Efficacy of subcutaneous methylnaltrexone in the treatment of opioid-induced constipation: a responder post hoc analysis.

Abstract

OBJECTIVE:

Methylnaltrexone, a selective peripherally acting mu-opioid receptor antagonist, effectively treats opioid-induced constipation (OIC) in patients with advanced illness and shows efficacy in patients with chronic nonmalignant pain. The objective was to identify patients who achieved maximal treatment effect based on response to initial four methylnaltrexone doses.

DESIGN:

A post hoc analysis of a randomized, double-blind, placebo-controlled study evaluating patients with OIC and chronic nonmalignant pain who received 12 mg subcutaneous methylnaltrexone daily for 4 weeks was performed to determine if response to the first four methylnaltrexone doses predicted overall response during the study. Patients receiving ≥8 doses were included.

OUTCOME MEASURES:

Patients having ≥3 rescue-free bowel movements (RFBMs)/week; change from baseline in RFBMs/week; percentage of doses with RFBMs within 4 hours after dosing.

RESULTS:

Of 137 patients, 58 patients (42.3%) had RFBMs after ≥2 of four doses. Among those with response to ≥2 of four doses, 81% had ≥3 RFBMs/week vs. 43% for those with response to <2 of four (P < 0.0001). Those with RFBMs after ≥2 of first four doses averaged 4.8 RFBMs/week vs. 2.0 RFBMs/week for those with <2 of four (P < 0.0001). Percentage of subsequent injections resulting in RFBMs within 4 hours was 45.9 ± 27.6 for those with response to ≥2 of four doses vs. 17.1 ± 19.1 for those with response to <2 of four (P < 0.0001). Abdominal pain was the most frequently reported adverse event.

CONCLUSION:

Early response to ≥2 of first four doses of methylnaltrexone identified patients who demonstrated a particularly robust effect of treatment over the duration of use.

• Authors: Edward Michna, Arnold J Weil, Marc Duerden, Seth Schulman, Wenjin Wang, Evan Tzanis, Haiying Zhang, Dahong Yu, Amy Manley, Bruce Randazzo
• Journal: Pain medicine (Malden, Mass.) (Pain Med) Vol. 12 Issue 8 Pg. 1223-30 (Aug 2011) ISSN: 1526-4637 [Electronic] England
• PMID: 21810165 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Wiley Periodicals, Inc.

Chemical References

• Analgesics, Opioid
• Narcotic Antagonists
• Placebos
• Quaternary Ammonium Compounds
• methylnaltrexone
• Naltrexone

Topics

• Adult
• Analgesics, Opioid (adverse effects)
• Constipation (chemically induced, drug therapy)
• Double-Blind Method
• Female
• Humans
• Injections, Subcutaneous
• Male
• Middle Aged
• Naltrexone (administration & dosage, analogs & derivatives, therapeutic use)
• Narcotic Antagonists (administration & dosage, therapeutic use)
• Placebos
• Quaternary Ammonium Compounds (administration & dosage, therapeutic use)
• Treatment Outcome