Peripherally acting μ‐opioid antagonist for the treatment of opioid‐induced constipation: Systematic review and meta‐analysis

Abstract

Background and Aim Opioid‐induced constipation (OIC) is a frequent adverse event (AE) that impairs patients' quality of life (QOL). Peripherally acting μ‐opioid receptor antagonists (PAMORAs) have been recognized as a treatment option for OIC, but the effect consistent across the studies has not been evaluated. Methods We conducted a quantitative meta‐analysis to explore the efficacy of PAMORA for OIC (registered with PROSPERO: CRD42018085298). We systematically searched randomized controlled trials (RCTs) in Medline, Embase, and Central databases. Change from baseline in spontaneous bowel movements, pooled proportion of responders, QOL, and AEs were calculated and compared with results in placebo cases. Results We included 31 RCTs with 7849 patients. A meta‐analysis revealed that patients under PAMORA therapy had considerably improved spontaneous bowel movement from baseline compared with those given placebo (20 RCTs; mean difference, 1.43; 95% confidence interval [CI], 1.18–1.68; n = 5622) and more responded (21 RCTs; risk ratio [RR], 1.81; 95% CI, 1.55–2.12; n = 4821). Moreover, QOL of patients receiving PAMORA was significantly better (8 RCTs; mean difference, −0.22; 95% CI, −0.28 to −0.17; n = 2884). AEs were increased significantly in the PAMORA group (26 RCTs; RR, 1.10; 95% CI, 1.06–1.15; n = 7715), especially in gastrointestinal disorders, whereas serious AEs were not significant (17 RCTs; RR, 1.04; 95% CI, 0.85–1.28; n = 5890). Conclusion Peripherally acting μ‐opioid receptor antagonist has been shown to be effective and durable for patients with OIC and is the only drug with confirmed evidence in meta‐analysis. The possibility of publication bias was the limitation of this study.

Perioperative Pain Management and Opioid Stewardship: A Practical Guide

“…Unique considerations exist in major colorectal surgery and are discussed in enhanced recovery guidelines [281]. Peripherally acting opioid antagonists have been developed to combat opioid-induced constipation with mixed results for clinical outcomes and cost-effectiveness related to postoperative ileus [459][460][461][462]. Naloxegol and alvimopan may have comparable efficacy in the postoperative period [463].…”

Aktualisierte S2k-Leitlinie chronische Obstipation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie & Motilität (DGNM) – April 2022 – AWMF-Registriernummer: 021–019

“…Die Wirksamkeit von Methylnaltrexon wurde untersucht in vier randomisierten kontrollierten Studien 415 416 417 418 , von denen drei zusätzlich in zwei Metaanalysen 419 420 ausgewertet wurden. Mehrere RCT zeigen die Wirksamkeit von Naldemedin und Naloxogol 413 421 422 423 424 425 426 . Dieses Statement bewegt sich analog zur S3-Leitlinie Palliativmedizin und LONTS.…”

“…[415][416][417][418], von denen drei zusätzlich in zwei Metaanalysen [419,420] ausgewertet wurden. Mehrere RCT zeigen die Wirksamkeit von Naldemedin und Naloxogol [413,[421][422][423][424][425][426]. Dieses Statement bewegt sich analog zur S3-Leitlinie Palliativmedizin und LONTS.…”

Opioid-Induced Constipation: Cost Impact of Approved Medications in the Emergency Department

“…The PAMORA methylnaltrexone (subcutaneous [SC] or oral) has shown efficacy in treating OIC and may be of utility when administered in the ED because of its rapid time to laxation (often within 4 h for the SC formulation) [13][14][15][16][17]. In a meta-analysis of PAMORA clinical trials, patients treated with a PAMORA experienced larger improvements in spontaneous bowel movements from baseline, and higher response rates, versus those treated with placebo [18]. Accordingly, it is possible that this efficacy will translate into reduced HRU and healthcare cost savings, but there is no evidence available to date among patients with OIC in US clinical practice.…”