FDA Approves Generic Febuxostat, Despite Recent Uloric Side Effects Warning

Published on July 2, 2019 by Sandy Liebhard

The U.S. Food & Drug Administration (FDA) has apparently approved a generic version of Uloric (febuxostat), Takeda Pharmaceutical’s controversial gout drug.

India-based Alembic Pharmaceutical’s reported approval of its generic febuxostat on Tuesday, barely six months after deadly Uloric side effects resulted in the drug’s demotion to a second-line treatment for most patients.

Uloric Side Effects Flagged in Pre-Market Trials

The FDA cleared Takeda’s name-brand Uloric in 2009.

The drug is currently indicated to treat gout, an inflammatory form of arthritis caused by high uric acid levels, in patients who don’t respond well to or are unable to tolerate allopurinol (Zyloprim and Aloprim).

Takeda won FDA approval was even though pre-market clinical trials suggested certain cardiovascular events, including heart attacks, strokes, and heart-related death, occurred more frequently among patients treated with febuxostat compared to those taking allopurinol. However, the agency did stipulate that these potential Uloric side effects be listed in the “Warnings and Precautions” section of the drug’s label.

Takeda was also required to conduct a post-market study to better assess febuxostat’s cardiovascular risks.

FDA Launches Uloric Safety Review

That study was completed in November 2017.

“The preliminary results show that overall, febuxostat did not increase the risk of these combined events compared to allopurinol,” the FDA announced at the time.  “However, when the outcomes were evaluated separately, febuxostat showed an increased risk of heart-related deaths and death from all causes.”

The FDA subsequently asked an outside panel of medical advisors to review the study data. In January 2019, the committee overwhelming agreed that the potential for Uloric side effects outweighed any benefits for most patients.

By a vote of 19-2, they recommended that Uloric remain a first-line treatment for a only small number of gout patients, including those who are unable to use allopurinol, but designated a second-line treatment for all others. They also urged the FDA to highlight the post-market study findings in a black box warning on the drug’s label.

One of the dissenting panel members, however, argued that Uloric should be removed from the market entirely.

Uloric Side Effects Warning

In February, the FDA ordered the black box warning and demoted febuxostat to second-line status for most cases of gout.

According to the agency’s Drug Safety Communication, patients considering febuxostat should let their doctors know if they have a prior history of heart problems or stroke. Those currently taking the medication should seek emergency medical treatment if they experience:

• Chest pain
• Shortness of breath
• Rapid or irregular heartbeat
• Numbness or weakness on one side of your body
• Dizziness
• Trouble talking
• Sudden severe headache

Patients concerned about Uloric side effects should not stop taking febuxostat without first speaking with their doctor, as doing so could cause gout to worsen.