Methylnaltrexone Treatment of Opioid-Induced Constipation in Patients with Advanced Illness

Methylnaltrexone, a Peripherally acting mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, reverses opioid-induced constipation (OIC) without affecting analgesia. A double-blind, study in, patients with advanced illness and OIC demonstrated that methylnaltrexone significantly induced taxation within four hours after the. fist close compared with placebo. In this study, patients with advanced illness and OIC on stable doses of opioids and laxatives were randomized to methylnaltrexone 0.15 mg/kg (n = 62) or placebo (n = 71) subcutaneausly every other clay for two weeks. Laxation was assessed, daily. Constipation distress, bowel, status change, pain, laxative use, and opioid withdrawal, symptoms were assessed weekly using standardized scales. Additional analyses to further characterize response to methylnaltrexone revealed, that among patients with a bowel movement within four hours following the fist, dose, the median hinge to response was 0.5 hours for methylnaltrexone. Response rates among methylnaltrexone-treated patients who had responded to all previous closes were 57%-100% for closes two to seven. Among methylnaltrexone-treated patients who did not respond to the first, or to the first two consecutive closes, 35% and 26% responded to the second and third dose, respectively. Higher percentages of patients and clinicians rated bowel, stales as improved in the methylnaltrexone than the placebo group. Fewer methylnaltrexone than, placebo patients reported use. of common laxative types, particularly enemas, during the, study. Subcutaneous methylnaltrexone promptly and predictably induced taxation, improved constipation distress, and was associated with less laxative use in patients with advanced, illness and OIC. J Pain Symptom Manage (C) 2009;38:683-690. 2009 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.