The FDA recently ordered a black box warning regarding lower extremity amputation to be added to the list of potential Invokamet and Invokana drug side effects. The black box warning will call attention to the fact that Invokamet and Invokana drug side effects have been linked to an increased rate of lower extremity amputation.

The FDA’s order was announced on May 16, 2017, with the medical director and CEO of the Minnesota Center for Obesity, Metabolism and Endocrinology and a member of the editorial board for EndocrineWebDr. J. Michael Gonzalez-Campoy stating it was not surprising the agency was requiring this black box warning for Invokamet and Invokana drug side effects. The FDA concluded patients faced a significant risk of lower extremity amputation, especially in the toes and middle of the foot.

”Based on new data from two large clinical trials, the FDA has concluded that the type 2 diabetes medicine canaglifozin (Invokana, Invokamet, Invokamet XR) causes an increased risk of leg and foot amputations. FDA is requiring new warnings, including the most prominent Boxed Warning, to be added to the canagliflozin drug labels to describe this risk,” the FDA stated.

This order is also an update to an earlier warning from the FDA in 2016, stating the agency had found higher incident reports of lower extremity amputation in patients prescribed canagliflozin based medications.

Overview of Invokamet and Invokana Drug Side Effects

The FDA issued this warning after reviewing the CANVAS (Canagliflozin Cardiovascular Assessment Study). CANVAS found that patients were twice as likely to face the possibility of lower extremity amputation. A second trial had found similar results, so it is not surprising the FDA eventually issued a black box addition to Invokamet and Invokana drug side effects.

However, according to Endocrineweb, Dr. Gonzalez-Campoy pointed out that a cause and effect was not definitely proven and that patients involved were already suffering from the effects of type-2 diabetes.

At this point, medical experts cannot explain why canagliflozin based medications may increase the risk of lower limb amputation but some believe it may be linked to how the medications are processed through the kidneys.

Canagliflozin is part of the SGLT2 inhibitor drug family, which lowers blood sugar levels by signaling the kidneys to expel excess sugar through urination.

Dr. Gonzalez-Campoy states that the treatment mechanism may cause a patient to become dehydrated, which can cause the constriction of blood vessels in the legs. If blood flow in the legs becomes constricted, foot ulcers can form and bacterial infections may develop leading to the need for lower extremity amputation.

Even though the FDA is ordering the black box warning into the Invokamet and Invokana drug side effects, patients are still at risk for lower extremity amputation. Type-2 diabetes is one of the most significant health crises in the United States, with millions of patients taking medications to manage their symptoms.

At this point in time, the FDA is advising Invokamet and Invokana patients to talk to their doctors if they notice any new pain, tenderness, sores, ulcers, or infections in their legs or feet.

In addition, patients who are at an increased risk for lower extremity amputation include those who have had a history of nerve problems, peripheral vascular disease, foot ulcers, or previous amputations.