Febuxostat

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Indications :

The FDA has limited the approved use of febuxostat to patients who are unresponsive to or cannot tolerate allopurinol.
- Gout
- #todo can it be used for TLS?
A meta-analysis was performed to evaluate the efficacy and safety of febuxostat, as compared with allopurinol, as a preventive measure of TLS [49]. It included six studies that were reported between 2014 and 2017 and involved a total of 659 patients with mainly hematologic malignancy (331 treated with febuxostat and 328 treated with allopurinol). Febuxostat and allopurinol achieved a similar response rate (odds ratio [OR] 1.01, 95% CI 0.55-3.51) and TLS incidence (OR 1.01, 95% CI 0.56-1.81). Serum uric acid levels did not differ between patients treated with febuxostat and those treated with allopurinol at the second day (mean difference -0.21 mg/dL, 95% CI -1.30 to 0.88) and at the seventh day (mean difference -0.43 mg/dL, 95% CI 1.38-0.51) of treatment. Drug-related complications were similarly low between the two groups, with increased liver enzymes being the most common adverse event.

Dose adjustment is not needed in patients with mild to moderate renal impairment

Noncompetitive xanthine oxidase inhibitor.
It is not a purine base analog; because of the non-purine structure, febuxostat inhibits both reduced and oxidized forms of xanthine oxidase and has minimal effects on other enzymes involved in purine and pyrimidine metabolism

Elevated aminotransferase levels can rarely occur, and liver enzymes should be monitored.
Concomitant use with purine analogues is contraindicated.
Incidence of hypersensitivity is rarer and usually less severe than with allopurinol.
In a 2018 safety study, febuxostat users had an increased risk for cardiovascular death and all-cause mortality compared with patients receiving allopurinol. These data do not define febuxostat as raising risk compared with no treatment, and other studies have failed to support this observation; however, the results prompted the FDA to mandate a boxed warning for febuxostat regarding increased risk compared with allopurinol.
There are fewer drug-drug interactions with febuxostat than with allopurinol
Manufacturer advises against taking Thiopurines (Azathioprine and Mercaptopurine) or Mercaptopurine concurrently because concomitant administration could increase plasma concentrations of these thiopurines, resulting in severe toxicity.