Pharmacy Services Alerts
Canagliflozin Products (Invokana and Invokamet) Cause Increased Risk of Lower Limb Amputations
May 24, 2017 1:48 PM
A new black-box warning for risk of leg and foot amputations is required for canagliflozin-containing products. The FDA originally warned of a potential risk for lower limb amputations with canagliflozin on May 18, 2016 based on interim data from two trials: Canagliflozin Cardiovascular Assessment Study (CANVAS) and A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus (CANVAS-R). The risk of leg and foot amputations were doubled in those patients receiving canagliflozin. The patient population in both studies included those with type 2 diabetes with either active or a predisposition to developing cardiovascular disease. Patients in CANVAS were studied over 5.7 years, and the annualized rate of lower limb amputation was 5.9/1,000 patients for canagliflozin and 2.8/1,000 patients for placebo. The number needed to harm was 323. Similarly, CANVAS-R studied patients over 2.1 years and saw an increased annualized rate of lower limb amputation with canagliflozin (7.5/1,000 patients) when compared to placebo (4.2/1,000 patients), with a number needed to harm of 270. Increased risk was associated with both the 100 and 300 mg doses of canagliflozin. The most common amputations included the toe and middle of the foot (99/140 amputations), but more serious amputations below and above the knee and others involving the leg occurred in 41 patients. The most common events precipitating an amputation include lower limb infection (including diabetic foot ulcers), gangrene, and ischemia.
Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used to treat adults with type 2 diabetes. It is available as a single agent (Invokana) and in combination with metformin (Invokamet). Health care professionals should follow the current prescribing information for canagliflozin and monitor patients for new sores, ulcers, or infections on their lower limbs. History of amputation, neuropathy, and peripheral vascular disease predispose patients to developing amputations with canagliflozin. Patients should not stop taking canagliflozin without discussing the decision with their health care professional because uncontrolled blood sugar levels can cause serious health problems. Advise patients to contact their health care professional if they experience new pain or tenderness in their lower limbs or notice sores or ulcers on their legs or feet.
More information is available at the following links:
- FDA MedWatch Updated Alert 2017
- FDA Drug Safety Communication 2017
- FDA MedWatch Alert 2016