Treatment of opioid-induced constipation in hospice patients with methylnaltrexone

Abstract

8279 Background: Methylnaltrexone (MNTX) is a selective opioid-receptor antagonist that does not cross the blood-brain barrier in humans. It has the potential to counteract the debilitating peripheral side effects of narcotic pain therapy without interruption of centrally-mediated analgesia or precipitation of withdrawal. MNTX is being developed for the treatment of opioid-induced constipation (OIC) which is refractory to laxatives and stool softeners. Methods: The activity and tolerability of MNTX were investigated in a series of phase 1 and 2 clinical trials. Normal subjects as well as patients receiving chronic opioids were treated with various doses of MNTX administered via intravenous and subcutaneous routes. Relief of OIC by subcutaneous MNTX was evaluated in hospice patients in phase 2 trials. Results: Results from completed studies demonstrate that MNTX was generally well tolerated and significantly reduced or prevented OIC, urinary retention, as well as other peripheral side effects of opioids. Subcutaneous MNTX provided rapid relief of OIC (median time ≈ 1 hr) in approximately 60% of terminally ill patients receiving active doses (≥ 5 mg). The median number of laxations per week increased to between 4 to 6 from ≤ 2 prior to baseline. The most frequent adverse events were transient mild abdominal cramping and flatulence. No evidence of opioid withdrawal or reversal of analgesia was observed in any clinical trial. Conclusions: MNTX is well tolerated and active in relieving OIC and other debilitating side effects of narcotic pain therapy. These findings strongly support further evaluation of subcutaneous MNTX in hospice patients experiencing OIC. Two pivotal phase 3 clinical trials in this setting are currently underway in the United States. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Progenics Pharmaceuticals, Inc. Progenics Pharmaceuticals, Inc. Progenics Pharmaceuticals, Inc.