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Febuxostat for Treatment of Chronic Gout

´╗┐Febuxostat for Treatment of Chronic Gout

Abstract and Introduction

Abstract


Purpose. The pharmacology, pharmacokinetics, clinical efficacy, and safety of febuxostat are reviewed.
Summary. Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase for the management of hyperuricemia in patients with gout. The ability of febuxostat to decrease serum uric acid production through selective inhibition of enzyme xanthine oxidase has been established in short-term Phase II and III clinical trials and long-term open-label studies. Clinical studies have revealed that febuxostat lowers serum uric acid levels more potently than allopurinol while having minimal effects on other enzymes associated with purine and pyrimide metabolism. The most frequent adverse events reported in clinical trials with febuxostat were liver function abnormalities, nausea, arthralgias, and rash. More cardiovascular thromboembolic events occurred in randomized trials in patients treated with febuxostat. Although a causal relationship has not been established, patients should be monitored for signs and symptoms of myocardial infarction and stroke. Febuxostat is available as 40- and 80-mg tablets. The recommended starting dosage is 40 mg orally once daily. If serum uric acid concentrations are not less than 6 mg/dL after two weeks, the dosage can be increased to 80 mg orally once daily. Dosage adjustments are not needed in elderly patients or patients with mild or moderate renal or hepatic impairment.
Conclusion. Febuxostat is efficacious as a second-line therapy in lowering serum uric acid levels in patients with gout. Febuxostat may be an alternative for patients with gout who are unable to take allopurinol due to hypersensitivity, intolerance, or lack of efficacy.

Introduction


Febuxostat, a chemically engineered, nonpurine, selective inhibitor of xanthine oxidase, received labeling approval in February 2009 from the Food and Drug Administration. It is the first drug marketed in 40 years for the long-term management of hyperuricemia in patients with gout.

Gout is one of the oldest metabolic diseases described, frequently categorized as a type of inflammatory arthritis. Gout is associated with the metabolic syndrome of insulin resistance, obesity, hypertension, and hypertriglyceridemia.

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