Based on new data from two large clinical trials, the FDA has concluded that the type-2 diabetes medicine canagliflozin (Janssen’s Invokana [canagliflozin], Invokamet [canagliflozin/metformin hydrochloride], and Invokamet XR [extended-release canagliflozin/metformin hydrochloride]) causes an increased risk of leg and foot amputations. The agency is requiring new warnings, including a prominent “boxed warning,” to be added to the canagliflozin drug labels to describe this risk.
The FDA advised patients taking canagliflozin to notify their health care professionals right away if they develop new pain or tenderness, sores or ulcers, or infections in the legs or feet.
Health care professionals should, before starting a patient on a canagliflozin regimen, consider factors that may predispose patients to the need for amputations, the agency wrote in a “Drug Safety Communication.” These factors include a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. The FDA advised health care providers to monitor patients receiving canagliflozin for the signs and symptoms described above and to discontinue canagliflozin if these complications occur.
Untreated, type-2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. Canagliflozin is a prescription medicine used with diet and exercise to lower blood sugar in adults with type-2 diabetes. It belongs to a class of drugs called sodium-glucose cotransporter-2 inhibitors. Canagliflozin lowers blood sugar by causing the kidneys to remove sugar from the body through the urine.
Final results from two clinical trials—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) studies—showed that leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with placebo. The CANVAS trial showed that, over a year’s time, the risk of amputation for patients in the trial were equivalent to:
The CANVAS-R trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to:
Amputations of the toe and middle of the foot were the most common; however, amputations involving the leg, below and above the knee, also occurred. Some patients had more than one amputation, some involving both limbs.
Source: FDA; May 16, 2017.