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Methylnaltrexone
(Opioid-induced Constipation in the Chronic Pain Setting)
In May 2009, our collaborator, Wyeth, completed a phase 3 trial of methylnaltrexone in the chronic pain setting (press release). Results from this pivotal study would be included in a planned supplemental New Drug Application to the U.S. Food and Drug Administration. If approved for the treatment of opioid-induced constipation in the chronic pain setting, this would add a new indication for the use of RELISTOR in the United States.
About Opioid-induced Constipation in the Chronic Pain Setting
Opioids are analgesics -- drugs used to relieve pain or achieve analgesia. Approximately 10 million patients a year in the U.S. are prescribed opioids for 30 days or more to manage pain1. Opioids provide powerful pain relief, but also cause significant constipation. In a multinational internet-based survey of 322 patients with chronic pain taking daily oral opioids and laxatives, 81% of patients reported experiencing constipation while using their current opioid regimen and 45% reported less than 3 bowel movements per week2.
How methylnaltrexone works
Opioids relieve pain by interacting with receptors located in the brain and spinal cord, which comprise the central nervous system (CNS). At the same time, opioids also activate receptors outside the CNS, such as those in the gastrointestinal tract, often resulting in constipation.
Methylnaltrexone, a selective, peripherally acting, mu-opioid-receptor antagonist, decreases the constipating effects of opioids without diminishing the analgesic effects of opioids in the CNS. Because of its positive charge, methylnaltrexone has restricted ability to cross the blood-brain barrier. It reverses the peripheral action of opioids without affecting centrally-mediated pain relief.
As a result, methylnaltrexone decreases
the constipating effects on the gastrointestinal tract via receptors outside the
CNS without affecting centrally mediated analgesia (i.e., pain relief) via
receptors inside the CNS.
1 SDI Longitudinal Patient Data Year 2005
2 The Prevalence, Severity, and Impact of Opioid-Induced Bowel
Dysfunction: Results of a US and European Patient Survey (PROBE 1) Bell, et al.,
Jnl. Pain Medicine 2009; vol. 10, no. 1, p. 40