Lesinurad (Zurampic) for Gout Approved in European Union

February 19, 2016

Lesinurad (Zurampic, AstraZeneca) 200 mg has been approved in the European Union for treating hyperuricemia in adults with gout in combination with a xanthine oxidase inhibitor (XOI), the manufacturer announced today.

The drug is indicated specifically for patients with gout with or without tophi who have not achieved target levels of serum uric acid with an adequate dose of an XOI.

Lesinurad helps patients with gout by inhibiting the urate transporter URAT1, responsible for most renal reabsorption of uric acid. The end result is increased excretion and decreased production of uric acid.

Headache, influenza, increased blood creatinine, and gastroesophageal reflux are the most common adverse events.

European Union approval for lesinurad came from the European Commission (EC), the European Union's executive branch. The EC followed the lead of the Committee for Medicinal Products for Human Use of the European Medicines Agency, which recommended market clearance for lesinurad in December 2015. That same month, the drug won approval for concomitant use with an XOI from the US Food and Drug Administration (FDA).

The regulatory process in the United States raised some red flags that the EC addressed in its decision. An FDA advisory committee that recommended approval of lesinurad unanimously declared it to be effective, but narrowly deemed it safe in a 7 to 6 vote with one abstention. Some committee members worried about an increase in adverse events — some cardiovascular and renal in nature — and death seen with a 400-mg dose of the drug compared with placebo. The incidence of serious adverse events was lower with the approved 200-mg dose.

In its December decision, the FDA required a postmarketing study to further evaluate the drug's renal and cardiovascular safety. The FDA also added a boxed warning to the label pointing out the risk for acute renal failure with the 400-mg dose, especially when the drug is used without an XOI. At the recommended 200-mg dose, the drug was associated with an increased incidence of serum creatinine elevations, usually reversible, and adverse reactions related to renal function, according to the label information.

The EC took similar precautions by requiring a postmarketing study of the drug's cardiovascular safety profile, mainly in patients with a history of cardiovascular disease, AstraZeneca said in a news release. The EC also called for a renal study to assess efficacy and safety in patients with creatinine clearance of 30 to 45 mL/minute.

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