Based on new data from two large clinical trials, the U.S. Food and Drug Administration (FDA) is adding a boxed warning to the type 2 diabetes medication canagliflozin (available in products - Invokana, Invokamet, Invokamet XR) due to an increased risk of leg and foot amputations.
Patients taking canagliflozin should be counseled to notify their health care professionals right away if they develop new pain or tenderness, sores or ulcers, or infections in their legs or feet.
Health care professionals should, before starting canagliflozin, consider factors that may predispose patients to the need for amputations including:
- prior amputation
- peripheral vascular disease
- neuropathy
- diabetic foot ulcers
Additionally, the FDA recommends monitoring patients receiving canagliflozin for the signs and symptoms described above and discontinuing canagliflozin if these complications occur.
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) showed that leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with placebo.
Understanding the overall risk is low, occurrence rates are listed below. The CANVAS trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to:
- 5.9 out of every 1,000 patients treated with canagliflozin
- 2.8 out of every 1,000 patients treated with placebo
The CANVAS-R trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to:
- 7.5 out of every 1,000 patients treated with canagliflozin
- 4.2 out of every 1,000 patients 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.