FDA Says Invokana May Be Linked to Amputations

Published on May 20, 2016 by Sandy Liebhard

The U.S. Food & Drug Administration (FDA) warned this week that canagliflozin, an active ingredient in Invokana and Invokamet, may be associated with an increased risk of foot and leg amputations, especially those affecting the toes. While the agency has not concluded that such an association definitively exists, it has launched a review of the issue.

Invokana and Invokamet are both marketed by Johnson & Johnson’s Janssen Pharmaceuticals unit.  Invokana contains only canagliflozin, while Invokamet is a combination of that ingredient and metformin. Both belong to a class of Type 2 diabetes medications called SGLT2 inhibitors.

According to Drug Safety Communication issued by the FDA on May 18^th, interim safety results from an ongoing clinical trial called Canagliflozin Cardiovascular Assessment Study (CANVAS) found amputations affecting the legs and feet occurred nearly twice as often in patients treated with canagliflozin. An interim analysis showed that over a year’s time, the risks of amputation for patients in the trial were equivalent to:

• 7 out of every 1,000 patients treated with 100 mg daily of canagliflozin
• 5 out of every 1,000 patients treated with 300 mg daily of canagliflozin
• 3 out of every 1,000 patients treated with placebo

A similar increased risk was not seen among canagliflozin patients in a related study called CANVAS-R. The CANVAS trial followed patients for an average of 4.5 years to date, while those enrolled in CANVAS-R have been followed for an average of 9 months.

Invokana and the FDA

This is not the first time Invokana and Invokamet have been cited in an FDA safety communication. In May 2015, the agency launched a review of all SGLT2 inhibitors, after the drugs were linked to reports of diabetic ketoacidosis, a dangerous condition that can lead to diabetic coma and death. In December 2015, the FDA ordered the drugs’ manufacturers to add new warnings to their product labels regarding this possible complication, as well as a potential association with serious urinary tract infections that could lead to kidney complications.

A number of Invokana lawsuits have been filed in U.S. courts since the FDA announced its diabetic ketoacidosis investigation. According to a report published by The Legal Intelligencer, at least 33 claims involving Invokana and ketoacidosis or kidney damage were pending in Pennsylvania’s Philadelphia Court of Common Pleas as of May 13^th.