Cumulative Laxation Response with Methylnaltrexone: Implications for Hospitalized Patients with Advanced Illness and Opioid-Induced Constipation

Abstract

Background: Opioid-induced constipation (OIC) may increase the risk of fecal impaction and mortality in patients with advanced illness. Methylnaltrexone (MNTX) is efficacious for OIC. Objective: The purpose of this analysis was to evaluate cumulative rescue-free laxation response with repeat MNTX dosing in patients with advanced illness who were refractory to current laxative regimens and to assess the influence, if any, of poor functional status on response to MNTX treatment. Methods: This analysis included pooled data from patients with advanced illness and established OIC who were on a stable opioid regimen in a pivotal, randomized, placebo (PBO)-controlled clinical trial (study 302 [NCT00402038]) or a randomized, PBO-controlled Food and Drug Administration-required postmarketing study (study 4000 [NCT00672477]). Patients in study 302 received subcutaneous MNTX 0.15 mg/kg or PBO every other day, whereas those in study 4000 received MNTX 8 mg (body weight ≥38 to 2, and 63.4% had a primary diagnosis of cancer. Cumulative rescue-free laxation rates were significantly higher with MNTX than PBO 4- and 24-hours after doses 1, 2, and 3 (P < 0.0001), and between-treatment comparisons remained significant (P < 0.0001) regardless of performance status. The estimated time to first rescue-free laxation was shorter for patients receiving MNTX versus PBO. No new safety signals were identified. Conclusions: Repeated use of MNTX represents a safe and effective treatment for OIC in patients with advanced illness regardless of baseline performance status. ClinicalTrials.gov identifier: NCT00672477. (Curr Ther Res Clin Exp. 2023; 84:XXX–XXX)© 2023 Elsevier HS Journals, Inc.

Keywords

• Analgesia
• Cancer pain
• Constipation
• Laxatives
• Methylnaltrexone
• Opioid therapy