People taking the type 2 diabetes drug canagliflozin, the active ingredient in the brand name drugs Invokana, Invokamet and Invokamet XR, are at an increased risk of leg and foot amputations, the Food and Drug Administration (FDA) warned based on a safety review of two large clinical trials. As a result, the safety labels of the drug will also be updated to include the agency’s most prominent warning, called a Boxed Warning, regarding this risk.
“Patients taking canagliflozin should notify your health care professionals right away if you develop new pain or tenderness, sores or ulcer, or infections in your legs or feet,” the FDA cautioned.
Health care professionals were also advised to consider factors that may predispose patients to the need for amputations before prescribing the drug, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Health care professionals were also advised to monitor patients taking canagliflozin for signs and symptoms that may lead to amputation, and to discontinue the medication if these complications occur.
Neuropathy, which can lead to amputations, is a risk factor for type 2 diabetes. Canagliflozin is a prescription medication from a class of type 2 diabetes drugs called SGLT2 inhibitors. The FDA concluded that new amputation risk warnings should be added to the medication based on two clinical trials involving adults taking canagliflozin compared to a placebo.
One trial showed that over the course of a year, 5.9 of every 1,000 patients treated with canagliflozin required amputation compared to 2.8 out of every 1,000 patients treated with a placebo. The second trial showed that over the course of a year, 7.5 out of every 1,000 patients treated with canagliflozin required amputation compared to 4.2 out of every 1,000 treated with placebo.
“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,” the FDA warned.
Invokana and Invokamet were approved in 2013 and 2014, respectively. Since then, the FDA has strengthened or added new warnings to the drug regarding adverse events. The side effects include an increased risk for serious urinary tract infections, bone fractures and bone mineral density loss, acute kidney injury, and ketoacidosis, a condition in which too much acid builds up in the blood.
Earlier this year, European drug regulators placed new amputation risk warnings on canagliflozin, as well as all other drugs in the SGLT2 inhibitor class.
Any adverse events experienced while taking this drug should be reported to the FDA MedWatch Adverse Event Reporting Program at www.FDA.gov/MedWatch/Report.htm.
FDA Safety Communication