Lower-Limb Amputation: An approximately 2-fold increased risk of lower-limb amputations associated with INVOKANA® use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials evaluating patients with type 2 diabetes who had either established cardiovascular disease or were at risk for cardiovascular disease. In CANVAS, INVOKANA®-treated patients and placebo-treated patients had 5.9 and 2.8 amputations per 1000 patients per year, respectively. In CANVAS-R, INVOKANA®-treated patients and placebo-treated patients had 7.5 and 4.2 amputations per 1000 patients per year, respectively. The risk of lower-limb amputations was observed at both the 100-mg and 300-mg once-daily dosage regimens.
Amputations of the toe and midfoot (99 out of 140 patients with amputations receiving INVOKANA® in the two trials) were the most frequent; however, amputations involving the leg, below and above the knee, were also observed (41 out of 140 patients with amputations receiving INVOKANA® in the two trials). Some patients had multiple amputations, some involving both lower limbs.
Lower-limb infections, gangrene, and diabetic foot ulcers were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy.
Before initiating, consider factors in the patient history that may predispose to the need for amputations, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients about the importance of routine preventative foot care. Monitor patients for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores, or ulcers involving the lower limbs, and discontinue if these complications occur.
Acute Kidney Injury and Impairment in Renal Function: INVOKANA® causes intravascular volume contraction and can cause renal impairment. Postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, were reported; some reports involved patients younger than 65 years of age. Before initiation, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure and concomitant medications. Consider temporarily discontinuing INVOKANA® in any setting of reduced oral intake or fluid losses; monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue promptly and institute treatment.
INVOKANA® increases serum creatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes. Renal function abnormalities can occur after initiation. Renal function should be evaluated prior to initiation and periodically thereafter. Dose adjustment and more frequent renal function monitoring are recommended in patients with an eGFR <60 mL/min/1.73 m2.