The elevated heart attack risk associated with the gout medication Uloric (febuxostat) has led to FDA removal of its status as a first-line treatment. Japan-based drugmaker Takeda Pharmaceuticals received the bad news last month after the FDA completed an analysis of postmarketing data and determined that Uloric does carry an elevated danger of fatal cardiac events.

The FDA is now requiring that package labeling carry a black box warning to that effect, and has limited use of the medication to patients who either do not respond to or are able to tolerate Zyloprim (allopurinol).

A Brief History of Uloric

Uloric is a compound discovered by Japanese biochemists in 1998. It was approved by the European Medicines Agency in April of 2008; FDA approval in the U.S. came the following year, but only after two previous applications, filed in 2005 and 2006, had been rejected. Those earlier denials were the result of cardiovascular issues that came up during the clinical trials.

When the FDA finally did grant approval in February of 2009, it was on the condition that Takeda do an extensive postmarketing safety study. The recent results of that study confirmed the heart attack danger, costing Uloric its first-line treatment status and earning it a black box warning.

Heart Attack Danger and More

Uloric is used for the treatment of hyperuricemia, a condition in which the blood contains abnormally high levels of uric acid. This usually caused by renal dysfunction, when the kidneys are unable to remove uric acid from the bloodstream. The result is gout, a common form of arthritis that affects over 8 million people in the U.S. It is traditionally associated with overindulgence in rich, fatty foods, alcohol, hypertension and obesity (not surprisingly, it is said that King Henry VIII of England suffered from gout).

In addition to increased heart attack risk, side effects associated with the use of Uloric include arthralgia (severe joint pain due to cartilage loss), diarrhea, liver disorder, headaches, nausea and rash.

Despite the risk of heart attack and other side effects, the National Institute for Health and Clinical Excellence has determined that Uloric is more effective than a regular dose of Zyloprim (but not at larger doses). Nonetheless, the recent findings of Takeda’s own postmarket studies lead to a petition from the consumer advocacy organization Public Citizen, calling on the FDA to revoke Uloric’s approval and ban the drug altogether.

Is Uloric Litigation on the Horizon?

In 2010, a former Takeda employee, Dr. Helen Ge, filed a qui tam (“whistleblower”) lawsuit in which she alleged that the drugmaker deliberately withheld information on drug interactions with Uloric as well as side effects that, in addition to cardiovascular risks, include liver failure, breakdown of muscle tissue (rhabdomyolysis), hemorrhaging and even psychiatric disorders. Although that lawsuit was dismissed in 2012, she has attempted to revive the complaint.In recent years, a growing number of plaintiffs who claim injuries due to Uloric have been coming forward to file individual complaints. If enough individual lawsuits are filed, they may be consolidated into multidistrict litigation – and depending on the outcome of cases selected for trial, Takeda may be compelled to settle.