Focus on Methylnaltrexone: A Selective Mu-Opioid Receptor Antagonist for the Treatment of Opioid-Induced Constipation

Objective: To review the literature available on the use of methylnaltrexone, a peripherally acting quaternary opioid antagonist, approved for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Data Sources: Primary literature and review articles were obtained via a MEDLINE search (1992-2009), using the key term methylnaltrexone. Additional articles were identified from the bibliographies of reviewed literature. Study Selection and Data Extraction: English-language articles identified from the data sources were reviewed. Randomized controlled trials were evaluated to assess the efficacy of methylnaltrexone. Data Synthesis: Opioids are the cornerstone of therapy for moderate-to-severe pain in patients with serious illness. The prevalence of OIC approaches 90% of patients with advanced illness. The symptoms associated with constipation include abdominal pain and distention, nausea and vomiting, and anorexia. For patients, this can become a significant source of distress and pain. Complications associated with fecal impaction, such as incontinence and confusion, may occur. OIC is currently managed with a variety of commercially available laxatives, stool softeners, suppositories, or enemas; however, they may be compromised by poor response, adverse effects such as bloating or cramping, or other outcomes that may impair quality of life, such as pill burden or unpredictable timing of laxation. Naloxone, an opioid antagonist, has been considered for the treatment of refractory OIC. It has low oral bioavailability but the relatively high doses required and variations in individual sensitivity to the drug may result in enough systemic absorption to reverse analgesia or induce central nervous system opioid withdrawal. To avoid these centrally mediated effects, new compounds that have little ability to cross the blood-brain barrier have been developed. Methylnaltrexone is a peripherally acting quaternary opioid antagonist approved for the treatment of OIC. It does not cross the blood-brain barrier in humans and offers the therapeutic potential to reverse adverse effects of opioid pain medications mediated by receptors peripherally located (eg, in the gastrointestinal tract). This effect is critical because it spares the opioid effects mediated at receptors in the central nervous system, most importantly analgesia, and has been proven to be effective in the treatment of OIC. Conclusions: Methylnaltrexone appears to be an effective treatment option for OIC.