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Allopurinol

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1. Allopurinol / lesinurad (Duzallo) - Gout

Allopurinol / lesinurad (Duzallo) - Gout 30 Churchill Place ? Canary Wharf ? London E14 5EU ? United Kingdom An agency of the European Union Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. 28 June 2018 EMA/474026/2018 Committee for Medicinal Products for Human Use (CHMP) Assessment report Duzallo International non-proprietary (...) name: allopurinol / lesinurad Procedure No. EMEA/H/C/004412/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Assessment report EMA/474026/2018 Page 2/100 Table of contents 1. Background information on the procedure 6 1.1. Submission of the dossier 6 1.2. Steps taken for the assessment of the product 6 2. Scientific discussion 8 2.1. Problem statement 8 2.1.1. Disease or condition 8 2.1.2. Epidemiology 8 2.1.3. Aetiology

2018 European Medicines Agency - EPARs

2. Allopurinol

Allopurinol Top results for allopurinol - Trip Database or use your Google+ account Find evidence fast ALL of these words: Title only Anywhere in the document ANY of these words: Title only Anywhere in the document This EXACT phrase: Title only Anywhere in the document EXCLUDING words: Title only Anywhere in the document Timeframe: to: Combine searches by placing the search numbers in the top search box and pressing the search button. An example search might look like (#1 or #2) and (#3 or #4 (...) ) Loading history... Population: Intervention: Comparison: Outcome: Population: Intervention: Latest & greatest articles for allopurinol The Trip Database is a leading resource to help health professionals find trustworthy answers to their clinical questions. Users can access the latest research evidence and guidance to answer their clinical questions. We have a large collection of systematic reviews, clinical guidelines, regulatory guidance, clinical trials and many other forms of evidence. If you

2018 Trip Latest and Greatest

3. Comparative cardiovascular risk of allopurinol versus febuxostat in patients with gout: a nation-wide cohort study (Abstract)

Comparative cardiovascular risk of allopurinol versus febuxostat in patients with gout: a nation-wide cohort study To compare cardiovascular (CV) risk among gout patients initiating allopurinol vs febuxostat.Using 2002-2015 Korean National Health Insurance Service data for the entire Korean population, we conducted a cohort study on gout patients initiating allopurinol or febuxostat. The primary outcome was a composite CV end point of myocardial infarction, stroke/transient ischaemic attack (...) , or coronary revascularization. Secondary outcomes were individual components of the primary outcome, and all-cause mortality. We used propensity score-matching with a 4:1 ratio for allopurinol and febuxostat initiators to control for confounding. Competing risk analyses were done for non-fatal outcomes accounting for deaths.We included 39 640 allopurinol initiators propensity score-matched on 9910 febuxostat initiators. The mean age was 59.1 years and 78.4% were male. The incidence rate per 100 person

2019 EvidenceUpdates

4. Risk of cutaneous adverse reactions associated with allopurinol or febuxostat in real-world patients: A nationwide study (Abstract)

Risk of cutaneous adverse reactions associated with allopurinol or febuxostat in real-world patients: A nationwide study Allopurinol carries a well-known risk of cutaneous adverse reactions (CARs). Although febuxostat, a xanthine-oxidase inhibitor with different chemical structure, has been considered an alternative to allopurinol, post-marketing case reports of life-threatening febuxostat-related CARs have been reported. We aimed to compare the risk of CARs between allopurinol and febuxostat (...) in real-world settings and to assess the impact of the market entry of febuxostat on allopurinol use and associated CARs.A nationwide study was conducted using Taiwan's National Health Insurance Research Database. In the new-user cohort study, patients who received their first prescriptions of allopurinol or febuxostat were included, and Poisson regression was used to estimate the incidence rate ratios (IRRs) of CARs. In the interrupted time series analysis, time series data on new users and incidence

2019 EvidenceUpdates

5. Heart disease and the risk of allopurinol-associated severe cutaneous adverse reactions: a general population-based cohort study Full Text available with Trip Pro

Heart disease and the risk of allopurinol-associated severe cutaneous adverse reactions: a general population-based cohort study Allopurinol is commonly prescribed for gout, and its clinical use may expand with ongoing trials assessing its potential cardiorenal benefits. Because heart disease has been suggested to be a risk factor for allopurinol-associated severe cutaneous adverse reactions, we sought to confirm this association in a Canadian general population cohort.We used population data (...) from British Columbia, Canada, to identify all incident allopurinol users between 1997 and 2015. We examined the association between heart disease (ischemic heart disease and heart failure) and the risk of hospital admission for severe cutaneous adverse reactions, adjusting for known and purported risk factors. We also evaluated the joint effects of combined clinical and demographic risk factors.Among 130 325 allopurinol initiators, 109 hospital admissions occurred for allopurinol-associated severe

2019 EvidenceUpdates

6. Maternal Allopurinol Prevents Cardiac Dysfunction in Adult Male Offspring Programmed by Chronic Hypoxia During Pregnancy Full Text available with Trip Pro

Maternal Allopurinol Prevents Cardiac Dysfunction in Adult Male Offspring Programmed by Chronic Hypoxia During Pregnancy Integrating functional and molecular levels, we investigated the effects of maternal treatment with a xanthine oxidase inhibitor on the programming of cardiac dysfunction in adult offspring using an established rat model of hypoxic pregnancy. Female Wistar rats were divided into normoxic or hypoxic (13% O2) pregnancy±maternal allopurinol treatment (30 mg kg-1 d-1). At 4 (...) %) and the cardiac expression of SERCA2a (+71.4%) were also elevated ( P<0.05), further linking molecular markers of cardiac stress and injury to dysfunction. Maternal allopurinol restored all functional and molecular indices of cardiac pathology. The data support a link between xanthine oxidase-derived oxidative stress in hypoxic pregnancy and cardiac dysfunction in the adult offspring, providing a target for early intervention in the developmental programming of heart disease.

2018 Hypertension (Dallas, Tex. : 1979)

7. Allopurinol for the treatment of chronic kidney disease: a systematic review

Allopurinol for the treatment of chronic kidney disease: a systematic review Allopurinolforthetreatmentofchronic kidneydisease:asystematicreview Nigel Fleeman, 1* Gerlinde Pilkington, 1 Yenal Dundar, 1 Kerry Dwan, 1 Angela Boland, 1 Rumona Dickson, 1 Hameed Anijeet, 2 Tom Kennedy 2 and Jason Pyatt 2 1 Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK 2 Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK *Corresponding author Declared (...) . Allopurinol (Zyloric ® , Aspen) is a drug commonly used to treat hyperuricaemia in patients with gout. Evidence is emerging that it may also have a role to play in slowing down the progression of CKD and reducing the risk of CVD. Objectives The aim of this systematic review was to address the following research question: does allopurinol reduce mortality, the progression of chronic kidney disease or cardiovascular risk in people with CKD? Given the importance of adverse events (AEs) (common and rare

2014 NIHR HTA programme

8. Ultra-performance hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for simultaneous determination of allopurinol, oxypurinol and lesinurad in rat plasma: Application to pharmacokinetic study in rats. Full Text available with Trip Pro

Ultra-performance hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for simultaneous determination of allopurinol, oxypurinol and lesinurad in rat plasma: Application to pharmacokinetic study in rats. A fixed dose combination of lesinurad and allopurinol has been recently approved by USFDA and EMA for treatment of gout-associated hyperuricemia in patients who have not achieved target serum uric acid levels with allopurinol alone. In this study, an ultra (...) -performance hydrophilic interaction liquid chromatography (UPHILIC) coupled with tandem mass spectrometry method was developed and validated for simultaneous determination of allopurinol, oxypurinol and lesinurad in rat plasma. Liquid liquid extraction using ethyl acetate as extracting agent was used for samples extraction procedure. Acquity UPLC HILIC column (100 mm x 2.1, 1.7μm) was used for separation of allopurinol, oxypurinol, lesinurad and internal standard (5-Florouracil). The mobile phase

2019 PLoS ONE

9. Assessment of Cardiovascular Risk in Older Patients with Gout Initiating Febuxostat versus Allopurinol: A Population-Based Cohort Study Full Text available with Trip Pro

Assessment of Cardiovascular Risk in Older Patients with Gout Initiating Febuxostat versus Allopurinol: A Population-Based Cohort Study Hyperuricemia and gout are associated with an increased risk of cardiovascular disease. Xanthine oxidase inhibitors, allopurinol and febuxostat, are the mainstay of urate-lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout.Using US Medicare claims data (2008-2013), we conducted a cohort study for comparative (...) cardiovascular safety of initiating febuxostat versus allopurinol among patients with gout ≥65 years of age. The primary outcome was a composite end point of hospitalization for myocardial infarction or stroke. Secondary outcomes were individual end points of hospitalization for myocardial infarction, stroke, coronary revascularization, new and recurrent heart failure, and all-cause mortality. We used propensity score matching with a ratio of 1:3 to control for confounding. We estimated incidence rates

2018 EvidenceUpdates

10. Effect of administration of allopurinol on postoperative outcomes in patients undergoing intracardiac repair of tetralogy of Fallot Full Text available with Trip Pro

Effect of administration of allopurinol on postoperative outcomes in patients undergoing intracardiac repair of tetralogy of Fallot To determine effects of allopurinol administration on outcomes following intracardiac repair of tetralogy of Fallot (TOF).Fifty patients undergoing TOF repair were randomized to 2 groups of 25 each: the allopurinol group (n = 25) and the placebo group (n = 25). Postoperatively, inotropic score, rhythm, duration of mechanical ventilation, cardiac output, intensive (...) care unit (ICU) stay, and hospital stay were assessed. Plasma troponin-I, superoxide dismutase (SOD), interleukin (IL) 1-ß, IL-6, and malondialdehyde were measured serially.Inotropic score was lower in the allopurinol compared with placebo group (11.04 ± 5.70 vs 17.50 ± 7.83; P = .02). Duration of ICU and hospital stay was lower in the allopurinol group. Plasma levels of SOD preoperative were (2.87 ± 1.21 U/mL vs 4.5 ± 2.08 U/mL; P = .012), immediately following release of crossclamp (2.32 ± 0.98 U

2018 EvidenceUpdates

11. Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment Full Text available with Trip Pro

Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment Clinicians are often cautious about use of allopurinol in patients with gout when renal function declines.To assess the association of allopurinol use in gout with the risk of developing chronic kidney disease stage 3 or higher.A time-stratified propensity score-matched, population-based, prospective cohort study of individuals with newly diagnosed gout who initiated allopurinol (≥300 mg/d) compared with those who did (...) not initiate allopurinol, using the Health Improvement Network (THIN), a United Kingdom general practitioner electronic health records database, was carried out. The data were analyzed using Cox proportional hazards regression. Among adults aged 18 to 89 years with newly diagnosed gout, we propensity score matched 4760 initiators of allopurinol (≥300 mg/d) to the same number of noninitiators of allopurinol, excluding those with chronic kidney disease stage 3 or higher or urate-lowering therapy use before

2018 EvidenceUpdates

12. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. Full Text available with Trip Pro

Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease.We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease (...) ; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization).In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85

2018 NEJM Controlled trial quality: predicted high

13. Starting allopurinol in acute gout

Starting allopurinol in acute gout Starting allopurinol in acute gout – Morsels of Evidence \t\t\t\r\n\t\t\t \t\t\t\r\n\t\t\t Like this: Like Loading... ","author":{"@type":"Person","name":"Michael Tam"},"image":["https:\/\/evidencebasedmedicine.com.au\/wp-content\/uploads\/2015\/10\/MO20151030.png"]} Toggle search form Toggle navigation Evidence-based medicine for general practitioners Oct 30 2015 Starting allopurinol in acute gout By in , Journal reference: Hill EM, Sky K, Sit M, Collamer (...) A, Higgs J. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol 2015;21(3):120-5. Link: Published: April 2015 Evidence cookie says… It is unclear what effect starting allopurinol in acute gout has on symptoms, due to the lack of good evidence. it may be preferable to avoid starting allopurinol in an acute attack this should not be a dogmatic stance Clinical scenario Zhongyu, a 50-year-old allied health practitioner presented with a recurrence of podagra

2015 Morsels of Evidence

14. Allopurinol for chronic gout. (Abstract)

Allopurinol for chronic gout. Allopurinol, a xanthine oxidase inhibitor, is considered one of the most effective urate-lowering drugs and is frequently used in the treatment of chronic gout.To assess the efficacy and safety of allopurinol compared with placebo and other urate-lowering therapies for treating chronic gout.We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE on 14 January 2014. We also handsearched the 2011 to 2012 American College (...) of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts, trial registers and regulatory agency drug safety databases.All randomised controlled trials (RCTs) or quasi-randomised controlled clinical trials (CCTs) that compared allopurinol with a placebo or an active therapy in adults with chronic gout.We extracted and analysed data using standard methods for Cochrane reviews. The major outcomes of interest were frequency of acute gout attacks, serum urate normalisation, pain, function

2014 Cochrane

15. Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-year follow up of the ALLO-trial. Full Text available with Trip Pro

Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-year follow up of the ALLO-trial. To evaluate the long-term neurodevelopmental and behavioral outcome of antenatal allopurinol treatment during suspected fetal hypoxia.We studied children born from women who participated in a randomized double-blind placebo controlled multicenter study (ALLO-trial). Labouring women in whom the fetus was suspected to have fetal (...) hypoxia were randomly allocated to receive allopurinol or placebo. At 5 years of age, the children were assessed with 2 parent reported questionnaires, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL). A child was marked abnormal for ASQ if it scored below 2 standard deviation under the normative mean of a reference population in at least one domain. For CBCL, a score above the cut-off value (95th percentile for narrowband scale, 85th percentile for broadband scale

2018 PLoS ONE Controlled trial quality: predicted high

16. Promising effects of xanthine oxidase inhibition by allopurinol on autonomic heart regulation estimated by heart rate variability (HRV) analysis in rats exposed to hypoxia and hyperoxia. Full Text available with Trip Pro

Promising effects of xanthine oxidase inhibition by allopurinol on autonomic heart regulation estimated by heart rate variability (HRV) analysis in rats exposed to hypoxia and hyperoxia. It has long been suggested that reactive oxygen species (ROS) play a role in oxygen sensing via peripheral chemoreceptors, which would imply their involvement in chemoreflex activation and autonomic regulation of heart rate. We hypothesize that antioxidant affect neurogenic cardiovascular regulation through (...) activation of chemoreflex which results in increased control of sympathetic mechanism regulating heart rhythm. Activity of xanthine oxidase (XO), which is among the major endogenous sources of ROS in the rat has been shown to increase during hypoxia promote oxidative stress. However, the mechanism of how XO inhibition affects neurogenic regulation of heart rhythm is still unclear.The study aimed to evaluate effects of allopurinol-driven inhibition of XO on autonomic heart regulation in rats exposed

2018 PLoS ONE

17. Correction: Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage. Full Text available with Trip Pro

Correction: Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage. [This corrects the article DOI: 10.1371/journal.pone.0179199.].

2018 PLoS ONE

18. Treatment with Allopurinol is Associated with Lower Risk of Acute Kidney Injury in Patients with Gout: A Retrospective Analysis of a Nested Cohort Full Text available with Trip Pro

Treatment with Allopurinol is Associated with Lower Risk of Acute Kidney Injury in Patients with Gout: A Retrospective Analysis of a Nested Cohort Gout is characterized by recurrent episodes of acute inflammation of joint structures, called gout flares, and flares are commonly treated with nonsteroidal anti-inflammatory drugs (NSAIDs). The objective of the study was to evaluate risk factors associated with acute kidney injury (AKI) attributed to NSAIDs in a cohort of patients who were exposed (...) associated with higher risk of renal events. Other variables previously described in the literature, such as previous chronic renal disease, use of diuretics, and presence of previous vascular events, were also independently associated with increased risk of AKI. Interestingly, patients who had been previously prescribed allopurinol showed a lower risk of acute renal events.In addition to classic risk factors, the number of flares and extensive joint distribution were associated with higher risk

2017 Rheumatology and therapy

19. Comparative efficacy and safety of lesinurad-allopurinol combination therapy in gout patients with an inadequate response to standard-of-care allopurinol: a systematic review with network meta-analysis

Comparative efficacy and safety of lesinurad-allopurinol combination therapy in gout patients with an inadequate response to standard-of-care allopurinol: a systematic review with network meta-analysis Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files

2018 PROSPERO

20. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Human Leukocyte Antigen-B (HLA-B) Genotype and Allopurinol Dosing

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Human Leukocyte Antigen-B (HLA-B) Genotype and Allopurinol Dosing Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Human Leukocyte Antigen B (HLA-B) Genotype and Allopurinol Dosing: 2015 Update YSaito 1 ,LKStamp 2 ,KECaudle 3 ,MSHershfield 4 ,EMMcDonagh 5 ,JTCallaghan 6,7,8 ,WTassaneeyakul 9 , TMushiroda 10 ,NKamatani 11 ,BRGoldspiel 12 ,EJPhillips 13,14 ,TEKlein 5 andMTMLee 15,16,17 The Clinical (...) and information that would modify prescribing recommendations pertaining to gene speci?c alleles and nomenclature are updated periodically on the PharmGKB website. Furthermore, published CPIC guidelines are currently systematically reviewed for updates periodically. The CPIC Guideline for HLA-B Genotype and Allopurinol Dosing was originally published in February 2013. 2 To update this guideline, we conducted a focused review of the literature published between 1966 to October 2014 on HLA genotype

2015 Clinical Pharmacogenetics Implementation Consortium

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