Febuxostat: updated advice for the treatment of patients with a history of major cardiovascular disease Skip to main contentCookies on GOV.UKWe use some essential cookies to make this website work.We’d like to set additional cookies to understand how you use GOV.UK, remember your settings and improve government services.We also use cookies set by other sites to help us deliver content from their services.Accept additional cookiesReject additional cookiesView cookies GOV.UKNavigation menuMenuSearch GOV.UKHomeDrug Safety UpdateFebuxostat: updated advice for the treatment of patients with a history of major cardiovascular diseaseCaution is required if prescribing febuxostat in patients with pre-existing major cardiovascular disease, particularly, in those with evidence of high urate crystal and tophi
Superiority of Low-Dose Benzbromarone Add-On to Low-Dose Febuxostat Compared With Febuxostat Monotherapy in Gout With Combined-Type Hyperuricemia. There is an unmet need for simpler urate-lowering therapy (ULT) regimens that achieve the serum urate target and improve the overall quality of gout care. We report a comparative effectiveness trial of febuxostat monotherapy versus benzbromarone add -on to low-dose febuxostat in gout specifically with combined renal urate underexcretion and overload. A prospective randomized trial was conducted on patients with combined-type hyperuricemia and estimated glomerular filtration rate >60 mL/min/1.73 m 1:1 randomly assigned to febuxostat and benzbromarone combination therapy (initially febuxostat at 20 mg/day, with benzbromarone at 25 mg/day added onto 20
Effects of allopurinol and febuxostat on uric acid transport and transporter expression in human umbilical vein endothelial cells. Uric acid induces radical oxygen species formation, endothelial inflammation, and endothelial dysfunction which contributes to the progression of atherosclerosis. Febuxostat inhibits BCRP- and allopurinol stimulates MRP4-mediated uric acid efflux in human embryonic kidney cells. We hypothesized that endothelial cells express uric acid transporters that regulate intracellular uric acid concentration and that modulation of these transporters by febuxostat and allopurinol contributes to their different impact on cardiovascular mortality. The aim of this study was to explore a potential difference between the effect of febuxostat and allopurinol on uric acid uptake
Efficacy and safety of the urate-lowering agent febuxostat in chronic heart failure patients with hyperuricemia: results from the LEAF-CHF study. Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure (CHF). To determine whether febuxostat, a urate-lowering agent, may improve clinical outcomes in CHF patients, we conducted a multicenter, prospective , randomized, open-label, blinded endpoint study with a treatment period of 24 weeks. We randomly assigned Japanese outpatients diagnosed with both CHF with reduced left ventricular ejection fraction (LVEF < 40%) and asymptomatic hyperuricemia (serum uric acid [UA] levels > 7.0 mg/dl and < 10.0 mg/dl) to either a febuxostat group (n = 51) or a control group (n = 50). The primary efficacy endpoint
Effect of the Xanthine Oxidase Inhibitor, Febuxostat, on WBC Count in Asymptomatic Hyperuricemia: Subanalysis of the Randomized PRIZE Study. The anti-inflammatory effects of the xanthine oxidase inhibitor, febuxostat, a urate-lowering agent, have been reported in animal studies. However, the anti-inflammatory effects of urate-lo wering therapy and its associated cardiovascular protective effects have not been fully determined in actual clinical practice. This study aimed to investigate the effect of febuxostat on white blood cell (WBC) count in patients with asymptomatic hyperuricemia and to assess for potential correlations between changes in WBC count and inflammatory biomarkers and atherosclerosis in this patient population. This was a post hoc subanalysis of the PRIZE study
Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial. A recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients
A Comparison of Gout Flares with the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-hoc Analysis of a Randomized Multicenter Trial. Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, non-inferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0-24 when ULT was initiated and titrated to a serum urate (sUA) goal of <6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular
Comparison of the therapeutic effects of febuxostat combined with a low-purine diet and allopurinol combined with a low-purine diet on the improvement of gout patients. To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout. In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three
Efficacy and Safety of Allopurinol and Febuxostat in Patients With Gout and CKD: Subgroup Analysis of the STOP Gout Trial. We conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD). Prespecified sub cohort analysis of a randomized controlled trial . & Participants: A sub study of the STOP Gout trial in participants with CKD. CKD was defined as an eGFR 30-59 mL/min/1.73 m at baseline. Trial participants with CKD and gout and serum urate (sUA) concentration ≥6.8 mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal sUA of <6.0 mg/dl (<5.0 mg/dl with tophi) (Phase 1
Population pharmacokinetic analysis of febuxostat with high focus on absorption kinetics and food effect. Febuxostat is commonly used in clinic for the treatment of hyperuricemia. Multiple-peak phenomenon has been observed in human plasma concentration-time profiles of febuxostat, but has not been paid enough attention in previous research. This study takes a pivotal step forward by conducting a comprehensive population pharmacokinetic (PopPK) analysis of febuxostat in a healthy Chinese cohort, with a central focus on delineating its absorption profile under contrasting fasting and fed conditions, while concurrently assessing the influence of food alongside other potential covariates on febuxostat's PK profile. The plasma concentration data used for modeling was obtained from two bioequivalence
Febuxostat leads to better cardiovascular outcomes compared to allopurinol in patients with advanced chronic kidney disease: A Population-based Cohort Study. Hyperuricemia is a risk factor for cardiovascular disease complications in patients with chronic kidney disease. The impact of febuxostat on cardiovascular disease in advanced chronic kidney disease remains unclear. This study aimed to explore the cardiovascular benefits of xanthine oxidase inhibitors, particularly febuxostat and allopurinol, in patients with advanced chronic kidney disease. A retrospective population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database (NHIRD) (2006-2017). The TriNetX dataset served as an external validation dataset. The study involved 13,187 patients
Febuxostat for treating chronic hyperuricaemia in adults with gout ACE Technology Guidances A Singapore Government Agency Website SEARCH Who We Are Organisational Structure Advisory Committees Committees We Serve Careers at ACE Healthcare Professionals ACE Clinical Guidances (ACGs) ACE CUES ACE Technology Guidances ACE Horizon Scanning Patients & Community Asthma Resources Plain English Summaries febuxostat on the Medication Assistance Fund (MAF) for treating chronic hyperuricaemia in adults with gout because of unacceptable cost-effectiveness compared with alternative treatments at the price proposed by the manufacturer. Febuxostat for chronic hyperuricaemia in adults with gout (2 May 2019) Febuxostat Plain English Summary (2 May 2019) 21 Feb 2022 Agency for Care Effectiveness (ACE)Who We
Febuxostat (Adenuric): increased risk of cardiovascular death and all-cause mortality in clinical trial in patients with a history of major cardiovascular disease Febuxostat (Adenuric): increased risk of cardiovascular death and all-cause mortality in clinical trial in patients with a history of major cardiovascular disease - GOV.UK Skip to main content Cookies on GOV.UKWe use some essential Search GOV.UK Search GOV.UK Search Popular on GOV.UK * Moving to the UK from Ukraine * Coronavirus (COVID-19) * Find a job * Check benefits and financial support you can get * Universal Credit account: sign in 1. Home 2. Drug Safety Update Febuxostat (Adenuric): increased risk of cardiovascular death and all-cause mortality in clinical trial in patients with a history of major
A Phase I Study to Evaluate the Pharmacokinetic Drug‒Drug Interaction of HP501, Febuxostat, and Colchicine in Male Chinese Patients with Hyperuricemia. HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor that is being developed for the treatment of hyperuricemia and gout. The primary aim of the present study was to study the pharmacokinetic drug‒drug interactions (DDIs ) of HP501, febuxostat, and colchicine in hyperuricemic patients. Hyperuricemic patients were randomly divided into group A, receiving HP501 40 mg once daily on days 1 and 4-10, and group B, receiving febuxostat 40 mg once daily on day 1 and HP501 40 mg plus febuxostat 40 mg on days 4-10. All patients received 0.5 mg colchicine once daily from day 4 to 12. Blood samples were collected for measurement
Febuxostat and renal outcomes: post-hoc analysis of a randomized trial. Effect of urate-lowering on renal outcomes in patients at high-risk for cardiovascular disease with hyperuricemia without gout is not known. We conducted a post hoc analysis of a randomized trial (Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy [FREED]). The FREED trial enrolled 1070 asymptomatic , hyperuricemic elderly patients with at least one risk factor for cardiovascular disease, divided into febuxostat (n = 537) and non-febuxostat (n = 533) groups. We compared the effect of these treatments on renal outcomes including 40% decline in estimated glomerular filtration rate, new onset of microalbuminuria and development or worsening macroalbuminuria. The relative risk of developing or worsening
Renoprotective effect of febuxostat on contrast-induced acute kidney injury in chronic kidney disease patients stage 3: randomized controlled trial. Contrast-induced acute kidney injury (CI-AKI) is known to be a complication of using intravascular contrast injection. Unfortunately, it is associated with adverse outcomes such as prolonged length of hospitalization and increased burden of health care costs. So, we aimed to determine the efficacy of febuxostat in the prevention of contrast-induced acute kidney injury among patients with chronic kidney disease Stage 3 performing percutaneous coronary intervention (PCI). In a randomized controlled trial we enrolled 120 CKD stage 3 Patients with acute coronary syndrome referred to the cardiology department Ain-Shams University hospital
A Drug-Drug Interaction Study of a Novel Selective Urate Reabsorption Inhibitor, SHR4640, and Xanthine Oxidase Inhibitor, Febuxostat, in Patients With Primary Hyperuricemia. SHR4640 is a novel, selective urate reabsorption inhibitor. As the mode of action of SHR4640 differs from that of a xanthine oxidase inhibitor, such as febuxostat, coadministration of these drugs may be a treatment option for patients with primary hyperuricemia. We assessed the potential drug-drug interaction between SHR4640 and febuxostat. In this single-center, open-label, randomized, drug-drug interaction study, subjects received 80 mg febuxostat or 10 mg SHR4640 alone daily in the first week, whereas during the second week a combination of SHR4640 and febuxostat was administered daily to all subjects. Plasma
Effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein, an oxidative stress marker: A subanalysis of the PRIZE study. Febuxostat is a selective xanthine oxidase inhibitor that reportedly exhibits antioxidant properties. We previously performed a multicentre, randomized controlled (PRIZE) study for vascular evaluation under uric acid (UA) control by febuxostat to investigate the progression of carotid lesions in asymptomatic hyperuricemic patients with carotid atherosclerosis for 2 years. The current subanalysis of the PRIZE study aimed to assess the effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker. We recruited 383 patients (febuxostat group, n = 200; control group, n = 183) from the PRIZE
Effects of febuxostat on markers of endothelial dysfunction and renal progression in patients with chronic kidney disease. Hyperuricemia relates to chronic kidney disease (CKD) progression and impaired endothelial function. Febuxostat is potent and effective for decreasing serum uric acid levels. Information for the effect of febuxostat treatment on markers of endothelial dysfunction and renal injury among patients with CKD remains limited. A total of 84 patients with CKD stages III-IV with asymptomatic hyperuricemia were randomly assigned to either the febuxostat (40 mg/day, N = 42) or the matching control (N = 42) group for 8 weeks. Serum asymmetric dimethylarginine (ADMA), estimated glomerular filtration rate (eGFR), urine albumin, high sensitivity C-reactive protein (hs-CRP), ankle