Methylnaltrexone for opioid-induced constipation: review and meta-analyses for objective plus subjective efficacy and safety outcomes

Siemens, Waldemar; Becker, Gerhild

doi:10.2147/tcrm.s80749

Cited by 37 publications

(36 citation statements)

References 40 publications

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“…In phase III studies, both substances have been shown to be highly effective and tolerable [30][31][32]; both drugs may be combined with all available opioid regimes irrespective of the choices of substance, medication routes, or dosing.…”

Section: Secretagoguesmentioning

confidence: 99%

Medical Therapy of Constipation: Current Standards and Beyond

Andresen

Layer²

2018

Visc Med

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Chronic constipation is a very common medical problem with relevant impact on the patients' quality of life. Modern definitions recognize constipation as a polysymptomatic disorder, including various aspects of disturbed defecation. Current guidelines recommend a stepwise approach in the management of chronic constipation. Isolated or concomitant evacuation disorders should be identified and may need differential/additional treatment. Baseline measures include lifestyle components and bulking agents. The next step recommends treatment with conventional laxatives. In refractory patients, modern medical therapies, such as the prokinetic prucalopride or the secretagogues linalotide or lubiprostone, may be used effectively. For patients with opioid-induced constipation, the modern concept of peripherally acting µ-opioid antagonists has shown to successfully improve this increasing medical problem and even to potentially increase survival time in terminally ill patients on opioid therapy. Prolonged-released oral naloxone (in fixed combination with oxycodone), oral naloxegol or naldemedine, and subcutaneous methylnaltrexone have all demonstrated good efficacy and tolerability in the treatment of opioid-induced constipation. To adequately apply stepwise treatment algorithms, a simple tool to identify treatment failure may improve patient care.

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Section: Secretagoguesmentioning

confidence: 99%

Medical Therapy of Constipation: Current Standards and Beyond

Andresen

Layer²

2018

Visc Med

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“…Several previous reviews on the similar topic have been published [22][23][24][25][26][27][28][29]. Six of them evaluated the treatment of OIC with different pharmacological therapies, mainly μ opioid receptor antagonists, including methylnaltrexone [22][23][24][25][26][27].…”

Section: Comparison With Existing Literaturementioning

confidence: 99%

Efficacy and Safety of Methylnaltrexone for the Treatment of Opioid-Induced Constipation: A Meta-analysis of Randomized Controlled Trials

Zhang

Zhou

2020

Preprint

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Background: Opioid-induced constipation (OIC) is a distressing side effect during opioid analgesia and is mainly mediated by gastrointestinal μ opioid receptors. Methylnaltrexone, a peripheral μ opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may alleviate OIC without reversing analgesia. We performed a meta-analysis to assess the efficacy and safety of methylnaltrexone for the treatment of OIC.Methods: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials that compared methylnaltrexone with placebo for the treatment of OIC. The primary efficacy outcome was rescue-free bowel movement (RFBM) within 4 hours after the first dose. Secondary efficacy outcomes included RFBM within 24 hours after the first dose, RFBM ≥3 times per week, and need take rescue laxatives. The primary safety outcome was any adverse events. Secondary safety outcomes included abdominal pain, diarrhea, nausea, vomiting, and flatulence. Relative risks (RR) and 95% confidence interval (CI) were pooled using random-effects model with the intention-to-treat principle. We used the GRADE approach to assess the certainty of the evidence.Results: Eight trials with 2,034 participants were included. Compared with placebo, methylnaltrexone significantly increased RFBM within 4 hours after the first dose (8 trials; 1,833 participants; RR 3.74, 95% CI 3.02-4.62; I2 = 0%; high-certainty evidence), RFBM within 24 hours after the first dose (2 trials; 614 participants; RR 1.98, 95% CI 1.52-2.58; I2 = 9%; moderate-certainty evidence), and RFBM ≥3 times per week (3 trials; 1,396 participants; RR 1.33, 95% CI 1.17-1.52; I2 = 0%; moderate-certainty evidence) and decreased need to take rescue laxatives (3 trials; 807 participants; RR 0.73, 95% CI 0.63-0.85; I2 = 0%; moderate-certainty evidence). For safety outcomes, there was no difference in any adverse events between the two groups (8 trials; 2,034 participants; RR 1.11, 95% CI 0.99-1.23; I2 = 34%; moderate-certainty evidence), including diarrhea, nausea, vomiting, and flatulence; but for the most commonly reported adverse events, the abdominal pain was higher in methylnaltrexone group than that in placebo group (6 trials; 1,813 participants; RR 2.30, 95% CI 1.29-4.08; I2 = 62%; moderate-certainty evidence).Conclusions: Methylnaltrexone is an effective and safe drug for treating OIC. But the safety of abdominal pain should be considered.Trial registration: PROSPERO (CRD42020187290).

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“…Abhängig vom Dosierungsverhältnis vom jeweiligen Opioid-Agonist zu Antagonist bleibt allerdings bei intakter Leberfunktion eine systemische Antagonisierung des Agonisten weitestgehend aus und es resultiert eine fast ausschließlich periphere Antagonisierung an den μ-Rezeptoren. Der Einsatz von PAMORAs (peripherally acting μ-opioid receptor antagonist) kann unabhängig vom Dosierungsverhältnis des Agonisten zum Antago- Ähnliche Ergebnisse werden auch für den PAMORA Methylnaltrexon gesehen; dazu sei auf eine Zusammenfassung die Originalarbeiten in den aktuellen Übersichten von Sonu et al [27], sowie Siemens und Becker verwiesen [28]: So kann auch unter Methylnaltrexon gegenüber Placebo Signifikanz für die Beschleunigung der Darmperistaltik gezeigt werden, wobei Methylnaltrexon in einer Publikation 68 gegenüber 45 % Placebo erreichte (0,009). Der Parameter "rescue-free bowel movement" (RFBM) bzw.…”

Section: Diagnoseunclassified

Nebenwirkungsmanagement der Opioid-Therapie

Wirz¹

2019

Laryngo-Rhino-Otol

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ZusammenfassungÜber 6 Millionen Menschen in Deutschland leiden unter stark beeinträchtigenden chronischen Schmerzen. Wegen der begrenzten analgetischen Effektivität und der Toxizität von Analgetika der Stufe 1 des WHO-Stufenschemas ist der Einsatz von Opioiden (Stufe 2 und 3) oft die einzige Therapieoption. Die hohe Inzidenz von Opioid-Nebenwirkungen bedingt jedoch eine hohe Abbruchrate. Daher beruht der Erfolg einer Opioid-Schmerztherapie entscheidend auch auf dem Management der Verträglichkeit und der Sicherheit der Behandlung. Die meisten Opioid-Nebenwirkungen, wie z. B. Übelkeit oder Sedierung, treten überwiegend in der Anfangsphase der Therapie auf. Die Opioid-induzierte Obstipation dagegen kann für die gesamte Dauer der Opioid-Therapie persistieren. Laxantien als Erstlinientherapie lösen das Problem nur bei einem Teil der Betroffenen. Als Zweilinientherapie können Opioid-Rezeptorantagonisten eingesetzt werden, wie Naloxon, oral applizierbares Naloxegol oder subkutanes Methylnaltrexon. Auch das Management weiterer häufiger Opioid-Nebenwirkungen wie Übelkeit und Erbrechen, Sedierung, Pruritus, Miktionsstörung und weiteren wird vorgestellt.

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Methylnaltrexone for opioid-induced constipation: review and meta-analyses for objective plus subjective efficacy and safety outcomes

Cited by 37 publications

References 40 publications

Medical Therapy of Constipation: Current Standards and Beyond

Medical Therapy of Constipation: Current Standards and Beyond

Efficacy and Safety of Methylnaltrexone for the Treatment of Opioid-Induced Constipation: A Meta-analysis of Randomized Controlled Trials

Nebenwirkungsmanagement der Opioid-Therapie

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