xanthineoxidaseinhibitors

Xanthine oxidase inhibitors are a class of medications that reduce the production of uric acid by inhibiting the enzyme xanthine oxidase, which catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid in purine metabolism. By decreasing uric acid synthesis, they lower serum urate levels and can help prevent gout flares and urate crystal deposition.

Two main agents are used clinically: allopurinol and febuxostat. Allopurinol is a structural analog of hypoxanthine; after hepatic metabolism it is converted to oxypurinol, which competitively inhibits xanthine oxidase. It is commonly prescribed for chronic gout and hyperuricemia and also used as tumor lysis prophylaxis. Febuxostat is a non-purine inhibitor that selectively binds XO and is an alternative for patients who cannot tolerate allopurinol or who do not reach target urate levels. Other inhibitors such as topiroxostat exist but are less widely used.

Adverse effects include rash, gastrointestinal upset, and liver enzyme elevations; allopurinol can cause hypersensitivity reactions, including severe cutaneous adverse reactions in some populations, and dosage adjustments are needed in kidney impairment. Febuxostat has been associated with liver function test abnormalities and, in some studies, cardiovascular mortality signals compared with allopurinol, leading to cautious use and monitoring.

Drug interactions: XO inhibitors can raise levels of thiopurines such as azathioprine and 6-mercaptopurine, so concomitant dosing reductions are recommended.

They do not treat acute gout flares and are typically started after an acute flare has subsided. They are used for long-term urate-lowering therapy and, in oncology, to prevent tumor lysis syndrome–related uric acid elevation.