INVOKAMET is a sodium-glucose co-transporter 2 (SGLT2) inhibitor and biguanide combination product indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing metformin or canagliflozin or in patients already being treated with both canagliflozin and metformin (1)

Limitation of use:

Not for treatment of type 1 diabetes or diabetic ketoacidosis (1)

• Individualize based on the patient's current regimen (2)
• Take twice daily with meals, with gradual dose escalation to reduce the gastrointestinal side effects due to metformin (2.1)
• Do not exceed a daily dose of metformin 2,000 mg and canagliflozin 300 mg; INVOKAMET is limited to canagliflozin 50 mg twice daily in patients with an eGFR of 45 to less than 60 mL/min/1.73 m2 (2.1, 2.2)
• Assess renal function before initiating INVOKAMET. Do not initiate or continue INVOKAMET if creatinine levels are greater than or equal to 1.5 mg/dL for males or 1.4 mg/dL for females, or if eGFR is persistently below 45 mL/min/1.73 m2 (2.2, 4)

Film-coated tablets:

• Canagliflozin 50 mg and metformin hydrochloride 500 mg
• Canagliflozin 50 mg and metformin hydrochloride 1,000 mg
• Canagliflozin 150 mg and metformin hydrochloride 500 mg
• Canagliflozin 150 mg and metformin hydrochloride 1,000 mg (3)
CONTRAINDICATIONS

• Renal impairment, ESRD, or on dialysis (4, 5.1, 5.3)
• Metabolic acidosis, including diabetic ketoacidosis (1, 4, 5.1)
• History of serious hypersensitivity reaction to canagliflozin or metformin (4, 5.8
WARNINGS AND PRECAUTIONS

• Lactic acidosis: Warn against excessive alcohol use. INVOKAMET is not recommended in hepatic impairment or hypoxic states. Ensure normal renal function before initiating and at least annually thereafter (5.1, 5.3, 5.5, 5.10, 5.11)
• Hypotension: Before initiating INVOKAMET, assess volume status and correct hypovolemia in patients with renal impairment, the elderly, in patients with low systolic blood pressure, or on diuretics, ACEi, or ARB. Monitor for signs and symptoms during therapy (5.2)
• Impairment in Renal Function: Monitor renal function during therapy (5.3)
• Radiological Studies and Surgical Procedures: Temporarily discontinue for radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids (5.3)
• Hyperkalemia: Monitor potassium levels in patients with impaired renal function and in patients predisposed to hyperkalemia (5.4)
• Hypoglycemia: Consider a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia when used in combination with INVOKAMET (5.6)
• Genital mycotic infections: Monitor and treat if indicated (5.7)
• Hypersensitivity reactions: Discontinue INVOKAMET and monitor until signs and symptoms resolve (5.8)
• Vitamin B12 deficiency: Metformin may lower vitamin B12 levels. Monitor hematologic parameters annually (5.9)
• Increased LDL-C: Monitor LDL-C and treat per standard of care (5.12)

• Most common adverse reactions associated with canagliflozin (5% or greater incidence): female genital mycotic infections, urinary tract infection, and increased urination (6.1)
• Most common adverse reactions associated with metformin (5% or greater incidence) are diarrhea, nausea, vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Cationic drugs: May reduce metformin elimination (7.1)
• UGT inducers (e.g., rifampin): Canagliflozin exposure is reduced. Consider increasing canagliflozin dose from 50 mg to 150 mg twice daily (2.3, 7.2)
• Digoxin: Monitor digoxin levels (7.2)

• Pregnancy: Use during pregnancy only if the potential benefit justifies the potential risk to the fetus (8.1)
• Nursing mothers: Discontinue drug or nursing (8.3)
• Geriatrics: Higher incidence of adverse reactions related to reduced intravascular volume (5.2, 6.1, 8.5)