APO-CANAGLIFLOZIN

, Geriatrics). 1 Special Populations). 2 CONTRAINDICATIONS • Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see

, Elderly Patients, 4 DOSAGE AND ADMINISTRATION, Geriatrics). 1 Special Populations). 2 CONTRAINDICATIONS • Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

• Patients on dialysis (see 4 DOSAGE AND ADMINISTRATION). 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions Diabetic Ketoacidosis • Clinical trial and post-market cases of diabetic ketoacidosis (DKA), a serious life- threatening condition requiring urgent hospitalization, have been reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin tablets, or other sodium-glucose co- transporter 2 (SGLT2) inhibitors.

Fatal cases of DKA have been reported in patients taking canagliflozin tablets. 9 mmol/L (250 mg/dL) (see 8 ADVERSE REACTIONS, Description of Selected Adverse Reactions). • The risk of DKA must be considered in the event of non-specific symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, anorexia, excessive thirst and unusual fatigue or sleepiness.

If these symptoms occur, regardless of blood glucose level, APO-CANAGLIFLOZIN treatment should be immediately discontinued, and patients should be assessed for DKA immediately. • APO-CANAGLIFLOZIN should not be used for the treatment of DKA or in patients with a history of DKA.

• Nephropathy may increase the risk of DKA during treatment with APO-CANAGLIFLOZIN. • APO-CANAGLIFLOZIN is not indicated, and should not be used, in patients with type 1 diabetes. • See 7 WARNINGS AND PRECAUTIONS, Endocrine and Metabolism.

Lower Limb Amputation • An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin tablets use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.

, Endocrine and Metabolism. Lower Limb Amputation • An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin tablets use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.

• Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs. • Before initiating APO-CANAGLIFLOZIN, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.

• Monitor patients receiving APO-CANAGLIFLOZIN for infection, new pain or tenderness, APO-CANAGLIFLOZIN (Canagliflozin Tablets) Page 6 of 87 sores or ulcers involving the lower limbs, and discontinue APO-CANAGLIFLOZIN if these complications occur.

• See 7 WARNINGS AND PRECAUTIONS, Cardiovascular. 1 Dosing Considerations • Renal function should be assessed before initiating APO-CANAGLIFLOZIN and periodically thereafter (see 7 WARNINGS AND PRECAUTIONS, Renal). In patients with volume depletion not previously treated with canagliflozin, normalize volume status before initiating APO-CANAGLIFLOZIN (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).

, sulfonylurea), a lower dose of insulin or the insulin secretagogue may be considered to reduce the risk of hypoglycemia (see 7 WARNINGS AND PRECAUTIONS, Endocrine and Metabolism and

• Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • Patients on dialysis (see