Allopurinol: Intravenous Use for Prevention and Treatment of Hyperuricemia

2000 ◽  
Vol 18 (8) ◽  
pp. 1758-1763 ◽  
Author(s):  
Richard V. Smalley ◽  
Al Guaspari ◽  
Sandra Haase-Statz ◽  
Susan A. Anderson ◽  
Donna Cederberg ◽  
...  
Keyword(s):  
Uric Acid ◽  
Tumor Lysis Syndrome ◽  
Elevated Serum ◽  
Oral Intake ◽  
The United States ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
Time Period ◽  
Patients At Risk ◽  
Uric Acid Nephropathy

PURPOSE: To tabulate data obtained over a 21-year period to determine the efficacy and safety of an intravenous (IV) allopurinol preparation. PATIENTS AND METHODS: IV allopurinol was provided on a compassionate plea basis to patients of any age in whom xanthine oxidase inhibitor therapy was indicated as an adjunct to chemotherapy and for whom oral intake was restricted. Three hundred twenty-seven investigators at multiple hospitals in the United States treated 1,172 patients with IV allopurinol. The vast majority of these patients had a malignancy and were in danger of developing tumor lysis syndrome (TLS) and subsequent acute uric acid nephropathy (AUAN) and were unable to take oral allopurinol. Data referable to the time period of IV allopurinol administration were collected, collated, and analyzed retrospectively. There was no randomization. RESULTS: In patients initiating treatment for an elevated serum uric acid (SUA), the SUA normalized or improved in 87% of adult patients and normalized or improved in 95% of pediatric patients. IV allopurinol, administered prophylactically to patients at high risk of developing hyperuricemia and TLS, prevented an increase in SUA levels in 93% of adults and 92% of children. Toxicities caused by IV allopurinol were minimal and consisted of 10 instances of mild to moderate skin or allergic reactions. CONCLUSION: IV allopurinol is as efficacious and safe as oral allopurinol and will be of significant benefit to patients at risk of TLS and AUAN and unable to take oral medication.

A retrospective analysis of tumor lysis syndrome management in a quaternary care hospital

2019 ◽  
Vol 26 (2) ◽  
pp. 338-344
Author(s):  
Stephen Eng ◽  
Chung-Shien Lee ◽  
Seungjun Ahn ◽  
Amy Sharma
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Phosphate Binder ◽  
Tumor Lysis Syndrome ◽  
Oxidase Inhibitor ◽  
Care Hospital ◽  
Xanthine Oxidase Inhibitor ◽  
Tumor Lysis ◽  
Significant Difference ◽  
Order Set

Purpose Due to an increased use of rasburicase, the study’s purpose was to evaluate both the management of tumor lysis syndrome and the utilization of rasburicase in the hospital system. Additionally, the efficacy of flat dose rasburicase in lowering uric acid levels was evaluated. Based on the study’s findings, the investigators will evaluate the usefulness of implementing a tumor lysis syndrome order set. Methods This study evaluated patients from January 2013 through December 2016 for the rasburicase dose and the tumor lysis syndrome therapy administered. Results Overall, 251 patients were included: prophylactic rasburicase group (n = 125) vs. treatment rasburicase group (n = 126) and of rasburicase 3 mg (R3) group (n = 168) vs. 6 mg (R6) group (n = 83). The prophylactic rasburicase vs. treatment rasburicase group had a significantly lower rate of receiving a xanthine oxidase inhibitor (48.0% vs. 64.3%, p = 0.009), a phosphate binder (6.4% vs. 17.5%, p = 0.007) and an additional dose of rasburicase (20.8% vs. 41.3%, p = 0.001). Intravenous hydration was neither significantly different between the rasburicase groups (p = 0.399) nor between the two rasburicase dosing groups (p = 0.874). Between the rasburicase dosing groups, there was no significant difference in the rate of receiving a xanthine oxidase inhibitor (p = 0.521) or a phosphate binder (p = 0.390). R6 patients had a significantly greater reduction in uric acid change compared to R3 patients (median = −7.9 (−10.1, −5.5) vs. −4.3 (−6.0, −2.7), p < 0.0001). There was no significant difference in uric acid change between the prophylactic rasburicase and treatment rasburicase groups (p = 0.875). Conclusion The study’s findings justified the need to implement a tumor lysis syndrome order set. In the study population, utilizing a flat dosing method was effective for hyperuricemia.

HYPERURICEMIA IN NEOPLASTIC DISEASE IN CHILDREN: PREVENTION WITH ALLOPURINOL, A XANTHINE OXIDASE INHIBITOR

PEDIATRICS ◽  
1968 ◽  
Vol 41 (1) ◽  
pp. 52-56
Author(s):  
Irwin H. Krakoff ◽  
M. Lois Murphy
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Skin Rash ◽  
Oxidase Inhibitor ◽  
Previous Experience ◽  
Neoplastic Disease ◽  
Xanthine Oxidase Inhibitor ◽  
Neoplastic Diseases ◽  
Occasional Occurrence ◽  
Uric Acid Nephropathy

Allopurinol [4-hydroxypyrazolo (3,4-d)-pyrimidine] was used in the treatment or prevention of hyperuricemia in 21 children with various neoplastic diseases in whom there was severe hyperuricemia or in whom it might have been expected as a result of the anti-neoplastic therapy to be employed. Allopurinol was effective in reducing hyperuricemia and in preventing the hazard of uric acid nephropathy in each patient. Previous experience with such patients had been characterized by the frequent occurrence of hyperuricemia and uric acid nephropathy. Allopurinol has produced no toxicity, except for the occasional occurrence of a mild skin rash. It is considered a useful agent in the treatment or prevention of uric acid nephropathy in children with leukemia and lymphoma.

scholarly journals Metabolic and cardiovascular effects of chronic mild hyperuricemia in rodents

2018 ◽  
Vol 66 (7) ◽  
pp. 1037-1044
Author(s):  
Sun K Park ◽  
Tara R Rosenthal ◽  
Jessica S Williams ◽  
John M Shelton ◽  
Masaya Takahashi ◽  
...  
Keyword(s):  
Uric Acid ◽  
Glucose Tolerance ◽  
Serum Uric Acid ◽  
Glucose Intolerance ◽  
Fasting Glucose ◽  
Elevated Serum ◽  
Cardiovascular Effects ◽  
Oxidase Inhibitor ◽  
Sprague Dawley ◽  
Xanthine Oxidase Inhibitor

Mildly elevated serum uric acid levels are common in people with metabolic syndrome and type 2 diabetes mellitus (T2DM), but whether elevated uric acid has a causal role in the pathogenesis of diabetes remains uncertain. We tested whether chronic mild hyperuricemia in rodents under controlled laboratory conditions can cause glucose intolerance in otherwise healthy animals, or whether it can worsen glucometabolic control in animals that are genetically predisposed to T2DM. We used an established model of experimental hyperuricemia in rodents with potassium oxonate dietary supplementation, which led to sustained, approximately two-fold elevation of uric acid compared with control animals. We also reversed the hyperuricemic effect of oxonate in some animals by treatment with a xanthine oxidase inhibitor. Manipulation of serum uric acid levels in Sprague-Dawley rats for up to 18 weeks did not affect fasting glucose and glucose tolerance. Blood pressure was also not affected by hyperuricemia in rats fed a Western-type diet. We next sought to determine whether uric acid may aggravate or accelerate the onset of glucometabolic abnormalities in rats already predisposed to T2DM. Chronic oxonate treatment in Zucker diabetic fatty (ZDF) and lean control rats for up to 6 weeks did not affect fasting glucose, insulin, and glucose tolerance in ZDF rats. Taken together, these findings indicate that elevated uric acid does not directly contribute to the pathogenesis of glucose intolerance and T2DM in rodents.

Simultaneous Monitoring of Febuxostat and Uric Acid in Human Serum Samples Using the Direct Square-Wave Voltammetric Method

2019 ◽  
Vol 15 (6) ◽  
pp. 678-684
Author(s):  
Biljana Nigović ◽  
Jakov Vlak
Keyword(s):  
Uric Acid ◽  
Human Serum ◽  
Oxidase Inhibitor ◽  
Serum Samples ◽  
Boron Doped Diamond ◽  
Fast Analysis ◽  
Xanthine Oxidase Inhibitor ◽  
Voltammetric Method ◽  
Square Wave ◽  
Human Serum Samples

Background: High uric acid serum level, hyperuricemia, is now associated with many diseases such as gout, chronic kidney disease, hypertension, coronary artery disease and diabetes. Febuxostat is a novel selective xanthine oxidase inhibitor approved for the treatment of hyperuricemia. Objective: The aim of this study was to develop a first analytical method for the simultaneous determination of febuxostat and uric acid. Methods: An unmodified boron-doped diamond electrode provided concurrent quantitation of drug at low levels and uric acid, which has clinical significance in the diagnosis and therapy of hyperuricemia, at relatively high concentrations. The direct square-wave voltammetric method was applied to the analysis of both analytes in human serum samples. Results: Under the optimized conditions, the linear response of peak current on febuxostat concentration was achieved in the range from 7.5 × 10-7 to 3 × 10-5 M, while uric acid showed two linear ranges of 5 × 10-6 - 5 × 10-5 M and 5 × 10-5 - 2 × 10-4 M. The method was successfully utilised for quantification of both analytes in human serum samples. Good recoveries were obtained without interference from common inorganic cations and anions as well as glucose, dopamine, ascorbic and folic acids at concentrations expected in physiological conditions. Conclusion: The great benefits of developed method are fast analysis (only 7.5 s for run), low cost and simplicity of performance.

Allopurinol and Loss of Consciousness in a 78-old Year Man Suffering from Gout

2020 ◽  
Vol 20 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Mahnaz Arian ◽  
Mina AkbariRad ◽  
Ahmad Bagheri Moghaddam ◽  
Abdollah Firoozi ◽  
Mohammad Jami
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Kidney Stones ◽  
Oxidase Inhibitor ◽  
Loss Of Consciousness ◽  
Drug Induced ◽  
Xanthine Oxidase Inhibitor ◽  
Case Presentation ◽  
Maculopapular Rashes ◽  
Reduced State

: Allopurinol is an FDA -Approved xanthine oxidase inhibitor, which is effective in the treatment of gout, hyperuricemia and uremic kidney stones in patients with an increased level of uric acid excretion. Xanthine oxidase acts by converting hypoxanthine and xanthine into uric acid, and therefore its inhibition results in decreased production of uric acid. The most common side effects of this medication are as follows: maculopapular rashes, hives, itching, headache, dizziness, abnormal hair loss, fever and hypersensitivity reaction. Case Presentation: This report represents a case of drug-induced meningitis of a senile man who ended up in the ICU due to the remarkably reduced state of consciousness.

Fluorometric determination of uric acid in bovine milk

2010 ◽  
Vol 77 (4) ◽  
pp. 438-444 ◽  
Author(s):  
Torben Larsen ◽  
Kasey M Moyes
Keyword(s):  
Heat Treatment ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Bovine Milk ◽  
Oxidase Inhibitor ◽  
Enzymatic Oxidation ◽  
Fast Method ◽  
Xanthine Oxidase Inhibitor ◽  
Milk Samples

The primary objective of this study is to validate a new fast method for determination of uric acid in milk. The method is based on an enzymatic-fluorometric technique that requires minimal pre-treatment of milk samples. The present determination of uric acid is based on the enzymatic oxidation of uric acid to 5-hydroxyisourate via uricase where the liberated hydrogen peroxide reacts with 10-acetyl-3,7-dihydroxyphenoxazine via peroxidase and the fluorescent product, resorufin, is measured fluorometrically. Fresh composite milk samples (n=1,072) were collected from both Jersey (n=38) and Danish Holstein (n=106) cows from one local herd. The average inter- and intra-assay variations were 7·1% and 3·0%, respectively. Percent recovery averaged 103·4, 107·0 and 107·5% for samples spiked with 20, 40 or 60 μmof standard, respectively, with a correlation (r=0·98;P<0·001) observed between the observed and expected uric acid concentrations. A positive correlation (r=0·96;P<0·001) was observed between uric acid concentrations using the present method and a reference assay. Storage at 4°C for 24 h resulted in lower (P<0·01) uric acid concentrations in milk when compared with no storage or samples stored at −18°C for 24 h. Addition of either allopurinol (a xanthine oxidase inhibitor) or dimethylsulfoxide (a solvent for allopurinol) did not affect milk uric acid concentrations (P=0·96) and may indicate that heat treatment before storage and analysis was sufficient to degrade xanthine oxidase activity in milk. No relationship was observed between milk uric acid and milk yield and milk components. Authors recommend a single heat treatment (82°C for 10 min) followed by either an immediate analysis of fresh milk samples or storage at −18°C until further analysis.

scholarly journals Association Between Kidney Function Decline and Baseline TNFR Levels or Change Ratio in TNFR by Febuxostat Chiefly in Non-diabetic CKD Patients With Asymptomatic Hyperuricemia

2021 ◽  
Vol 8 ◽  
Author(s):  
Tomohito Gohda ◽  
Naotake Yanagisawa ◽  
Maki Murakoshi ◽  
Seiji Ueda ◽  
Yuji Nishizaki ◽  
...  
Keyword(s):  
Uric Acid ◽  
Strong Predictor ◽  
Sglt2 Inhibitor ◽  
Oxidase Inhibitor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Xanthine Oxidase Inhibitor ◽  
Early Change ◽  
Ckd Stage ◽  
Patients With Diabetes ◽  
Egfr Decline

Background: The levels of circulating tumor necrosis factor receptor (TNFR) 1 and 2 help predict the future decline of estimated glomerular filtration rate (eGFR) chiefly in patients with diabetes. It has been recently reported that the change ratio in TNFR1 by SGLT2 inhibitor treatment is also related with future GFR decline in patients with diabetes. The aims of this study are to investigate the association between baseline TNFR levels and early change in TNFR levels by the non-purine selective xanthine oxidase inhibitor, febuxostat, and future eGFR decline chiefly in chronic kidney disease (CKD) patients without diabetes.Methods: We conducted a post-hoc analysis of the FEATHER study on patients with asymptomatic hyperuricemia and CKD stage 3, who were randomly assigned febuxostat 40 mg/day or matched placebo. This analysis included 426 patients in whom baseline stored samples were available. Serum TNFR levels at baseline were measured using enzyme-linked immunosorbent assay. Those levels were also measured using 12-week stored samples from 197 randomly selected patients.Results: Compared with placebo, short-term febuxostat treatment significantly decreased the median percent change from baseline in serum uric acid (−45.05, 95% CI −48.90 to −41.24 mg/dL), TNFR1 (1.10, 95% CI−2.25 to 4.40), and TNFR2 (1.66, 95% CI −1.72 to 4.93), but not TNFR levels. Over a median follow-up of 105 weeks, 30 patients (7.0%) experienced 30% eGFR decline from baseline. In the Cox multivariate model, high levels of baseline TNFR predicted a 30% eGFR decline, even after adjusting for age, sex, systolic blood pressure, high sensitivity C-reactive protein, uric acid, and presence or absence of febuxostat treatment and diabetes, in addition to baseline albumin to creatinine ratio and eGFR.Conclusion: Early change in circulating TNFR levels failed to predict future eGFR decline; however, regardless of febuxostat treatment, the elevated baseline level of TNFR was a strong predictor of 30% eGFR decline even in chiefly non-diabetic CKD patients with asymptomatic hyperuricemia.

Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review

2008 ◽  
Vol 26 (16) ◽  
pp. 2767-2778 ◽  
Author(s):  
Bertrand Coiffier ◽  
Arnold Altman ◽  
Ching-Hon Pui ◽  
Anas Younes ◽  
Mitchell S. Cairo
Keyword(s):  
At Risk ◽  
High Risk ◽  
Tumor Lysis Syndrome ◽  
The United States ◽  
Standards Of Care ◽  
Close Monitoring ◽  
Tumor Lysis ◽  
High Risk Patients ◽  
Patients At Risk ◽  
Risk Patients

PurposeTumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS.MethodsA panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used.ResultsNew guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involves similar recommendations, with the addition of aggressive hydration and diuresis, plus allopurinol or rasburicase for hyperuricemia. Alkalinization is not recommended. Although guidelines for rasburicase use in adults are provided, this agent is currently only approved for use in pediatric patients in the United States.ConclusionThe potential severity of complications resulting from TLS requires measures for prevention in high-risk patients and prompts treatment in the event that symptoms arise. Recognition of risk factors, monitoring of at-risk patients, and appropriate interventions are the key to preventing or managing TLS. These guidelines should assist in the prevention of TLS and improve the management of patients with established TLS.

scholarly journals The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis: Suppressive Effects of Febuxostat

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 929
Author(s):  
Mohannad Ashtar ◽  
Hirofumi Tenshin ◽  
Jumpei Teramachi ◽  
Ariunzaya Bat-Erdene ◽  
Masahiro Hiasa ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Tumor Lysis Syndrome ◽  
Oxidase Inhibitor ◽  
Ros Generation ◽  
Ros Production ◽  
Xanthine Oxidase Inhibitor ◽  
Ovariectomized Mice ◽  
Bone Damage ◽  
Anticancer Treatment

Receptor activator of NF-κB ligand (RANKL), a critical mediator of osteoclastogenesis, is upregulated in multiple myeloma (MM). The xanthine oxidase inhibitor febuxostat, clinically used for prevention of tumor lysis syndrome, has been demonstrated to effectively inhibit not only the generation of uric acid but also the formation of reactive oxygen species (ROS). ROS has been demonstrated to mediate RANKL-mediated osteoclastogenesis. In the present study, we therefore explored the role of cancer-treatment-induced ROS in RANKL-mediated osteoclastogenesis and the suppressive effects of febuxostat on ROS generation and osteoclastogenesis. RANKL dose-dependently induced ROS production in RAW264.7 preosteoclastic cells; however, febuxostat inhibited the RANKL-induced ROS production and osteoclast (OC) formation. Interestingly, doxorubicin (Dox) further enhanced RANKL-induced osteoclastogenesis through upregulation of ROS production, which was mostly abolished by addition of febuxostat. Febuxostat also inhibited osteoclastogenesis enhanced in cocultures of bone marrow cells with MM cells. Importantly, febuxostat rather suppressed MM cell viability and did not compromise Dox’s anti-MM activity. In addition, febuxostat was able to alleviate pathological osteoclastic activity and bone loss in ovariectomized mice. Collectively, these results suggest that excessive ROS production by aberrant RANKL overexpression and/or anticancer treatment disadvantageously impacts bone, and that febuxostat can prevent the ROS-mediated osteoclastic bone damage.

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