Febuxostat side effects may include death, including heart-related death, according to a safety announcement from the FDA.

What is Febuxostat?

Febuxostat, sold under brand name Uloric, is a medication used for the treatment of gout.

Gout is a type of arthritis caused by high levels of uric acid in the body. Although uric acid is naturally produced in the body, people with gout have too much of the substance in their body due to either an overproduction or the inability to process the substance out of the blood through the kidneys.

When there is too much uric acid in the blood, it can form urate crystals. These sharp, needle like formations can build up in the joints which can cause pain, inflammation, and swelling.

Febuxostat is a xanthine oxidase inhibitor, meaning that it decreases the level of uric acid in the body by preventing the production of the substance. This can help people with gout manage their flareups and reduce their associated symptoms including pain, swelling, redness, heat, soreness, and stiffness.

Common and Infrequent Febuxostat Side Effects

Common febuxostat side effects are usually fairly mild and may include nausea, joint pain, rash, inaccurate liver function test results, and gout flareups. However, febuxostat is also associated with more serious side effects including death.

In February 2019, the U.S. Food and Drug Administration (FDA) announced that they would be adding a boxed warning to febuxostat’s prescribing information to warn patients about the risk for heart-related death.

“The [FDA] has concluded there is an increased risk of death with [febuxostat] compared to another gout medicine, allopurinol,” the agency said in their safety announcement “This conclusion is based on our in-depth review of results from a safety clinical trial that found an increased risk of heart-related death and death from all causes with Uloric.”

Cardiology Today’s Helio says that in the summer of last year, the FDA voted that the benefits of febuxostat outweigh the risks for some groups of patients, despite the concerns associated with the drug. Because of the results, the FDA reportedly recommended a reduction of the use of the drug. 

The agency’s decision was based on the results of a post-market study conducted by Uloric manufacturer Takeda Pharmaceuticals at the behest of the FDA. The trial looked at over 6,000 gout patients who were treated with either febuxostat or allopurinol. The results of the trial reportedly looked at a combination of “heart-related death, non-deadly heart attack, non-deadly stroke, and […] unstable angina.”

Febuxostat’s History with the FDA

Cardiology Today Editorial Board Member Steven M. Nissen tells Helio that febuxostat was denied approval twice before it was eventually approved in 2009. According to to Nissen, the drug was approved after three studies were conducted. For approval, the FDA reportedly required a fourth, postmarket study to be conducted. Nissen says that this was done “very poorly,” but even with the problems of the study, the elevated risks for cardiovascular death and death from all causes for patients on febuxostat was revealed.

Helio notes that Nissen was on the FDA’s Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee, and voted that the drug’s benefits did not outweigh the risks. Reportedly, Nissen proposed a “risk evaluation and mitigation strategy,” but his ideas were rejected by the FDA. 

Although Uloric did not increase the risk of these events combined, the drug was reportedly associated with an increased risk of heart-related deaths and deaths from all causes. In the febuxostat population, there were reportedly 15 heart-related deaths for every 1,000 patients each year. In the allopurinol population, there were only 11 deaths for every 1,000 patients each year. Similar results were found when evaluating for death from all causes. In one year, there were reportedly 26 deaths for every 1,000 febuxostat patients and only 22 deaths for every 1,000 allopurinol patients.

The FDA has urged patients to tell their doctors if they have a history of heart problems such as heart attack or stroke. The agency also recommends that patients seek emergency medical care if they experience chest pain, shortness of breath, rapid or irregular heartbeat, numbness or weakness on one side of the body, dizziness, trouble talking, or a sudden severe headache.

On the other side of the coin, US Pharmacist explains that the FDA has advised pharmacists and healthcare workers to tell their patients about the risks associated with febuxostat. Particularly, these professionals are advised to stress the risk of cardiovascular problems, and to tell patients that they shod see medical attention if they experience the symptoms of cardiovascular problems.