Gout medication Uloric (febuxostat) has been linked to an increased risk of cardiac death, heart attack, stroke and heart failure in some patients who take the medication. In February of 2019, the U.S. Food and Drug Administration (FDA) issued a black box warning for Takeda’s gout medication, Uloric. The boxed statement warns of an increased risk of cardiac death associated with the medication and recommends that use of Uloric be restricted to patients who cannot take other drugs for treatment of their gout.
Uloric’s manufacturer, Takeda may be facing a number of lawsuits due to cardiac death and other serious cardiovascular side effects caused by the medication.
|Classification||xanthine oxidase inhibitor anti-gout|
|Dosage form(s)||40mg tablet
|Normal dosage||40 to 80mg daily|
Uloric Gout Use
Gout is an inflammatory condition that occurs when blood levels of uric acid are high. It affects more than 8 million people in the U.S. and causes swelling and pain of the joints, resulting in near disability for some people. Uloric (febuxostat) is a medication which is used to treat gout by reducing uric acid levels in the bloodstream by inhibiting the xanthine oxidase (XO) enzyme needed to make uric acid. Reducing uric acid levels in the bloodstream may prevent accumulation of urate crystals that are responsible for gout flare-ups.
Uloric Heart-related Death Risk
Uloric has been linked to an increased risk of heart-related death, such as fatal heart attack and stroke, in patients who take the medication. The increased risk was identified in a cardiac side effects study known as the CARES study.
The CARES study involved over 6,000 patients who were on either Uloric or another gout medication, allopurinol. The patients were followed for at least 32 months, some for as long as 6.5 years. Patients who use Uloric were shown to be 34% more likely to experience cardiac death than those who were taking allopurinol. Patients who have prior cardiac disease history may be at added risk.
Study results showed that for every 1,000 patients who took Uloric for one year, 15 heart related deaths occurred, in comparison to only 11 deaths per 1,000 patients who took allopurinol. In addition, all-cause deaths were also higher in Uloric patients, with 26 deaths per 1,000 patients, compared to allopurinol deaths of 22 per 1,00 patients.
Results indicate that the increased incidence of cardiac death occurred in all subgroups including gender, age, kidney status and other medication use. In addition, to increased cardiac death risk, patients taking Uloric were shown to be at 22% greater risk for death due to other causes and were also at increased risk for non-fatal cardiac events.
Based on the increased link to cardiovascular death, consumer watchdog, Public Citizen, has stated that if cardiovascular results had been known at the time of Uloric’s original new drug application, the medication would never have been approved for use in the U.S. in 2009. Public Citizen has called for the withdrawal of Uloric from the market. Instead, the FDA has opted to require a black box warning.
Uloric Black Box Warning
Uloric was approved in 2009 after previous attempts had failed due to serious cardiovascular risks. The 2009 approval was based on new clinical trial information which showed reduced risk. At approval, the U.S. Food and Drug Administration required additional warnings on drug labelling but also mandated that Takeda perform an additional post-approval safety study.
The CARES study was concluded in 2017, with data regarding cardiovascular risks raising serious concerns. The FDA issued a drug safety notice warning of increased rates of heart-related events which may be life-threatening or serious.
On February 21, 2019, the FDA issued another safety communication regarding the conclusion of an in-depth review of safety results. The Agency announced that a black box warning would be mandatory on all prescribing information for Uloric and required the issuance of a patient medication guide.
A black box or boxed statement warning is the most severe safety alert that is issued by the FDA. It is required to be printed at the top of the drug labeling, enclosed in a box with a thick, black border. Uloric’s black box warning states that the medication has been linked to an increased risk of cardiovascular death and all-cause death and that the medication should be reserved for use in patients who cannot take or have not responded to allopurinol for treatment of their gout.
The new medication guide for Uloric includes information about the increased cardiovascular death risk and recommends that patients inform their health care practitioner about history of heart problems or stroke.
It also advises patients to seek emergency medical assistance for symptoms that may indicate heart attack or stroke including:
- Chest pain
- Shortness of breath
- Irregular or rapid heartbeat
- Weakness or numbness on one side of body
- Speech difficulties
- Sudden headache
Uloric Lawsuit Claims
Takeda had marketed Uloric as a better treatment for gout because it was easier to prescribe than the most common medication (allopurinol) which required more titration and lab testing, and tended to leave patients without adequate gout coverage. Takeda has been accused of failing to disclose all the risks of Uloric, leaving many patients unaware of potential complications and at risk of serious cardiovascular side effects or death due to the medication.
Though Takeda is facing a number of Uloric Heart Attack and Cardiac Death Lawsuits, no settlements have been announced.
*Prior results do not guarantee or predict a similar outcome in any future matter.