Washington, DC—Based on in-depth review of results from a safety clinical trial, the FDA has concluded that there is an increased risk of death with febuxostat compared with another gout medicine, allopurinol.

Noting that the trial found an increased risk of heart-related death and death from all causes with febuxostat, marketed as Uloric, the FDA said it is updating prescribing information to require a Boxed Warning and a new patient medication guide. The agency said it also is limiting the approved use of febuxostat to specific patients who are not treated effectively or experience severe side effects with allopurinol.

Uloric was FDA-approved in 2009 to treat gout, which affects about 8.3 million adults in the United States. The drug works by lowering uric acid levels in the blood.

Patients are urged to tell a healthcare professional if they have a history of heart problems or stroke during discussion of the benefits and risks of using Uloric to treat gout. The FDA said immediate emergency medical attention should be sought and their healthcare professional alerted if patients on the drug experience:
• Chest pain
• Shortness of breath
• Rapid or irregular heartbeat
• Numbness or weakness on one side of their body
• Dizziness
• Trouble talking, or
• Sudden severe headache

The FDA urges pharmacists and other healthcare providers to counsel patients about the cardiovascular risk with Uloric and advise them to seek medical attention immediately if they experience the symptoms listed above.

“When we approved Uloric in 2009, we included a Warning and Precaution regarding possible cardiovascular events in patients treated with Uloric in the current prescribing information and required the drug manufacturer, Takeda Pharmaceuticals, to conduct a large postmarket safety clinical trial,” the FDA explained in a press release.

The trial was conducted in more than 6,000 patients with gout treated with either Uloric or allopurinol.

The results showed that, overall, febuxostat did not increase the risk of a combination of heart-related death, nondeadly heart attack, nondeadly stroke, and unstable angina—the primary outcome—but, when the outcomes were evaluated separately, patients on the drug showed an increased risk of heart-related deaths and death from all causes.

The FDA points out that, in patients treated with Uloric over a year, 15 deaths from heart-related causes were observed for every 1,000 patients versus 11 deaths from heart-related causes per 1,000 patients treated with allopurinol. The regulatory agency also reports 26 deaths from any cause per 1,000 patients treated for a year with febuxostat compared with 22 deaths per 1,000 patients treated for a year with allopurinol.

In January, a joint meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee discussed results of the safety trials.

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