The Food and Drug Administration (FDA) has released a boxed warning that febuxostat (Uloric), a drug used to treat gout, carries a greater risk of death compared to allopurinol, another gout treatment. According to the FDA, febuxostat is associated with increased heart-related and all-cause mortality.
A boxed warning is the FDA’s most prominent.
In addition to the new warning, the FDA has also issued a new patient medication guide for the drug.
“We are also limiting the approved use of Uloric to certain patients who are not treated effectively or experience severe side effects with allopurinol,” the FDA stated.
— FDA Drug Information (@FDA_Drug_Info) February 21, 2019
Uloric: Initial Approval and Possible Cardiovascular Outcomes
The FDA first granted febuxostat approval in 2009 to treat adult patients with gout, a type of arthritis. Uloric targets uric acid levels in the blood that are built up in gout patients, which causes redness, swelling, and pain in one or more joints.
The 2009 approval included a precaution that the drug may be associated with cardiovascular events, so Takeda Pharmaceuticals, its manufacturer, was required to perform a clinical trial to determine febuxostat’s safety.
The trial included 6,190 patients with gout and cardiovascular disease who were randomized to either febuxostat or allopurinol; patients were followed for an average of 32 months. The study’s primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization.
At the time, the study concluded that “febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events,” but that all-cause and cardiovascular mortality risk was greater among febuxostat patients.
I covered febuxostat and CARES trial in Episode 14. Given CV risk signal, allo is first line for ULT for me. Flaws in trial (dropout ~50%, 85% of events off therapy, NO plbo group) limit conclusions re:safety, so I still use FEBU but discuss w/pts before starting #RWCS2019
— Mike Putman (@EBRheum) February 14, 2019
“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA noted in its announcement. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”
The FDA also acknowledged that gout treatment options are limited.
Per the FDA, patients taking febuxostat are urged to contact their doctor if they experience any of the following symptoms:
- Chest pain
- Shortness of breath
- Rapid or irregular heart beat
- Numbness or weakness on one side of your body
- Trouble talking
- Sudden severe headache
“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA stated. “Counsel patients about the cardiovascular risk with Uloric and advise them to seek medical attention immediately if they experience the symptoms listed above.”
FDAhas added a boxed warning to the label for gout drug febuxostat (Uloric) based on results of a large postmarketing safety study and AAC panel Recs. FDA concluded that there is an increased risk for death with febuxostat compared allopurinol https://t.co/v1ANA3lI0g
— Dr. John Cush (@RheumNow) February 22, 2019
New black box warning out for #gout medication febuxostat (brand name Uloric) after study shows significantly higher risk of all-cause & #heart related deaths than its alternative, allopurinol, per FDA. #SoMeDocs #medtwitter #twitternist #FOAMed #MEDed #hcsm #hcim pic.twitter.com/VgMpzoidDC
— Dana Corriel, MD (@DrCorriel) February 22, 2019