Lesinurad response

Lesinurad (brand name Zurampic) is a urate transport inhibitor used in the treatment of gout. Gout is one of the most common types of inflammatory arthritis, affecting approximately 3% of adults worldwide. It is caused by the accumulation of urate crystals in joints. The long-term management of gout includes reducing risk factors (e.g., obesity, alcohol use, diuretic use, poor renal function), and medication to lower uric acid levels. Lesinurad reduces the high level of uric acid (hyperuricemia) associated with gout. Lesinurad should only be used in combination with a xanthine oxidase inhibitor (e.g., allopurinol, febuxostat) –– the risk of acute renal failure is increased if lesinurad is used alone. The addition of lesinurad to gout treatment is reserved for patients who have failed to achieve their target uric acid level despite being treated with a xanthine oxidase inhibitor. Xanthine oxidase inhibitors reduce uric acid by inhibiting its production, whereas lesinurad reduces uric acid by blocking its reabsorption in the kidney. Lesinurad is primarily metabolized by CYP2C9 to several inactive metabolites. Individuals who lack CYP2C9 activity ("CYP2C9 poor metabolizers") have an increased exposure to lesinurad, and an increased risk of side effects. Adverse reactions of lesinurad therapy include kidney stones and other kidney problems. Lesinurad is also associated with an increased risk of cardiovascular events. The FDA-approved drug label for lesinurad states that lesinurad should be used with caution in CYP2C9 poor metabolizers, but does not provide specific dose adjustments in this group. The standard dose of lesinurad is 200 mg daily. Lesinurad is contraindicated in patients with severe impairment of kidney function (e.g., kidney transplant and hemodialysis patients) as well as individuals with tumor lysis syndrome or Lesch-Nyhan syndrome.

Medical Genetics Summaries