Methylnaltrexone: a novel approach for the management of opioid-induced constipation in patients with advanced illness

Abstract

In April 2008, the US FDA granted approval to methylnaltrexone (Relistor^®), the first peripheral µ-opioid-receptor antagonist for the treatment of opioid-induced constipation in advanced-illness patients receiving palliative care and for whom other laxative therapies failed to achieve adequate results. Methylnaltrexone, a quaternary derivative of naltrexone, introduces a novel mechanism of action that selectively antagonizes the peripheral µ-receptors in the GI tract without effects on the CNS. In clinical trials, subcutaneous methylnaltrexone reversed opioid-induced constipation after the first dose in approximately 50–60% of the patients. In most of the cases, effective laxation occurred within 1 h. The therapeutic benefit was sustained in multiple-dose studies. Owing to the nature of the population studied, safety data are available for approximately 4 months of use. Although it is not the focus of this article, methylnaltrexone’s mechanism of action suggests it could be beneficial for other peripheral, opioid-induced adverse effects, such as opioid-related nausea, vomiting, urinary retention, pruritus or postoperative ileus.

Keywords::

• constipation
• laxative
• methylnaltrexone
• µ-opioid receptor antagonist
• opioid
• palliative care
• peripheral opioid antagonist receptor

Financial & competing interests disclosure

Charles von Gunten discloses that he has received research funding for the study of methylnaltrexone, and has received compensation from Progenics and Wyeth for describing results of clinical trials conducted at the Institute for Palliative Medicine at San Diego Hospice. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

Data from [108].