In May 2016 the U.S. Food and Drug Administration (FDA) issued an alert after interim results from two trials suggested that canaglifllozin (Invokana) carried an increased risk of amputation.
Now, the FDA has concluded that the type 2 diabetes drug canagliflozin, manufactured by Johnson & Johnson, causes an increased risk of leg and foot amputations. The FDA is requiring new warnings, including its most prominent Boxed Warning, to be added to the canagliflozin drug labels to describe this risk.
Canagliflozin is also prescribed in combination with the diabetes medicine metformin under the brand names Invokamet and Invokamet XR. The warning applies to those drugs as well.
Canagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor and lowers blood sugar by causing the kidneys to remove sugar from the body through the urine. SGLT2s are prescribed along with diet exercise to lower blood sugar in adults with type 2 diabetes.
The decision was based on 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). In both trials, leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with placebo.
Each study lasted a year with a combined 6,000 patients receiving canagliflozin. The CANVAS trial showed that the risk of amputation for patients in the trial was equivalent to 5.9 out of every 1,000 patients treated with canagliflozin compared to 2.8 out of every 1,000 patients treated with placebo.
In the CANVAS-R trial, the risk of amputation for patients in the trial was equivalent to 7.5 out of every 1,000 patients treated with canagliflozin compared to 4.2 out of every 1,000 patients treated with placebo over the same time span.
Amputations of the toe and middle of the foot were the most common, according to the FDA’s announcement. However, amputations involving the leg, below and above the knee, also occurred. Some patients had more than one amputation, some involving both limbs.
The FDA warns health care professionals to consider factors that may predispose patients to the need for amputations before prescribing canagliflozin. These factors include a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
Any patients already receiving canagliflozin should be monitored for the signs and symptoms such as developing new pain or tenderness, sores or ulcers, or infections in your legs or feet. If these complications occur, canagliflozin should be discontinued.
Filed Under: Drug Discovery
