Canagliflozin

INVOKANA (canagliflozin) is indicated: as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD). to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day. INVOKANA is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus.

SGLT2, expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Canagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RT G ), and thereby increases urinary glucose excretion (UGE). Canagliflozin increases the delivery of sodium to the distal tubule by blocking SGLT2-dependent glucose and sodium reabsorption. This is believed to increase tubuloglomerular feedback and reduce intraglomerular pressure.

Assess renal function before initiating and as clinically indicated. Assess volume status and correct volume depletion before initiating. The recommended starting dosage in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus is 100 mg orally once daily, taken before the first meal of the day to improve glycemic control. The dosage can be increased to 300 mg once daily in patients tolerating 100 mg once daily who have an eGFR of 60 mL/min/1.73 m 2 or greater and require additional glycemic control. For all other indications in adults, the recommended dosage of INVOKANA is 100 mg orally once daily. Dosage adjustments for patients with renal impairment may be required. See full prescribing information for INVOKANA dosage modifications due to drug interactions.

INVOKANA is contraindicated in patients with a serious hypersensitivity reaction to INVOKANA, such as anaphylaxis or angioedema. Serious hypersensitivity reaction to INVOKANA

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue INVOKANA if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. Lower Limb Amputation: Monitor patients for infections or ulcers of lower limb and institute appropriate treatment. Volume Depletion: May result in acute kidney injury. Before initiating INVOKANA, assess and correct volume status in patients with renal impairment, elderly patients, or patients on loop diuretics. Monitor for signs and symptoms during therapy.

The following important adverse reactions are described below and elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes and Other Ketoacidosis Lower Limb Amputation Volume Depletion Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues Hypersensitivity Reactions Bone Fracture Most common adverse reactions (5% or greater incidence): female genital mycotic infections, urinary tract infection, and increased urination.

Table 7: Clinically Significant Drug Interactions with INVOKANA UGT Enzyme Inducers Clinical Impact: UGT enzyme inducers decrease canagliflozin exposure which may reduce the effectiveness of INVOKANA. Intervention: For patients with eGFR 60 mL/min/1.73 m 2 or greater, if an inducer of UGTs is administered with INVOKANA, increase the dosage to 200 mg daily in patients currently tolerating INVOKANA 100 mg daily. The total daily dosage may be increased to 300 mg daily in patients currently tolerating INVOKANA 200 mg daily who require additional glycemic control. For patients with eGFR less than 60 mL/min/1.73 m 2, if an inducer of UGTs is administered with INVOKANA, increase the dosage to 200 mg daily in patients currently tolerating INVOKANA 100 mg daily. Consider adding another antihyperglycemic agent in patients who require additional glycemic control.

Store at 20 °C to 25 °C (68 °F to 77 °F), excursions permitted between 15 °C to 30 °C (59 °F to 86 °F).