Febuxostat (Uloric): Xanthine oxidase inhibitor approved for chronic management of hyperuricemia in patients with gout

Febuxostat is a xanthine oxidase inhibitor that decreases serum uric acid. This agent was approved on February 13, 2009, for the chronic management of hyperuricemia in patients with gout.

Efficacy. The efficacy of febuxostat was assessed in 3 randomized, double-blind, controlled trials. In Study 1, patients were randomized to treatment with febuxostat 40 or 80 mg/d or allopurinol 200 or 300 mg/d. Patients were treated for 6 months. In Study 2, patients were randomized to treatment with febuxostat 80, 120, or 240 mg/d or allopurinol 100 or 300 mg/d. Patients were treated for 6 months. In Study 3, patients were randomized to treatment with febuxostat 80 or 120 mg/d or allopurinol 300 mg/d. Patients were treated for 1 year. Febuxostat 80 mg/d was superior to allopurinol in the proportion of patients who achieved serum uric acid <6 mg/dL at the final visit in all 3 studies (Study 1: difference between febuxostat 80 mg/d and allopurinol, 25%; 95% CI, 20%–30%; Study 2, 33%; 95% CI, 26%–42%; Study 3: 38%; 95% CI, 30%–46%). Febuxostat 40 mg/d was not superior to allopurinol (Study 1: difference between febuxostat 40 mg/d and allopurinol, 3%; 95% CI, –2% to 8%) but was as effective as allopurinol in lowering serum uric acid to <6 mg/dL.

Safety. After febuxostat therapy is initiated, an increase in gout flares may occur. Patients may be treated with concurrent prophylactic therapy (including a nonsteroidal anti-inflammatory drug [NSAID] or colchicine) to prevent these flares. In clinical trials, febuxostat-treated patients demonstrated a higher rate of cardiovascular thromboembolic events than allopurinol-treated patients. Febuxostat-treated patients have also experienced transaminase elevations >3 times the upper limit of normal (ULN) during clinical trials. The most common adverse events associated with febuxostat treatment include liver function abnormalities, nausea, arthralgia, rash, and dizziness.

Dosing. Febuxostat should be initiated at a dose of 40 mg once daily. If patients do not achieve a serum uric acid level <6 mg/dL after 2 weeks, the dose should be increased to 80 mg once daily.