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Public Citizen Pressures FDA to Pull Febuxostat

Public Citizen has petitioned the U.S. Food and Drug Administration (FDA) to remove Takeda's drug febuxostat (Uloric) from the market, citing the FDA's own warnings and evidence of serious cardiovascular harms (compared with allopurinol use).

In November 2017, the FDA issued a safety alert regarding regarding febuxostat and increased risk of cardiac death (compared to allopurinol users). This was based on comparative 6000 patient safety trial wherein febuxostat showed an increased risk of cardiac-related deaths and death from all causes. (Citation source:http://bit.ly/2IuDIR5

At the initial submission, FDA did not approve febuxostat over concerns of an imbalance in CV risk with the drug (compared to allopurinol). This led to a larger safety trial, the CONFIRMS study, (Citation source: http://bit.ly/2KcB7Be) that showed contrary to other phase III results, the risk of CV events with febuxostat were the same as or lower than allopurinol. Nonetheless, the drug was saddled with warnings about possible cardiovascular events.

"Cardiovascular Events: A higher rate of cardiovascular thromboembolic events was observed in patients treated with ULORIC than allopurinol in clinical trials. Monitor for signs and symptoms of MI and stroke."

According to IMH Health, from June 30, 2014 through June 30, 2015, Uloric was the 46th most-prescribed brand-name drug in the U.S., with 1.3 million prescriptions. The company reported $1.9 billion in U.S. sales from 2012 through 2017.

In March 2018, The New England Journal of Medicine published the results of another safety study that looked at the comparative cardiovascular safety of febuxostat vs. allopurinol (Citation source: http://bit.ly/2Kp1OPb). This trial showed febuxostat to have higher all-cause mortality and cardiovascular mortality compared to allopurinol.

The FDA will review the Public Citizen petition.

 

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Rheumatologists' Comments

I would like for febuxostat to remain available for the (fairly small in reality) portion of patients who cannot tolerate or have inadequate control with allopurinol. But most of the "allopurinol failures" I see on febuxostat were uptitrated to 400 or maybe 600mg of allopurinol before switching. Febuxostat is extremely over-prescribed by non-rheumatologists in my opinion, so part of me would be glad to see it restricted for that reason.
The dosing on Febuxostat - Uloric studies were showing a dose of allopurinol 300 mg tops instead of comparison of higher doses of both. In Europe the febuxostat dosing can go higher120 mg Are there similar studies on the higher dose of both drugs?

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