FDA Approves Febuxostat for Chronic Management of Hyperuricemia in Patients With Gout

February 17, 2009 — The US Food and Drug Administration (FDA) last week approved febuxostat (Uloric), 40 mg and 80 mg, administered orally once daily, for chronic management of hyperuricemia in patients with gout, according to an announcement by Takeda Pharmaceuticals North American. This is the first new treatment option available for gout in more than 40 years.

In multiple clinical trials enrolling more than 4000 participants for up to 5 years in some studies, the xanthine oxidase inhibitor safely and effectively reduced serum uric acid levels in patients with hyperuricemia associated with gout.

CONFIRMS, the largest, pivotal, phase 3 clinical trial, showed that febuxostat 80 mg was superior to febuxostat 40 mg and allopurinol 300/200 mg at achieving the main study outcome of serum uric acid less than 6.0 mg/dL at the final visit (67%, 45%, and 42%, respectively; P < .001 for both comparisons).

The safety profile of febuxostat is well established, with liver function abnormalities, nausea, joint pain, and rash being the most frequently reported adverse reactions, occurring in at least 1% of febuxostat-treated patients, and at a rate at least 0.5% greater than placebo. Mild to moderate renal or hepatic impairment does not necessitate dose adjustments.

The mechanism of action of febuxostat is to inhibit xanthine oxidase, an enzyme that breaks down hypoxanthine (a purine base) to xanthine and then to uric acid, thereby reducing elevated levels of serum uric acid. Febuxostat is indicated for the chronic management of hyperuricemia in patients with gout, but not for the treatment of asymptomatic hyperuricemia.