invokana

The popular type 2 diabetes drug canagliflozin, which goes by brand names Invokana, Invokamet and Invokamet XR, causes an increased risk of leg and foot amputations, according to a safety announcement from the U.S. Food and Drug Administration (FDA) last week.

The FDA initially released a safety alert raising the possibility of the increased risk of Invokana a year ago but finally concluded that the risk is real and notable.

All medicines containing canagliflozin will now require the agency’s most prominent “boxed warning” to be added to the label, warning consumers of the increased risk of amputation.

Canagliflozin is in a class of drugs called sodium-glucose cotransporter-2 (SGLT2) inhibitors, which helps the kidneys lower glucose levels by removing it from the body in the urine. Invokana was the first in the new class of drugs and was approved by the FDA for use in the United States in 2013.

The agency came to the conclusion after analyzing two large clinical trials that showed leg and foot amputations occurred about twice as often in patients taking canagliflozin than in those taking a placebo. Both trials looked at patients over a year’s time.

“Amputations of the toe and middle of the foot were the most common; however, amputations involving the leg, below and above the knee, also occurred,” the FDA said in its announcement. “Some patients had more than one amputation, some involving both limbs.”

Invokana Faces Lawsuits Over Kidney Damage

The amputation risk warning is just the latest in a string of risks associated with the drug currently manufactured by Johnson & Johnson. In June 2016, the FDA strengthened its existing warning that canagliflozin carried the risk of acute kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA wrote at the time. “This number includes only reports submitted to FDA, so there are likely additional cases about which we are unaware.”

In about half of the cases reported to the FDA, acute kidney injuries started within a month of starting the drug and often improved after stopping.

Dozens of people have filed lawsuits against the makers of Invokana, claiming that the drug led to ketoacidosis and kidney damage.

In one case filed against Janssen Pharmaceuticals, a Johnson & Johnson subsidiary, plaintiffs claim that the company knew of the risks of kidney damage but did not do anything to stop its use or warn the public.

“To the contrary, Defendants conducted nationwide sales and marketing campaigns to promote the sale of Invokana and willfully deceived Plaintiff, her health care professionals, the medical community, and the general public as to the health risks and consequences of the use of the Invokana,” the court brief said.

In December, 55 lawsuits against Invokana were consolidated into a federal court in New Jersey by the U.S. Judicial Panel on Multidistrict Litigation.

The panel decided that all the cases had enough common factual questions to move to one courthouse to allow for coordinated pretrial hearings.

“The actions share factual questions arising from allegations that taking Invokana or Invokamet may result in patients suffering various injuries, including diabetic ketoacidosis and kidney damage,” the panel said in its December order. “The actions thus implicate numerous common issues concerning the development, manufacture, testing, regulatory history, promotion, and labeling of the drugs.”

Janssen Continues to Support Invokana Products

Even in light of the warnings of an increased risk of amputations and severe kidney damage, Janssen Pharmaceutical continues to stand by the safety of its diabetes drug.

After the December order to consolidate all Invokana cases related to kidney damage, a spokesperson for the company told Law360 that Invokana is a key drug for diabetes patients.

“Invokana is the No. 1 prescribed SGLT2 inhibitor in the United States and is an important medicine used along with diet and exercise to lower blood sugar in adults with type 2 diabetes,” spokeswoman Kaitlin Meiser said in a statement. “With real world experience that includes more than nine million prescriptions to date, we are confident in the overall safety profile of Invokana.”

Earlier this month, Johnson & Johnson issued a press release about how those taking Invokana were significantly less likely to discontinue the medication than those initiated on injectable GLP-1 receptor agonists (GLP-1 RAs).