Uloric Side Effects: FDA Panel Addresses Cardiovascular Risks Associated with Takeda Gout Drug

Published on January 17, 2019 by Sandy Liebhard

A panel of outside advisors for the U.S. Food & Drug Administration (FDA) has finished its review of Uloric, concluding that the gout drug’s association with an increased risk of cardiovascular death and serious heart problems outweigh its benefits for most patients.

Uloric Side Effects Include Heart-Related Death

The FDA approved Takeda Pharmaceutical’s Uloric (febuxostat) in 2009.

According to the drug’s label, patients taking Uloric may face a higher risk of heart attack, stroke, and heart-related death compared to those treated with allopurino (Zyloprim and Aloprim).

Other Uloric side effects include liver toxicity, serious skin reactions, and an increased risk of gout flares when treatment begins.

When Uloric was approved, the FDA ordered Takeda to conduct an additional post-market safety study to better understand its cardiovascular risks. That study, known as the CARES trial, concluded in November 2017.

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

Panel Recommends Uloric as 2nd-Line Treatment for Most

Last Week, the FDA’s Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee met to review the CARES trial and other safety data for Uloric. At the conclusion of the meeting, the panel members voted 19 to 2 for the drug to remain a first-line treatment for a small number of gout patients, including those who can’t tolerate allopurinol.

However, they recommended that Uloric be relegated to second-line status for all others, as its risks outweigh any benefits for most patients.

Finally, the panel advised the FDA to highlight the risk of heart-related death in a black box warning – the most serious safety warning — on the Uloric label.

Although the FDA is not required to follow the recommendations of its advisory panels, it usually does So.

Others Urge FDA to Remove Uloric From Market

One of the dissenting panel members voted to remove the drug from the market, after FDA staff indicated that they were not open to a Risk Evaluation and Mitigation Strategy (REMS) for Uloric.

“It would allow the drug to be dispensed only under certain circumstances,” Steven M. Nissen, MD, MACC, told Cardiology Today. “It would be kept at a central pharmacy, and only dispensed if the doctor and patient gave informed consent that they are aware of the drug’s risks regarding CV death. The FDA was reluctant to agree to that, so I voted to remove the drug.”

Public Citizen, a highly-influential consumer advocacy group, petitioned the FDA to ban the drug last June, citing the risk of heart-related death and other Uloric side effects.

It  continues to call for a Uloric recall.

“We disagree with the panel’s vote and urge the FDA to withdraw febuxostat from the market,” Michael A. Carome, MD, director of Public Citizen’s health research group, said in a statement issued after last week’s meeting. “If such action is not taken, the agency should require the addition of a black box warning about the increased risk of cardiovascular death and modify the approved indication to limit use of the drug to patients who are not able to use allopurinol.”