PMID- 34893381 OWN - NLM STAT- MEDLINE DCOM- 20220304 LR - 20220304 IS - 0736-4679 (Print) IS - 0736-4679 (Linking) VI - 62 IP - 2 DP - 2022 Feb TI - First-Dose Efficacy of Methylnaltrexone in Patients with Severe Medical Illness and Opioid-Induced Constipation: A Pooled Analysis. PG - 231-239 LID - S0736-4679(21)00755-1 [pii] LID - 10.1016/j.jemermed.2021.10.012 [doi] AB - BACKGROUND: Opioid-induced constipation (OIC) is a frequent consequence of opioid analgesia that may increase patient risk for emergency department visits and hospitalization. Methylnaltrexone is a peripherally acting micro-opioid receptor antagonist indicated for the treatment of OIC. OBJECTIVE: To assess the safety and efficacy of a single methylnaltrexone dose. METHODS: Results were pooled from three randomized, placebo-controlled methylnaltrexone (MNTX) studies in opioid-treated patients with advanced illness and OIC, despite treatment with conventional laxatives. Baseline assessments included demographics, disease/treatment characteristics, and functional levels. Efficacy endpoints included rescue-free laxation (RFL) rates within 4 and 24 h, time to first RFL, pain score change, and adverse events (AEs) after a single MNTX dose or placebo. RESULTS: The analysis included 281 patients receiving MNTX and 237 receiving placebo. Mean age was 66.2 years for MNTX and 65.8 for placebo; approximately 50% were men. The most frequent primary diagnosis was cancer (MNTX = 70.5%; placebo = 66.2%) and most ( approximately 98%) were receiving at least one laxative at baseline. RFL occurred in 61.4% vs. 16.0%, and 72.1% vs. 40.1% MNTX vs. placebo patients, within 4 and 24 h of the initial dose, respectively. Relative to placebo, MNTX use reduced the time to first RFL, with most MNTX-treated patients achieving RFL within 2 h. Baseline and posttreatment pain scores were similar (p = 0.9556 vs. placebo for current and worst pain change from baseline), demonstrating that MNTX did not negatively affect opioid analgesia. Most AEs were gastrointestinal related and dissipated by the second dose. CONCLUSIONS: Methylnaltrexone provides early RFL without compromising analgesia in patients receiving chronic opioid therapy. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Peacock, W Frank AU - Peacock WF AD - Baylor College of Medicine, Houston, Texas. Electronic address: frankpeacock@gmail.com. FAU - Slatkin, Neal E AU - Slatkin NE AD - School of Medicine, University of California Riverside, Riverside, California; Salix Pharmaceuticals, Bridgewater, New Jersey. FAU - Israel, Robert J AU - Israel RJ AD - Bausch Health US, LLC, Bridgewater, New Jersey. FAU - Stambler, Nancy AU - Stambler N AD - Progenics Pharmaceuticals, Inc., a subsidiary of Lantheus Holdings Inc., New York, New York. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20211207 PL - United States TA - J Emerg Med JT - The Journal of emergency medicine JID - 8412174 RN - 0 (Analgesics, Opioid) RN - 0 (Quaternary Ammonium Compounds) RN - 0RK7M7IABE (methylnaltrexone) RN - 5S6W795CQM (Naltrexone) SB - IM MH - Aged MH - *Analgesics, Opioid/adverse effects MH - Constipation/chemically induced/drug therapy MH - Humans MH - Male MH - Naltrexone/adverse effects/analogs & derivatives MH - *Opioid-Induced Constipation MH - Quaternary Ammonium Compounds OTO - NOTNLM OT - chronic pain OT - methylnaltrexone OT - narcotic antagonists OT - opioid-induced constipation OT - pain management EDAT- 2021/12/12 06:00 MHDA- 2022/03/05 06:00 CRDT- 2021/12/11 05:32 PHST- 2021/03/18 00:00 [received] PHST- 2021/07/16 00:00 [revised] PHST- 2021/10/12 00:00 [accepted] PHST- 2021/12/12 06:00 [pubmed] PHST- 2022/03/05 06:00 [medline] PHST- 2021/12/11 05:32 [entrez] AID - S0736-4679(21)00755-1 [pii] AID - 10.1016/j.jemermed.2021.10.012 [doi] PST - ppublish SO - J Emerg Med. 2022 Feb;62(2):231-239. doi: 10.1016/j.jemermed.2021.10.012. Epub 2021 Dec 7.