Methylnaltrexone treatment of opioid-induced constipation in patients with advanced illness. J Pain Symptom Manage 2009 Nov; 38(5): 683–90

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements and Disclosures

The manuscript was reviewed by: F. Firenzuoli, Centre of Natural Medicine, S. Giuseppe Hospital, Empoli, Italy; M.D. Adolph, Department of Internal Medicine and Surgery, James Cancer Hospital, Ohio State University Medical Center, Columbus, Ohio, USA.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Karly P. Garnock-Jones & Kate McKeage

Authors
  1. Karly P. Garnock-Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kate McKeage
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karly P. Garnock-Jones.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Garnock-Jones, K.P., McKeage, K. Methylnaltrexone. Drugs 70, 919–928 (2010). https://doi.org/10.2165/11204520-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11204520-000000000-00000

Keywords

Search

Navigation