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Uloric Heart Attack, Stroke & Death Risk

The U.S. Food and Drug Administration (FDA) issued a February 2019 black box warning for Uloric. The FDA has issued a black box warning about an increased risk of cardiac death in people who take gout medication, Uloric. The black box or boxed statement warning is the most serious safety alert that can be issued by the FDA.

Uloric (febuxostat)

Gout is a painful inflammatory condition caused by high blood levels of uric acid. Symptoms of gout are similar to arthritis including pain, swelling and redness in the joints. Uloric (febuxostat) is a medication used to treat gout which works by interfering with production of uric acid.

Manufacturing information

Brand NameUloric
Generic Namefebuxostat
Classificationxanthine oxidase inhibitor anti-gout
ManufacturerTakeda
Dosage form(s)40mg tablet80mg tablet
Normal dosage40 to 80mg daily

Uloric Black Box Warning

The U.S. Food and Drug Administration (FDA) issued a February 2019 black box warning for Uloric. The black box or boxed statement warning is the most serious safety alert that can be issued by the FDA.

Uloric’s black box warning indicates that use of the medication has been linked to an increased risk of cardiac death. It also recommends that Uloric be reserved for patients who have not responded to allopurinol, the most popular gout treatment or who cannot tolerate allopurinol.

The FDA also required that Takeda. Uloric’s manufacturer, create a new medication guide to provide patients with information about the risks of Uloric. In addition to general information, the medication guide informs patients of the symptoms of cardiovascular events which may be life-threatening such as stroke, heart attack or heart failure.

Patients are encouraged to seek emergency help for symptoms that indicate a serious cardiac event such as:

  • Chest pain
  • Sweating
  • Shortness of breath
  • Rapid or irregular heartbeat
  • Sudden headache
  • Dizziness
  • Numbness or weakness on one side of body
  • Speech difficulties

Uloric Cardiovascular Death Risk

Uloric was found to be linked to increased cardiac death risk in a large clinical study commissioned after the 2009 drug approval. The CARES study followed more than 6,000 patients who were taking either allopurinol or Uloric. Each patient was followed for at least 32 months, some for up to 6.5 years.

Study results showed that people who took Uloric were 34% more likely to experience cardiac death than those taking allopurinol. Uloric patients were also 22% more likely to die of any cause and had a greater risk for a non-fatal cardiac event such as heart failure, stroke or non-fatal heart attack. Increased risks associated with Uloric use occurred in all groups regardless of age, gender, kidney function or other medications taken.

A consumer protection group, Public Citizen, has called for Uloric to be recalled from the market and has said that if the cardiac risk had been known at the time of Uloric’s approval, it never would have made it to market. Based on CARES results, the FDA issued a black box warning for Uloric but has not recalled the medication.

Treatment of Gout

Gout is an inflammatory disease that affects 8.3 million Americans. It is similar to osteoarthritis and is the most common form of inflammatory arthritis in men. The most common symptom of gout is pain, swelling and stiffness in the big toe but it affects other joints as well, particularly as the disease progresses.

Gout occurs when blood levels of a substance known as uric acid are too high.  High uric acid levels lead to crystallization and urate salt deposit formation in the joint spaces. The needle-like crystals are irritating to joint tissue and urate salt deposits, known as “tophi” may become very large, both formations may cause pain, swelling, and redness in the joints. Over time, inflammation and tophi growth may lead to joint damage, tissue destruction and loss of mobility.

Treatment of gout involves:

  • Management of pain and symptoms with non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids or colchicine,
  • Treatment with medications that reduce uric acid levels in the bloodstream
  • Lifestyle changes to reduce uric acid buildup and manage symptoms such as dietary management, weight loss and alcohol avoidance

Though gout is usually a chronic disease, attacks of more severe symptoms can occur suddenly and in the middle of the night. Acute attack symptoms are usually worst at 12 to 24 hours after it starts and may take 1 – 2 weeks to recover, even with management.

Blood uric acid levels may not be high when gout attack occurs and reduction of uric acid levels may not result in immediate relief of symptoms as urate will be slowly moved out of tissues or “mobilized”.  If serum blood levels of uric acid are not elevated, a joint fluid extraction may be performed and examined for uric acid or identify other issues such as presence of bacteria or other irritants.

Not everyone with high uric acid levels or hyperuricemia has symptoms of gout. Those who are asymptomatic may require a different kind of treatment than people with gout symptoms.

Pseudogout is a condition which appears similar to gout but is not caused by uric acid. Joint irritation and inflammation in pseudogout is caused by calcium phosphate crystals rather than urate and requires different treatment.

How does Uloric Work?

Uloric works to reduce blood levels of uric acid by interfering with the xanthine oxidase enzyme used in purine metabolism. Over time, reduction in uric acid levels will help to reduce symptoms of gout.

Uloric was intended to be easier to prescribe than allopurinol, the most common anti-gout medication. Allopurinol may require careful titration to obtain appropriate uric acid levels and many patients are left with inadequate treatment. Uloric is designed to reduce uric acid levels more efficiently, however the medication has proven to cause serious complications that may be life-threatening.

Uloric use is now recommended only for patients who do not respond to allopurinol or who have been shown to be intolerant to allopurinol. This recommendation is part of the FDA’s black box warning. Uloric prescribing information also states that it is not intended to be used in people who have high uric acid levels but do not exhibit symptoms of gout.

Uloric Side Effects

Uloric may also cause side effects which are less severe or will go away with time. Some of these side effects are also common to other gout medications.

Common side effects of Uloric may include:

  • Nausea
  • Headache
  • Rash
  • Painful joints

In the beginning stages of Uloric treatment, patients may experience flares of gout symptoms. This occurs when urate is mobilized or released from tissues and may continue to be bothersome for a period of months. Gout flares after beginning new therapy may be managed with non-steroidal anti-inflammatory drug (NSAID) treatment or with colchicine. In some cases, colchicine treatment may be required as a maintenance medication.

Due to risk of cardiac death, Uloric is not recommended to be used for patients who have hyperuricemia but do not have symptoms of gout, or those who are asymptomatic.

Uloric Lawsuit

People who took Uloric and were harmed or loved ones of those who died after treatment with Uloric may be filing lawsuits against Takeda. More information about Uloric lawsuits is available here.

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