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JACC. Cardiovascular Interventions Aug 2019
Topics: Analgesics, Opioid; Coronary Artery Disease; Humans; Morphine; Naltrexone; Quaternary Ammonium Compounds; Ticagrelor; Treatment Outcome
PubMed: 31377266
DOI: 10.1016/j.jcin.2019.06.029 -
Clinical and Experimental... 2008Constipation is a significant problem related to opioid medications used to manage pain. This review attempts to outline the latest findings related to the therapeutic...
Constipation is a significant problem related to opioid medications used to manage pain. This review attempts to outline the latest findings related to the therapeutic usefulness of a μ opioid receptor antagonist, methylnaltrexone in the treatment of opioid-induced constipation. The review highlights methylnaltrexone bromide (Relistor™; Progenics/Wyeth) a quaternary derivative of naltrexone, which was recently approved in the United States, Europe and Canada. The Food and Drug Administration in the United States approved a subcutaneous injection for the treatment of opioid bowel dysfunction in patients with advanced illness who are receiving palliative care and when laxative therapy has been insufficient. Methylnaltrexone is a peripherally restricted, μ opioid receptor antagonist that accelerates oral-cecal transit in patients with opioid-induced constipation without reversing the analgesic effects of morphine or inducing symptoms of opioid withdrawal. An analysis of the mechanism of action and the potential benefits of using methylnaltrexone is based on data from published basic research and recent clinical studies.
PubMed: 21677823
DOI: 10.2147/ceg.s3889 -
Alimentary Pharmacology & Therapeutics Apr 2010Opioid-induced constipation is a common adverse event in patients with advanced illness and has a significant negative impact on patients' quality of life and costs.
BACKGROUND
Opioid-induced constipation is a common adverse event in patients with advanced illness and has a significant negative impact on patients' quality of life and costs.
AIM
To examine the cost-effectiveness of treating opioid-induced constipation with methylnaltrexone bromide (MNTX) plus standard care compared with standard care alone in patients with advanced illness who receive long-term opioid therapy from a third-party payer perspective in the Netherlands.
METHODS
A decision-analytical model was created in which advanced-illness patients with constipation were treated with MNTX plus standard care or standard care alone. Clinical efficacy in terms of percentage of patients with rescue-free laxation and time to rescue-free laxation were obtained from a randomized, controlled clinical study. Resource use, costs, utilities and mortality were obtained from published literature and supplemented with data from clinical experts.
RESULTS
Treatment with MNTX plus standard care results in more days without constipation symptoms. Cost of MNTX was mostly offset by reduction in other constipation-related costs. Thus, treating with MNTX plus standard care is cost-effective, with an incremental cost per QALY of 40,865 euro. Results were robust to changes in all parameters.
CONCLUSIONS
Although using MNTX may increase total costs, MNTX plus standard care is cost-effective in treating advanced-illness patients with opioid-induced constipation.
Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Constipation; Cost-Benefit Analysis; Humans; Laxatives; Middle Aged; Naltrexone; Narcotic Antagonists; Quality-Adjusted Life Years; Quaternary Ammonium Compounds; Terminally Ill; Young Adult
PubMed: 20096019
DOI: 10.1111/j.1365-2036.2010.04244.x -
American Journal of Therapeutics 2018
Topics: Aged, 80 and over; Colonic Pseudo-Obstruction; Drug Resistance; Humans; Injections, Subcutaneous; Intestine, Large; Naltrexone; Narcotic Antagonists; Neostigmine; Parasympathomimetics; Quaternary Ammonium Compounds; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 29509554
DOI: 10.1097/MJT.0000000000000743 -
Expert Review of Gastroenterology &... Jan 2013Opioids are the drugs of choice for treating moderate-to-severe pain, especially for patients in the end stage of cancer or other advanced illnesses, and also in... (Review)
Review
Opioids are the drugs of choice for treating moderate-to-severe pain, especially for patients in the end stage of cancer or other advanced illnesses, and also in critical care or for the treatment of chronic pain. Side effects such as nausea, pruritus, dizziness and constipation have to be controlled in order to use these drugs to their full potential. Opioid-induced bowel syndrome and constipation caused by activation of μ-receptors in the gut can have such distressing effects that some patients prefer to forego adequate pain control. Methylnaltrexone is a μ-opioid receptor antagonist that, unlike naltrexone or naloxone, does not pass the blood-brain barrier, and therefore does not impair the centrally mediated analgesic effect of opioids. It is licensed for the treatment of opioid-induced constipation in palliative care in more than 50 countries. This article presents practically relevant pharmacological data, basic research results and evidence from clinical research about methylnaltrexone, and outlines potential future therapeutic options for this promising drug.
Topics: Analgesics, Opioid; Constipation; Humans; Naloxone; Narcotic Antagonists; Pain; Palliative Care; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Treatment Outcome
PubMed: 23265145
DOI: 10.1586/egh.12.63 -
The Journal of Pediatric Pharmacology... 2022To evaluate the association between methylnaltrexone and urine output (UOP) in critically ill children with opioid-associated urinary retention.
OBJECTIVE
To evaluate the association between methylnaltrexone and urine output (UOP) in critically ill children with opioid-associated urinary retention.
METHODS
This retrospective study included patients admitted to the pediatric intensive care unit between December 1, 2019, and November 30, 2020, who received methylnaltrexone for opioid-associated oliguria (spontaneous UOP below 1 mL/kg/hr and at least 1 dose of an opioid within the preceding 6 hours).
RESULTS
Twenty-five patients (median age = 5.5 years, IQR 1.7-16.4; median weight = 19 kg, IQR 9-45) were included. Mean methylnaltrexone dose was 0.15 ± 0.006 mg/kg. A statistically significant increase in UOP from baseline to 6 hours following methylnaltrexone was observed (p = 0.001), but not all patients responded. Fourteen patients (56%) had no UOP following methylnaltrexone administration, while 11 (44%) demonstrated a robust increase (median = 0 mL/kg/hr at baseline [IQR 0-0] to 1.96 mL/kg/hr [IQR 1.08-2.22; p = 0.001]) within 6 hours following methylnaltrexone administration. Younger patients responded better than older patients (responder age = 2.5 years [IQR 0.8-7]) versus 11.4 years [IQR 1.75-17.5] for non-responders) (p = 0.04). Both intravenous (IV) and subcutaneous (SQ) routes were associated with an increase in UOP (IV, p = 0.04; SQ, p = 0.02). The effect persisted for up to 24 hours after administration. Sixty-four percent of patients required urinary catheter placement. Pain scores (averaged 6 hours before and after methylnaltrexone) remained unchanged (p = 0.44).
CONCLUSIONS
Methylnaltrexone may increase spontaneous UOP in some children with opioid-associated urinary retention, but urinary catheterization rates remain high.
PubMed: 35558358
DOI: 10.5863/1551-6776-27.4.373 -
The Cochrane Database of Systematic... Jan 2011Constipation is common in palliative care; it can generate considerable suffering due to the unpleasant physical symptoms. In the first Cochrane Review on effectiveness... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Constipation is common in palliative care; it can generate considerable suffering due to the unpleasant physical symptoms. In the first Cochrane Review on effectiveness of laxatives for the management of constipation in palliative care patients, published in 2006, no conclusions could be drawn because of the limited number of evaluations. This article describes the first update of this review.
OBJECTIVES
To determine the effectiveness of laxatives or methylnaltrexone for the management of constipation in palliative care patients.
SEARCH STRATEGY
We searched databases including MEDLINE and CENTRAL (The Cochrane Library) in 2005 and in the update to August 2010.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating laxatives for constipation in palliative care patients. In the update we also included RCTs on subcutaneous methylnaltrexone; an opioid-receptor antagonist that is now licensed for the treatment of opioid-induced constipation in palliative care when response to usual laxative therapy is insufficient.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data. The appropriateness of combining data from the studies depended upon clinical and outcome measure homogeneity.
MAIN RESULTS
We included seven studies involving 616 participants; all under-reported methodological features. In four studies the laxatives lactulose, senna, co-danthramer, misrakasneham, and magnesium hydroxide with liquid paraffin were evaluated. In three methylnaltrexone.In studies comparing the different laxatives evidence was inconclusive. Evidence on subcutaneous methylnaltrexone was clearer; in combined analysis (287 participants) methylnaltrexone, in comparison with a placebo, significantly induced laxation at 4 hours (odds ratio 6.95; 95% confidence interval 3.83 to 12.61). In combined analyses there was no difference in the proportion experiencing side effects, although participants on methylnaltrexone suffered more flatulence and dizziness. No evidence of opioid withdrawal was found. In one study severe adverse events, commonly abdominal pain, were reported that were possibly related to methylnaltrexone. A serious adverse event considered to be related to the methylnaltrexone also occurred; this involved a participant having severe diarrhoea, subsequent dehydration and cardiovascular collapse.
AUTHORS' CONCLUSIONS
The 2010 update found evidence on laxatives for management of constipation remains limited due to insufficient RCTs. However, the conclusions of this update have changed since the original review publication in that it now includes evidence on methylnaltrexone. Here it found that subcutaneous methylnaltrexone is effective in inducing laxation in palliative care patients with opioid-induced constipation and where conventional laxatives have failed. However, the safety of this product is not fully evaluated. Large, rigorous, independent trials are needed.
Topics: Analgesics, Opioid; Anthraquinones; Cathartics; Constipation; Humans; Lactulose; Magnesium Hydroxide; Naltrexone; Palliative Care; Paraffin; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic; Senna Extract
PubMed: 21249653
DOI: 10.1002/14651858.CD003448.pub3 -
Journal of Pain and Symptom Management Feb 2014
Review
Topics: Hospice Care; Humans; Internet; Naloxone; Naltrexone; Narcotic Antagonists; Palliative Care; Quaternary Ammonium Compounds
PubMed: 24512968
DOI: 10.1016/j.jpainsymman.2013.12.223 -
Pain Dec 2014
Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Male; Morphine; Narcotic Antagonists; Pain, Postoperative
PubMed: 25218602
DOI: 10.1016/j.pain.2014.09.008 -
Journal of Clinical Gastroenterology Jan 2023Opioid-induced constipation (OIC) is a common condition in older adults who may not be responsive to traditional laxative therapy. OIC is defined as new or worsening... (Review)
Review
Opioid-induced constipation (OIC) is a common condition in older adults who may not be responsive to traditional laxative therapy. OIC is defined as new or worsening constipation symptoms that occur with initiation of or altering the dose of opioid analgesia. For adult patients with OIC and noncancer pain, we recommend considering nonpharmacologic interventions (eg, dietary measures, increased physical activity, and biofeedback training) and over-the-counter laxatives, followed by prescription opioid receptor antagonists (methylnaltrexone, naloxegol, and naldemedine) if traditional over-the-counter laxatives fail. Other options may include lubiprostone, linaclotide, plecanatide, and prucalopride; however, these are not indicated for OIC specifically or studied in older adults. Because of the complex nature of absorption, distribution, metabolism, and excretion in the aging population, all agents used to treat OIC must be evaluated individually and reevaluated as patients continue to age. This review will serve as a guide to managing OIC in older adults.
Topics: Humans; Aged; Opioid-Induced Constipation; Analgesics, Opioid; Constipation; Laxatives; Aging
PubMed: 36504229
DOI: 10.1097/MCG.0000000000001801