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Boxed Warning Added to Diabetes Drug

May 16, 2017

The US Food and Drug Administration (FDA) just announced that labels for the drug canagliflozin (Invokana, Invokamet, Invokamet XR) will need to include a new boxed warning.

The updated warning is based on findings from two clinical trials that found that the type 2 diabetes medicine “causes an increased risk of leg and foot amputations,” according to the safety alert.

Specifically, the trials showed that “leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with placebo….Amputations of the toe and middle of the foot were the most common.” However, some patients’ amputations involved the leg (above and below the knee), and other patients needed more than one amputation (FDA Drug Safety Communication. May 16, 2017).

The FDA recommends that providers review patient history for any predisposing factors for amputation before prescribing canaglifozin; and patients taking the medicine should report any symptoms such as “new pain or tenderness, sores or ulcers, or infections in your legs or feet” to physicians.

The two trials were the CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus).

—Amanda Del Signore

Update: Janssen has released the following statement in response to the FDA’s drug safety communication regarding Invokana:

Canagliflozin is an important treatment option for people with type 2 diabetes.  

The finding of increased risk of lower-limb amputation—primarily of the toe and forefoot—observed last year in the interim safety analysis of the CANVAS study of patients at high risk for cardiovascular events or with established CV disease, was confirmed in the final analysis of CANVAS and CANVAS-R.  The U.S. FDA shared the initial observation last May in a Drug Safety Communication, and Janssen shared it directly with Heath Care Professionals. While the incidence was low, the highest incidence of amputations across all treatments was seen in patients with prior amputation.

At Janssen, patient safety is our highest priority. We are working with FDA to include this information in the prescribing information for canagliflozin and look forward to the presentation of the full CANVAS Program results at the American Diabetes Association Scientific Sessions in June.


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