Febuxostat (Uloric)

Trade name Uloric

Oral agent with 49% bioavailability.

99% protein bound to albumin.

Metabolism via CYP1A2, 2C8, 2C9, UGT1A1, 1A3, 1A9, 2B7

Half-life ~5-8 hours.

Excretion about 49% mostly as metabolites, 3% as unchanged drug, and via feces about 45% mostly as metabolites, and 12% as unchanged drug.

A urate lowering drug, an inhibitor of xanthine oxidase, that is indicated for use in the treatment of hyperuricemia and chronic gout.

Comparing febuxostat to allopurinol: more individuals treated with febuxostat had decreased levels of uric acid, but no difference in the amount of gout flares or the surface area of gout tophi.

It has not been shown to be clinically more efficacious or cost effective compared with allopurinol.

Recommended for people who are intolerant of allopurinol.

A non-purine selective inhibitor of xanthine oxidase, that non-competitively blocks the molybdenum pterin center which is the active site on xanthine oxidase.

Xanthine oxidase oxidizes both hypoxanthine and xanthine to uric acid.

Febuxostat inhibits xanthine oxidase, reducing production of uric acid.

Febuxostat inhibits both oxidized as well as reduced form of xanthine oxidase.

In clinical trials it is superior to allopurinol in reducing the serum uric acid levels.

Febuxostat versus Allopurinol Controlled Trial (FACT): 760 patients with gout and a serum uric acid >8.0 mg/dl were randomly assigned to receive either febuxostat 80 or 120mg or allopurinol 300mg once daily for 52 weeks.

In the above study the primary endpoint was the proportion of patients to achieve a serum uric acid concentration below 6.0 mg/dl at the last three monthly measurements: The primary endpoint was achieved in 53% of patients receiving 80 mg febuxostat, 62% of patients receiving 120mg and 21% of those receiving allopurinol.

The APEX trial was a head-to-head phase III controlled clinical trial for gout, with a total of 1072 patients with serum uric acid levels higher than 8.0 mg/dl: Patients were randomized to a once daily fixed dose of placebo; febuxostat 80mg,120mg, or 240 mg; or allopurinol 300mg or 100mg, depending on their baseline serum creatinine.

In the APEX trial : After 1 year of treatment, 82% of the patients in all febuxostat groups achieved serum uric acid levels below 6.0 mg/dl, compared with 39% of the patients in both allopurinol groups.

In the APEX trial groups with moderate renal impairment the primary endpoint was achieved by 44% receiving febuxostat 80mg, 45% receiving 120mg, and 60% receiving 240mg, compared with 0% in the allopurinol and placebo groups.

The EXCEL trial assessed the clinical efficacy and safety of febuxostat against allopurinol long-term: After the first month of treatment, nearly 80% of patients receiving either febuxostat dose achieved serum uric acid less than 6 mg/dl, compared with only 46% of subjects on allopurinol.

Uloric 40 mg tablets with treatment of hyperuricemia in patients with gout, febuxostat is recommended at 40 mg or 80 mg once daily.

No dose adjustment is necessary in patients with mild to moderate renal and hepatic impairment.[

Adverse effects include: nausea, diarrhea, arthralgia, headache, increased hepatic serum enzyme levels and rash.

Contraindicated with concomitant use of theophylline and chemotherapeutic agents, namely azathioprine and 6-mercaptopurine, because it could increase blood plasma concentrations of these drugs, and therefore their toxicity.

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