Febuxostat is a prescription medication used to lower uric acid levels in adults with gout. Sold under the brand name Uloric, it works by blocking an enzyme called xanthine oxidase, which your body uses to produce uric acid. It is specifically approved for the long-term management of high uric acid in people who have gout, not for high uric acid on its own without gout symptoms.
How Febuxostat Works in Gout
Gout develops when uric acid builds up in your blood and forms sharp crystals in your joints, causing intense pain and swelling. Febuxostat reduces uric acid production at the source by blocking the enzyme responsible for making it. Over time, lower uric acid levels allow existing crystals to dissolve and prevent new ones from forming, which reduces the frequency and severity of gout flares.
This makes febuxostat a urate-lowering therapy, meaning it’s designed for long-term prevention rather than treating an active flare. In fact, when you first start taking it, you may temporarily experience more flares as crystals begin to break down. That’s why doctors often prescribe an anti-inflammatory medication alongside it during the first several months.
Where Febuxostat Fits Among Gout Treatments
Febuxostat is not the first medication doctors reach for. The American College of Rheumatology recommends allopurinol, an older and more widely studied drug in the same class, as the first-line urate-lowering therapy for gout. Febuxostat is typically reserved for patients who can’t tolerate allopurinol, don’t respond adequately to the highest tolerable dose of allopurinol, or have a specific reason why allopurinol isn’t appropriate.
This second-line positioning is largely driven by cardiovascular safety concerns, which emerged from a major clinical trial and led the FDA to add its strongest warning to the drug’s label in 2019.
The Cardiovascular Safety Concern
A large randomized trial called CARES compared febuxostat to allopurinol in over 6,000 gout patients who already had established heart disease. The overall rate of major cardiovascular events (heart attacks, strokes, and similar outcomes) was similar between the two drugs. However, the febuxostat group had a significantly higher rate of death from cardiovascular causes: 1.5 per 100 patient-years compared to 1.1 per 100 patient-years with allopurinol. Sudden cardiac death accounted for most of the difference, occurring in 2.7% of the febuxostat group versus 1.8% of the allopurinol group.
All-cause mortality was also higher with febuxostat (7.8% versus 6.4%), driven by the cardiovascular deaths. Based on these findings, the FDA added a boxed warning stating that febuxostat should only be used in patients who have an inadequate response to allopurinol, who are intolerant to it, or for whom allopurinol is not advisable. If you have a history of heart disease or experience a new cardiovascular event while taking febuxostat, guidelines recommend switching to a different medication.
An Advantage for People With Kidney Disease
One area where febuxostat has a meaningful advantage is in patients with chronic kidney disease, a common complication in people with gout. Allopurinol is processed through the kidneys, so its dose must be reduced as kidney function declines, which can limit how effectively it lowers uric acid. Febuxostat, by contrast, is processed primarily through the liver, so it doesn’t require the same dose restrictions for people with mild to moderate kidney impairment.
Research has also examined febuxostat in patients with more advanced kidney disease (stages 4 and 5, meaning severely reduced kidney function). A study of 63 patients in this group found that febuxostat lowered uric acid from an average of 8.96 mg/dL to 4.88 mg/dL over 12 months, a substantial drop. Kidney function remained stable during that period, and the rate of side effects was comparable to what’s seen in patients with better kidney function. This makes febuxostat particularly useful for gout patients whose kidneys can’t handle full-dose allopurinol.
Off-Label Use in Cancer Treatment
Beyond gout, febuxostat has been studied for preventing a dangerous spike in uric acid that can occur when cancer patients begin chemotherapy. As cancer cells are destroyed by treatment, they release large amounts of uric acid into the blood, a condition called tumor lysis syndrome. This can overwhelm the kidneys and become life-threatening.
The FLORENCE trial, the largest adult study in this area, randomized 346 patients with blood cancers at intermediate to high risk of tumor lysis syndrome to receive either febuxostat or allopurinol starting two days before chemotherapy. Febuxostat achieved significantly better uric acid control at a single fixed dose compared to allopurinol, and both drugs had identical rates of drug-related side effects (6.4%). Kidney function was preserved similarly in both groups. While this use is not part of the FDA-approved labeling, it represents an area where febuxostat may offer a practical benefit for certain cancer patients.
Who Should Not Take Febuxostat
Febuxostat is not recommended for people who have high uric acid without gout symptoms, a condition known as asymptomatic hyperuricemia. It also hasn’t been studied in people with high uric acid caused by other conditions, such as Lesch-Nyhan syndrome, organ transplantation, or cancer-related uric acid buildup outside of the specific tumor lysis context. Given the cardiovascular concerns, it is generally not a first choice for anyone who can safely take allopurinol, and it requires careful consideration in patients with existing heart disease.
What to Expect While Taking It
Febuxostat is taken once daily by mouth, with or without food. After starting, your doctor will check your uric acid levels periodically to see if the medication is working and may adjust the dose. The goal is typically to bring uric acid below 6.0 mg/dL, the threshold at which crystals start to dissolve.
Common side effects include liver enzyme elevations, nausea, joint pain, and rash. Liver function tests are part of routine monitoring. Because gout flares can temporarily increase when you first start any urate-lowering therapy, you should be prepared for that possibility and have a plan in place with your doctor for managing flares during the first few months of treatment.