European Regulators Seek Amputation Warnings for Invokana, Other SGLT2 Inhibitors

Published on February 16, 2017 by Sandy Liebhard

A panel of the European Medicines Agency (EMA) is warning that Invokana and other SGLT2 inhibitors might be associated with an increased risk of lower limb amputations. The EMAs Pharmacovigilance Risk Assessment Committee (PRAC)  has recommended new warnings be added to the prescribing information for all Type 2 diabetes medications included in this class.

PRAC announced that it was investigating a potential link between canagliflozin (the active ingredient in Invokana and Invokamet) and lower limb amputations last April, after interim data from the Canagliflozin Cardiovascular Assessment Study (CANVAS) found that such amputations occurred nearly twice as often in patients treated with canagliflozin compared to those who received a placebo. The investigation was expanded in July to include all SGLT2 inhibitors.

“An increased risk has not been seen in studies with other medicines in the same class, dapagliflozin and empagliflozin,” PRAC said in a statement dated February 10^th. “However, data available to date are limited and the risk may also apply to these other medicines.”

The U.S. Food & Drug Administration (FDA) is also investigating lower limb amputations that may be associated with Invokana and Invokamet. The agency has not yet announced the results of its investigation.

SGLT2 Inhibitor Side Effects & Litigation

Invokana was approved by the FDA in March 2013. Since then, the agency has cleared a number of other SGLT2 inhibitors to treat Type 2 diabetes, including:

• Invokamet (canagliflozin and metformin)
• Farxiga (dapagliflozin)
• Xigduo XR (dapagliflozin and metformin extended-release)
• Jardiance (empagliflozin)
• Glyxambi (empagliflozin and linagliptin)

Since their introduction, SGLT2 inhibitors have been the subject of multiple FDA safety alerts. In September 2015, for example, the agency announced that the labels for Invokana and Invokamet would be updated to include information about a possible increased risk of bone fractures. The following December, new warnings regarding diabetic ketoacidosis and serious urinary tract infections were added to the labels of all SGLT2 inhibitors. And last June, existing kidney warnings included on the labels of Invokana, Invokamet, Farxiga and Xigduo XR were strengthened after the drugs were linked to more than 100 reports of acute kidney injury.

Dozens of lawsuits have been filed in U.S. courts on behalf of individuals who suffered ketoacidosis, kidney injuries and other side effects allegedly related to treatment with SGLT2 inhibitors. Federally-filed Invokana and Invokamet lawsuits  have already been centralized in the U.S. District Court, District of New Jersey. Farxiga and Xigduo XR plaintiffs  have also requested that their cases be centralized  in the Southern District of New York, Eastern District of Pennsylvania, or Southern District of Illinois. The U.S. Judicial Panel on Multidistrict Litigation is scheduled to hear Oral Arguments on the matter during its March 30^th Hearing Session.