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FDA Issues Warning on Deadly Gout Medication

Public Citizen News / March-April 2019

By Griet Van Acker

This article appeared in the March/April 2019 edition of Public Citizen News. Download the full edition here.

In a striking clinical trial result, the widely used gout medication febuxostat has been linked to serious health risks but has no distinctive benefits to its users. Its removal from the market by the U.S. Food and Drug Administration (FDA) should therefore be a top priority, argues Public Citizen.

Public Citizen petitioned the FDA in June 2018 to ban the medication, stating that there is “overwhelming evidence that the serious cardiovascular harms of febuxostat outweigh any purported clinical benefit.” In January, the organization testified about the drug’s dangers before a joint meeting of the FDA’s Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee.

The advisory committees met to consider a request from Takeda Pharmaceuticals America, maker of the brand name febuxostat product Uloric, to approve an update of the medication’s labeling to include the trial’s results.

Febuxostat entered the market in 2009 by the skin of its teeth; initial clinical trials testing the medication prior to FDA approval linked it to possible increased risks of serious adverse cardiovascular outcomes, including heart attack, stroke and death. The FDA rejected the medication twice over these safety concerns before approving it in 2009 on the condition that the manufacturer conduct a large, post-market randomized clinical trial to further evaluate the cardiovascular risks.

In the trial, which ran from April 2010 through May 2017, more than 6,000 gout patients were randomly assigned to once-daily doses of either febuxostat or allopurinol, a much older first-line treatment for gout. The results: The use of febuxostat increased the risk of death from cardiovascular causes compared with allopurinol. In addition, febuxostat was not better than allopurinol in preventing the symptoms and complications of gout.

What is gout?

Gout is a form of inflammatory arthritis that develops in some people who have high levels of uric acid in the blood. The acid can form needle-like crystals in a joint and cause sudden, severe episodes of pain, tenderness, redness, warmth and swelling. Common pain relievers can help during a gout attack, but more often doctors prescribe medicines that you can’t get over the counter, such as febuxostat.

“Before the FDA approved febuxostat, there was troubling evidence strongly suggesting that the medication increased the risk of serious adverse cardiovascular events and death,” said Michael Carome, director of Public Citizen’s Health Research Group. “The results of the FDA-mandated post-market trial now provide additional strong evidence of a causal link between treatment with febuxostat and an increased risk of death, particularly death from cardiovascular causes.”

Carome argued that the FDA almost certainly would not have approved febuxostat had data from the postmarket trial been available when the FDA was considering the medication in 2009. Consistent with the precautionary principal of public health, he urged the committee to recommend that the FDA grant Public Citizen’s petition and remove febuxostat from the market.

On Feb. 21, the FDA denied Public Citizen’s petition to ban febuxostat. However, the agency did approve changes to the drug’s label, including adding a black-box warning, the strongest warning that the agency can require, about the increased risk of death from cardiovascular causes compared with the older gout drug allopurinol. The agency also narrowed the approved use of the drug: The black-box warning states that febuxostat should only be used in patients who had an inadequate response to maximal doses of allopurinol and who are intolerant to allopurinol. Although the FDA allowed febuxostat to remain on the market, Public Citizen’s petition likely helped prompt the agency to require the new black-box warning on the drug’s label.