Febuxostat: The evidence for its use in the treatment of hyperuricemia and gout

Birmingham VA Medical Center.
Core Evidence 06/2010; 4:25-36.
Source: PubMed


Gout is a common and disabling cause of arthritis in middle-aged and elderly populations, with its main predisposing factor being hyperuricemia (serum urate > 6.8 mg/dL). Options for treatment of chronic gout until 2008 were allopurinol, a xanthine oxidase inhibitor, and the group of drugs known as uricosurics that stimulate the renal excretion of uric acid. A proportion of patients, including some with chronic kidney disease and solid organ transplantations, could not be treated with the those therapies because of intolerance, drug interactions, or adverse events. Febuxostat is a nonpurine xanthine oxidase inhibitor, recently approved in Europe and the United States for the treatment of chronic gout.
To review the clinical evidence (phase II and III studies) of the effectiveness and safety of febuxostat for treatment of hyperuricemia and gout.
Febuxostat, at doses ranging from 40 to 240 mg/day, is efficacious in reducing serum urate in patients with hyperuricemia and gout, comparing favorably with fixed doses of allopurinol in that respect. Early safety signals with respect to liver test abnormalities and cardiovascular outcomes have not been confirmed in recent large prospective trials but need to be further monitored.
Given its low cost and extensive clinical experience, allopurinol will likely remain the first-line drug for management of hyperuricemia and gout. Febuxostat may provide an important option in patients unable to use allopurinol, those with very high serum urate levels, or in the presence of refractory tophi.

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    ABSTRACT: Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than "standard dosage" allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol.
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    ABSTRACT: Purpose: To enable clinicians to initiate appropriate steps for long-term management of gout, including controlling acute exacerbations and pain and sustaining target serum uric acid (SUA) levels to control hyperuricemia as the underlying metabolic disorder. Data sources: Incorporation of pertinent rheumatology and primary care literature seeking a comprehensive overview about the disease state of gout and its symptoms, comorbidities, and impact on quality of life, with a key focus on the role of serum uric acid, evidence-based approaches to long-term management of gout, and the importance of a functioning clinician-patient relationship. Conclusions: Gout is increasingly recognized as a prevalent chronic disease state requiring appropriate long-term management while controlling for risk factors and comorbid conditions. Effective treatment options can help gout patients achieve therapeutic SUA targets to control gout flares and prevent potentially destructive disease manifestations. Patient education is an important element in achieving treatment goals and ensuring adherence. Implications for practice: Effective treatment plans for any gout patient must be guided by a long-term approach that focuses on sustained control of hyperuricemia, while providing continuous control of chronic disease. Patient education can be a key element in this process. ©2010 The Author(s) Journal compilation
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    ABSTRACT: Uric acid is the end product of purine metabolism, elevation of it can cause Gout. Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase being developed for the management of hyperuricaemia in patients with gout. Conformational analysis and geometry optimization of Febuxostat was performed according to the Hartree-Fock (HF) calculation method by Argus Lab 4.0.1 software. The minimum potential energy was found to be-80598.933 kcal/mol. It is the most feasible position for the drug to interact with the receptor.
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