Methylnaltrexone: a novel approach for the management of opioid-induced constipation in patients with advanced illness.
In April 2008, the US FDA granted approval to methylnaltrexone (Relistor), the first peripheral micro-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 micro-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.
Diego
Laura
L
Universitat Pompeu Fabra, Department of Experimental and Health Sciences, Edifici Parc de Recerca Biomèdica de Barcelona, Carrer Dr. Aiguader, 88. 08003 Barcelona, Spain. ldiegod@sefap.org
Atayee
Rabia
R
Helmons
Pieter
P
von Gunten
Charles F
CF
D000701:Analgesics, Opioid / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D003248:Constipation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects; D017277:Drug Approval; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D054368:Laxatives / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010166:Palliative Care; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D054368:Laxatives; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone