Open AccessEfficacy of Subcutaneous Methylnaltrexone in the Treatment of Opioid‐Induced Constipation: A Responder Post Hoc Analysis
Author(s) -
Michna Edward,
Weil Arnold J.,
Duerden Marc,
Schulman Seth,
Wang Wenjin,
Tzanis Evan,
Zhang Haiying,
Yu Dahong,
Manley Amy,
Randazzo Bruce
Publication year - 2011
Publication title -
pain medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.893
H-Index - 97
eISSN - 1526-4637
pISSN - 1526-2375
DOI - 10.1111/j.1526-4637.2011.01189.x
Subject(s) - medicine , constipation , antagonist , opioid antagonist , opioid , post hoc analysis , anesthesia , naltrexone , (+) naloxone , receptor
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.