February 21, 2019
5 min read

FDA adds boxed warning to febuxostat for increased mortality risk

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The FDA has added a new boxed warning to febuxostat due an increased risk of cardiovascular and all-cause mortality compared with allopurinol, according to a recent safety announcement.

Clinicians have been advised to reserve febuxostat (Uloric, Takeda) for use among patients with gout who have failed or do not otherwise tolerate maximally titrated allopurinol.

The boxed warning follows a Jan. 11 joint panel of the FDA’s Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee, which voted 19-2 with one abstention that patient populations exist in which the benefits of the gout drug febuxostat outweigh the CV risk. However, most of the panelists stated that the drug should be relegated to a second-line therapy for the treatment of hyperuricemia in patients with gout.

The panel was convened to make recommendations on the market status of febuxostat, which was approved by the FDA in 2009, after the CARES postmarket CV outcomes study. Prior to the boxed warning, the labeling for febuxostat carried a warning and precaution that a higher rate of CV events was observed in clinical trials compared with allopurinol, the only other available xanthine oxidase inhibitor.

In response to the joint panel decision, Takeda stated in a press release that it will continue to work with the FDA to ensure that febuxostat is used as safely as possible.

“Patient safety has always been our first priority at Takeda, and we appreciate that common purpose and the thoughtful discussion … with the Advisory Committee members about CARES,” Tom Harris, senior vice president and head of global regulatory affairs for Takeda, said in the release. “We have studied the safety of Uloric for more than 15 years, and remain confident in Uloric as an important option for the chronic management of hyperuricemia in gout. We look forward to additional discussions with the FDA regarding these CARES data.”

Public Citizen called for the drug’s removal from the market, first in a June petition and then in a statement from Michael A. Carome, MD, director of its health research group, delivered at the panel meeting.

“We disagree with the panel’s vote and urge the FDA to withdraw febuxostat from the market,” Carome told Healio Rheumatology. “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.” – by Robert Stott

Disclosure: Carome reports no relevant financial disclosures.