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Naloxegol

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https://www.readbyqxmd.com/read/28554659/naloxegol-an-opioid-antagonist-with-reduced-cns-penetration-mode-of-action-and-human-relevance-for-rat-testicular-tumours
#1
Håkan Andersson, Terri Mitchard, Nakpangi Johnson, Eike Floettmann
Naloxegol is an opioid antagonist which has been developed for the treatment of patients with opioid induced constipation. In the nonclinical safety program naloxegol was shown to have a very benign toxicity profile. In the rat, but not the mouse, 2-year carcinogenicity study a change in tumour pattern with an increase in testicular Leydig cell tumours (LCT) was observed after dosing at high (supra-pharmacological) concentrations. To establish the basis of the increase in LCT and to assess its potential relevance to humans, studies to exclude and potentially identify mode-of-action (MoA) were performed...
May 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28548207/pharmacometric-modeling-of-naloxegol-efficacy-and-safety-impact-on-dose-and-label
#2
N Al-Huniti, D Zhou, H Xu, S Aksenov, K H Bui, R Fox, G Helmlinger, D Stanski
Naloxegol is a peripherally acting μ-opioid receptor antagonist that was developed for the treatment of opioid-induced constipation. Modeling and simulation of naloxegol efficacy and tolerability informed selection of doses for phase III studies and provided comprehensive dosage recommendations for the naloxegol US package insert.
May 26, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28504549/determination-of-naloxegol-in-human-biological-matrices
#3
Yan Li, Mark Hoffmann, Paul Severin
AIM: Naloxegol is an oral peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation. Sensitive, robust, bioanalytical methods were required to quantitate naloxegol in human biological matrices as part of the clinical development program. Results/methodology: Analytical plasma samples were prepared using Solid Phase Extraction (SPE) coupled with concentration. The method's linearity was established at 0.1-50 ng/ml with up to 100-fold dilution...
May 15, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28423917/management-of-opioid-induced-constipation-in-hospice-patients
#4
Leah Sera, Mary Lynn McPherson
BACKGROUND: Constipation is a common symptom in patients with advanced disease taking opioids. Opioid-induced constipation (OIC) is commonly treated with laxatives and stool softeners. Recently, newer agents have come to market which broaden options for patients in whom first-line therapies are not effective. OBJECTIVE: To determine what pharmacologic regimens are currently used in hospice programs to prevent and treat OIC, whether those regimens have changed with the introduction of newer agents and evidence discouraging the use of docusate, and whether hospice programs are standardizing the management of OIC...
January 1, 2017: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/28363231/-management-of-adverse-effects-of-opioid-therapy
#5
Stefan Wirz
More than 6 million people in Germany suffer from chronic pain which greatly impairs their wellbeing. Often the only therapeutic option is to use class 2 or 3 analgesic opioids in the WHO classification, as class 1 analgesics may be toxic or of limited efficacy. However, the high incidence of opioid side effects leads to high discontinuation rates. Thus, the success of opioid treatment is also highly dependent on the management of the safety and tolerability of the treatment. Most opioid side effects, such as nausea and sedation, predominantly occur in the initial phase of therapy...
April 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/28336575/pharmacologic-profile-of-naloxegol-a-peripherally-acting-%C3%A2%C2%B5-opioid-receptor-antagonist-for-the-treatment-of-opioid-induced-constipation
#6
Eike Floettmann, Khanh Bui, Mark Sostek, Kemal Payza, Michael Eldon
Opioid-induced constipation (OIC) is a common side effect of opioid pharmacotherapy for the management of pain because opioid agonists bind to µ-opioid receptors in the enteric nervous system (ENS). Naloxegol, a polyethylene glycol derivative of naloxol, which is a derivative of naloxone and a peripherally acting µ-opioid receptor antagonist, targets the physiologic mechanisms that cause OIC. Pharmacologic measures of opioid activity and pharmacokinetic measures of central nervous system (CNS) penetration were employed to characterize the mechanism of action of naloxegol...
May 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28176913/peripherally-acting-%C3%AE-opioid-receptor-antagonists-as-treatment-options-for-constipation-in-noncancer-pain-patients-on-chronic-opioid-therapy
#7
REVIEW
Joseph V Pergolizzi, Robert B Raffa, Marco Pappagallo, Charles Fleischer, Joseph Pergolizzi, Gianpietro Zampogna, Elizabeth Duval, Janan Hishmeh, Jo Ann LeQuang, Robert Taylor
Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28162705/-454-delayed-opioid-withdrawal-in-a-patient-receiving-naloxegol-a-case-report
#8
N Sekhri, N Knox
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28127938/an-open-label-randomized-bioavailability-study-of-alternative-methods-of-oral-administration-of-naloxegol-in-healthy-subjects
#9
Khanh Bui, Bruce Birmingham, Ulysses Diva, Bruce Berger
Naloxegol is a peripherally acting μ-opioid receptor antagonist approved as an orally administered tablet for the treatment of opioid-induced constipation. Patients with swallowing difficulties may benefit from alternative approaches to the oral administration of the whole-tablet formulation of naloxegol. This open-label, randomized, 4-period, 4-treatment, crossover, single-dose study (NCT02446171) evaluated the pharmacokinetic (PK) characteristics of crushed naloxegol 25-mg tablets (suspended in water) administered orally or by nasogastric tube and a naloxegol solution compared with the commercially available 25-mg tablet formulation in healthy volunteers...
January 27, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28059433/a-12-week-extension-study-to-assess-the-safety-and-tolerability-of-naloxegol-in-patients-with-noncancer-pain-and-opioid-induced-constipation
#10
Lynn Webster, Raj Tummala, Ulysses Diva, Jaakko Lappalainen
OBJECTIVE: To compare the long-term safety and tolerability of naloxegol with placebo in patients with opioid-induced constipation (OIC) and noncancer pain. DESIGN: Twelve-week, multicenter, randomized, double-blind, parallel-group phase 3 extension study (KODIAC-07, NCT01395524). SETTING: Clinical investigation centers in the United States. PATIENTS: Adult outpatients (N = 302) with confirmed OIC who had completed a 12-week pivotal phase 3 study (KODIAC-04, NCT01309841)...
November 2016: Journal of Opioid Management
https://www.readbyqxmd.com/read/28035588/clinical-pharmacokinetics-and-pharmacodynamics-of-naloxegol-a-peripherally-acting-%C3%A2%C2%B5-opioid-receptor-antagonist
#11
REVIEW
Khanh Bui, Diansong Zhou, Hongmei Xu, Eike Floettmann, Nidal Al-Huniti
Naloxegol is a peripherally acting µ-opioid receptor antagonist approved for use as an orally administered tablet (therapeutic doses of 12.5 and 25 mg) for the treatment of opioid-induced constipation. Over a wide dose range (i.e. single supratherapeutic doses up to 1000 mg in healthy volunteers), the pharmacokinetic properties of naloxegol appear to be time- and dose-independent. Naloxegol is rapidly absorbed, with mean time to maximum plasma concentration of <2 h. Following once-daily administration, steady state is achieved within 2-3 days and minimal accumulation is observed...
June 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27938897/translating-clinical-findings-into-the-patient-s-perspective-post-hoc-pooled-analysis-of-bowel-movement-changes-as-a-predictor-of-improvement-in-patients-opioid-induced-constipation-symptoms-and-outcomes
#12
Karin S Coyne, Jiat-Ling Poon, Christine Thompson, Yiqun Hu, Catherine J Datto, Mark Sostek
PURPOSE: Opioid-induced constipation (OIC) is a bothersome side effect of opioid use for the management of noncancer pain, affecting patients' health-related quality of life and chronic-pain management. The objective of this study was to examine the relationship between changes in the frequency of spontaneous bowel movements (SBMs) and changes in patient-reported outcomes (PROs) among patients with OIC treated with naloxegol. METHODS: Post hoc analyses were conducted using pooled data from two Phase III 12-week, placebo-controlled trials of naloxegol for the treatment of OIC (NCT01309841 and NCT01323790)...
January 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/27663572/cost-effectiveness-of-naloxegol-for-opioid-induced-constipation-in-the-uk
#13
Richard Lawson, James Ryan, Frederic King, Jo Wern Goh, Eszter Tichy, Kevin Marsh
BACKGROUND AND OBJECTIVES: Opioid-induced constipation (OIC) is the most common adverse effect reported in patients receiving opioids to manage pain. Initial treatment with laxatives provides inadequate response in some patients. Naloxegol is a peripherally acting µ-opioid receptor antagonist used to treat patients with inadequate response to laxative(s) (laxative inadequate responder [LIR]). A cost-effectiveness model was constructed from the UK payer perspective to compare oral naloxegol 25 mg with placebo in non-cancer LIR patients receiving opioids for chronic pain, and a scenario analysis of naloxegol 25 mg with rescue laxatives compared with placebo with rescue laxatives in the same patient population...
February 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/27582887/the-role-of-naloxegol-in-the-management-of-opioid-induced-bowel-dysfunction
#14
REVIEW
Wojciech Leppert, Jaroslaw Woron
Opioid-induced constipation (OIC) and other gastrointestinal (GI) symptoms of opioid-induced bowel dysfunction (OIBD) significantly deteriorate patients' quality of life and may lead to noncompliance with opioid schedule and undertreatment of pain. Although traditional oral laxatives are the first-line treatment of OIC, they do not address OIBD pathophysiology, and display numerous adverse effects. OIC treatment includes prokinetics (lubiprostone), opioid switch, and changing route of opioid administration...
September 2016: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/27486521/persistent-constipation-and-abdominal-adverse-events-with-newer-treatments-for-constipation
#15
Irene Sonu, George Triadafilopoulos, Jerry D Gardner
BACKGROUND: Clinical trials of several new treatments for opioid-induced constipation (OIC), chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) have focused on differences between subjects relieved of constipation with placebo and active treatment. Patients and clinicians however, are more interested in the probability these treatments provide actual relief of constipation and its associated symptoms. METHODS: We searched the medical literature using MEDLINE and Cochrane central register of controlled trials...
2016: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/27435972/population-exposure-response-modeling-of-naloxegol-in-patients-with-noncancer-related-pain-and-opioid-induced-constipation
#16
N Al-Huniti, J C Nielsen, M M Hutmacher, J Lappalainen, K Cantagallo, M Sostek
Naloxegol is a polyethylene glycol derivative of naloxone approved in the US as a once-daily oral treatment for opioid-induced constipation (OIC) in adults with chronic noncancer pain. Population exposure-response models were constructed based on data from two phase III studies comprising 1,331 adults with noncancer pain and OIC. In order to characterize the protocol-defined naloxegol responder rate, the number of daily spontaneous bowel movements (SBMs) was characterized by a longitudinal ordinal nonlinear mixed-effects logistic regression dose-response model, and the incidence of diary entry discontinuation was described by a time-to-event model...
July 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27417446/constipation-in-elderly-patients-with-noncancer-pain-focus-on-opioid-induced-constipation
#17
Sita Chokhavatia, Elizabeth S John, Mary Barna Bridgeman, Deepali Dixit
Constipation is a common and often debilitating condition in the elderly, which may be caused by underlying disease conditions, structural abnormalities in the bowel, and a variety of medications such as anticholinergics, antidepressants, and opiates. In this review, we focus on opioid-induced constipation (OIC), which is often underrecognized and undertreated in the elderly. When opioid therapy is initiated, healthcare providers are encouraged to evaluate risk factors for the development of constipation as part of a thorough patient history...
August 2016: Drugs & Aging
https://www.readbyqxmd.com/read/27342744/impact-of-treatment-with-naloxegol-for-opioid-induced-constipation-on-patients-health-state-utility
#18
Richard Lawson, Frederic King, Kevin Marsh, Arman Altincatal, Ali Cimen
INTRODUCTION: Opioid-induced constipation (OIC) is the most common side effect of opioid treatment. Treatment for OIC typically involves a laxative. However, some patients have an inadequate response to these (laxative inadequate responders, or LIR). This has led to the development of treatments such as naloxegol. This analysis estimates the impact of naloxegol on the health state utility of LIR patients, examines if this utility impact is driven by the change in OIC status, and estimates the utility impact of relief of OIC...
August 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27299937/simulation-and-prediction-of-the-drug-drug-interaction-potential-of-naloxegol-by-physiologically-based-pharmacokinetic-modeling
#19
D Zhou, K Bui, M Sostek, N Al-Huniti
Naloxegol, a peripherally acting μ-opioid receptor antagonist for the treatment of opioid-induced constipation, is a substrate for cytochrome P450 (CYP) 3A4/3A5 and the P-glycoprotein (P-gp) transporter. By integrating in silico, preclinical, and clinical pharmacokinetic (PK) findings, minimal and full physiologically based pharmacokinetic (PBPK) models were developed to predict the drug-drug interaction (DDI) potential for naloxegol. The models reasonably predicted the observed changes in naloxegol exposure with ketoconazole (increase of 13...
May 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27231750/management-of-opioid-induced-constipation
#20
REVIEW
David Prichard, Christine Norton, Adil E Bharucha
Up to 40% of patients taking opioids develop constipation. Opioid-induced constipation (OIC) may limit the adequate dosing of opioids for pain relief and reduce quality of life. Health professionals must therefore inquire about bowel function in patients receiving opioids. The management of OIC includes carefully re-evaluating the necessity, type and dose of opioids at each visit. Lifestyle modification and alteration of aggravating factors, the use of simple laxatives and, when essential, the addition of newer laxatives or opioid antagonists (naloxone, naloxegol or methylnaltrexone) can be used to treat OIC...
May 26, 2016: British Journal of Nursing: BJN
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