Febuxostat

FEBUXOSTAT

Febuxostat is a non-purine xanthine oxidase inhibitor that was approved by the FDA in February 2009.

Pharmacodynamics

Febuxostat is a potent and selective inhibitor of xanthine oxidase, thereby reducing the formation of xanthine and uric acid without affecting other enzymes in the purine or pyrimidine metabolic pathway. In clinical trials, febuxostat at daily dosing of 80 mg or 120 mg was more effective in lowering serum urate levels than allopurinol at a standard 300 mg daily dose. The urate-lowering effect was comparable regardless of the pathogenic cause of hyperuricemia—overproduction or underexcretion.

Indications

Febuxostat is approved at doses of 40, 80, or 120 mg the treatment of chronic hyperuricemia in gout patients. Although it appeared to be more effective then allopurinol as urate-lowering therapy, the allopurinol dosing was limited to 300 mg/d, thus not reflecting the actual dosing regimens used in clinical practice. At this time, the dose equivalence of allopurinol and febuxostat is unknown.

Adverse Effects

As with allopurinol, prophylactic treatment with colchicine or NSAIDs should be started at the beginning of therapy tovoid gout flares. The most frequent treatment-related adverse events are liver function abnormalities, diarrhea, headache, and nausea. Febuxostat appears to be well tolerated in patients with a history of allopurinol intolerance. There does not appear to be an increased risk of cardiovascular events.

Dosage

The recommended starting dose of febuxostat is 40 mg daily. Because of the concern for cardiovascular events in the original phase 3 trials, the FDA approved only 40 mg and 80 mg dosing. No dose adjustment is necessary for patients with renal impairment since it is highly metabolized into an inactive metabolite by the liver.