Welcome to the FDA Drug Safety Podcast for health care professionals from the Division of Drug Information.
On August 26, 2020, based on an FDA review of new data from three clinical trials, we have removed the Boxed Warning about amputation risk from the prescribing information for the diabetes medicine canagliflozin (brand names Invokana, Invokamet, Invokamet XR).
We required the Boxed Warning in 2017 based on our assessment that the risk of amputations was very serious in relation to the potential benefit of canagliflozin, which was initially approved to be used with diet and exercise to lower blood sugar in adults with type 2 diabetes. Subsequent FDA reviews of new clinical trial data demonstrated additional heart- and kidney-related benefits, which led to additional approved uses. Specifically, in 2018, canagliflozin was approved to reduce the risk of major heart-related events such as heart attack, stroke, or death in patients with type 2 diabetes who have known heart disease; and, in 2019, it was approved to reduce the risk of end-stage kidney disease, worsening of kidney function, heart-related death, and being hospitalized for heart failure in certain patients with type 2 diabetes and diabetic kidney disease.
Collectively, these newly identified effects of canagliflozin on heart and kidney disease show significantly enhanced benefit of this medicine. Safety information from recent clinical trials also suggests that the risk of amputation, while still increased with canagliflozin, is lower than previously described, particularly when appropriately monitored. Based upon these considerations, we have concluded that the Boxed Warning should be removed. The amputation risk with canagliflozin remains and is still described in the Warnings and Precautions section of the prescribing information.
Health care professionals and patients should continue to recognize the importance of preventative foot care and monitor for new pain, tenderness, sores, ulcers, and infections in the legs and feet. Risk factors that may predispose patients to the need for amputation should be considered when choosing antidiabetic medicines.
Canagliflozin belongs to a class of medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors and lowers blood sugar by causing the kidneys to remove sugar from the body through the urine. Untreated type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease.
Side effects involving canagliflozin should be reported to FDA’s MedWatch program at www.fda.gov/medwatch.
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