FDA Removes Boxed Warning for Amputation Risk From Canagliflozin

August 27, 2020

The removal of the boxed warning from canagliflozin was based on the FDA’s review of new data from 3 clinical trials.

Based on a review of latest data stemming from 3 clinical trials, the FDA has removed the boxed warning concerning amputation risk from the diabetes drug canagliflozin (Invokana, Invokamet, Invokamet XR) prescribing information.

Canagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that lowers blood sugar by causing the kidneys to remove sugar from the body through the urine. The drug was initially approved for use in conjunction with diet and exercise to lower blood sugar in adults with type 2 diabetes (T2D).

The agency’s requirement of the boxed warning in 2017 was based on its assessment that the risk of amputations was substantial compared with the potential benefit of canagliflozin.

More recent clinical trials have shown significant benefits to the heart and kidneys. In 2018, canagliflozin was approved by the FDA for its potential to reduce the risk of major heart-related events, including heart attack, stroke, or deaths in patients with T2D who also have identified heart disease. In 2019, canagliflozin was approved to reduce the risk of end-stage kidney disease, worsening kidney function, heart-related death, and hospitalization due to heart failure in some patients with T2D and diabetic kidney disease.

In light of these results, as well as safety information stemming from new clinical trials that demonstrated that the risk of amputation is lower than previously described, the FDA’s review concluded that the boxed warning should be removed. Because the risk of amputation still remains elevated with the use of canagliflozin, it is described in the warning and precautions section of the drug’s prescribing information.

The FDA urges health care professionals and patients to report side effects from canagliflozin to the FDA MedWatch program by contacting the FDA at druginfo@fda.hhs.gov.

Reference:

  1. FDA removes Boxed Warning about risk of leg and foot amputations for the diabetes medicine canaglifozin (Invokana, Invokamet, Invokamet XR). News Release. FDA; August 26, 2020. Accessed August 27, 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-removes-boxed-warning-about-risk-leg-and-foot-amputations-diabetes-medicine-canagliflozin.