Urate-lowering therapy for gout: focus on febuxostat

Gout is a common, painful, and often debilitating rheumatologic disorder that remains one of the few arthritic conditions that can be diagnosed with certainty and cured with appropriate therapy. Allopurinol is the most frequently prescribed agent for gout in the United States. Unfortunately, most patients treated with allopurinol do not achieve target serum uric acid (sUA) levels, possibly due to a perceived intolerability to allopurinol in doses above 300 mg and the need for reduced doses in patients with renal insufficiency. Febuxostat, an orally administered, nonpurine inhibitor of xanthine oxidase, was recently approved by the U.S. Food and Drug administration for chronic management of hyperuricemia in patients with gout. Patients treated with febuxostat achieve rapid and substantial reductions in sUA levels. Compared with allopurinol-treated patients, patients receiving febuxostat 80 mg/day were more likely to achieve sUA concentrations less than 6 mg/dl. In long-term studies (up to 5 yrs), febuxostat demonstrated sustained reductions in sUA levels, nearly complete elimination of gout flares, and a frequency of adverse effects comparable to allopurinol. The most commonly reported adverse effects were liver function abnormalities, rash, nausea, and arthralgias. The recommended starting dose of febuxostat is 40 mg/day, which may be increased to 80 mg/day after 2 weeks if patients do not achieve sUA levels less than 6 mg/dl. Dosage adjustment in mild-to-moderate renal insufficiency is unnecessary; however, data are lacking on the safety of febuxostat in patients with severe renal impairment. Although more costly than allopurinol, febuxostat appears to be an acceptable alternative for the treatment of gout and hyperuricemia, and may be advantageous in patients with renal impairment, intolerance to allopurinol, or the inability to attain sUA levels less than 6 mg/dl despite adequate therapy with available agents.