A new chemical entity that inhibits uric acid production, febuxostat (Aduric®), has been recommended for inclusion in the Pharmaceutical Benefits Scheme for the treatment of chronic symptomatic gout. The 80mg tablet is intended as a once daily alternative to probenecid in patients who are contraindicated to, or intolerant of, allopurinol.
Febuxostat selectively inhibits xanthine oxidase to prevent the formation of uric acid between two and four times more potently than allopurinol. Febuxostat and its metabolites are eliminated renally and hepatically, and no dose adjustment is necessary in patients with mild or moderate impairment of the liver or kidneys.
Following initiation at 80mg daily (with or without food), the dose may be increased to 120mg if the serum uric acid remains greater than 357µmol/L after two to four weeks of therapy. Gout flares often occur initially due to mobilisation of urate from tissue deposits, which should be pre-emptively treated with NSAIDs or colchicine for up to six months.
Febuxostat has not demonstrated an effect on the QTc interval at therapeutic doses, however safety results from long-term cardiovascular outcome studies are required before it will be recommended in patients with ischemic heart disease or congestive heart failure.
Patients should be monitored closely for symptoms of allergy or hypersensitivity, and for increased plasma levels of tacrolimus following initiation of febuxostat. Uric acid levels should be monitored when potent inducers of glucuronidation are initiated or ceased, and caution is recommended in patients who are concomitantly treated with mercaptopurine or azathioprine, or in those with altered thyroid function.