Indications for: INVOKAMET

Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). To reduce the risk of major cardiovascular (CV) events (eg, CV death, nonfatal MI and stroke) in adults with T2DM and established CV disease. To reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, CV death, and hospitalization for heart failure (HF) in adults with T2DM and diabetic nephropathy with albuminuria >300mg/day.

Limitations of Use:

Not recommended in patients with type 1 diabetes; may increase risk of diabetic ketoacidosis.

Adult Dosage:

Base dose on current regimen and renal function. Individualize. Take with meals. Currently not treated with canagliflozin or metformin: initially 50mg/500mg twice daily. Patients on individual components or already on combination: see full labeling. eGFR ≥60mL/min/1.73m2: max 300mg/2000mg daily. eGFR ≥60mL/min/1.73m2 and require additional glycemic control: if tolerating canagliflozin 50mg twice daily; may increase to 150mg twice daily, with gradual metformin dose escalation based on tolerability. Due to the metformin component, initiation is not recommended in patients with renal impairment (eGFR <45mL/min/1.73m2). Renal impairment (eGFR 45–<60mL/min/1.73m2): limit the canagliflozin component to 100mg daily; (eGFR 30–<45mL/min/1.73m2): assess the benefit/risk of continuing therapy; limit the canagliflozin component to 100mg daily. Concomitant UGT inducers (eGFR ≥60mL/min/1.73m2): increase to canagliflozin 200mg daily in patients currently tolerating 100mg, may increase to max 300mg daily in those tolerating 200mg and require additional glycemic control; (eGFR <60mL/min/1.73m2): increase to max 200mg daily in patients currently tolerating 100mg.

Children Dosage:

<18yrs: not established.

INVOKAMET Contraindications:

Severe renal impairment (eGFR <30mL/min/1.73m2) or on dialysis. Metabolic acidosis, diabetic ketoacidosis.

Boxed Warning:

Lactic acidosis.

INVOKAMET Warnings/Precautions:

Increased risk of metformin-associated lactic acidosis in renal or hepatic impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors), ≥65yrs of age, undergoing radiological contrast study, surgery and other procedures, hypoxic states, and excessive alcohol intake; discontinue if lactic acidosis is suspected. Discontinue at time of, or prior to intravascular iodinated contrast imaging in patients with eGFR <60mL/min/1.73m2, history of hepatic impairment, alcoholism, heart failure, or will be given intra-arterial contrast; reevaluate eGFR 48hrs after procedure and restart therapy if renally stable. Increased risk of lower limb amputations; monitor for infection, new pain or tenderness, sores or ulcers in lower limbs, and discontinue if occur. Consider risk factors for amputation (eg, prior amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers) before initiation. Assess renal function (esp. eGFR) prior to starting, then annually, or as clinically indicated; more frequently in elderly. Prior to initiation, assess and correct volume status in those with renal impairment, elderly, or taking loop diuretics; monitor during therapy. Assess for ketoacidosis in presence of signs/symptoms of metabolic acidosis, regardless of blood glucose levels; discontinue if suspected, evaluate and treat; consider risk factors before initiation (eg, pancreatic insulin deficiency, caloric restriction, alcohol abuse). Consider temporarily discontinuing prior to scheduled surgery (for ≥3 days) or other clinical situations (eg, prolonged fasting due to illness or post-surgery). Necrotizing fasciitis of the perineum (Fournier's gangrene); discontinue and treat immediately if suspected; use alternative antidiabetic. Discontinue if hypersensitivity reactions occur. Consider risk factors for bone fractures before initiation. Monitor for genital mycotic infections, UTIs (including urosepsis, pyelonephritis), hematology (esp. serum Vit. B12); treat if needed. Hepatic impairment: not recommended. Pregnancy (during 2nd & 3rd trimesters), nursing mothers: not recommended.

See Also:

INVOKAMET Classification:

Sodium-glucose co-transporter 2 (SGLT2) inhibitor + biguanide.

INVOKAMET Interactions:

Concomitant cationic drugs that interfere with renal tubular transport systems (eg, ranolazine, vandetanib, dolutegravir, cimetidine) may increase metformin levels. Increased risk of lactic acidosis with topiramate, other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, dichlorphenamide); monitor. Diuretics, steroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, sympathomimetics, nicotinic acid, CCBs, and isoniazid may cause hyperglycemia. Avoid excessive alcohol. Antagonized by UGT inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir): see Adult dose. Concomitant digoxin: monitor. May need a lower dose of concomitant insulin or insulin secretagogue (eg, sulfonylurea) to reduce risk of hypoglycemia. Canagliflozin may antagonize serum lithium concentrations; monitor levels more frequently. Canagliflozin will lead to false (+) urine glucose tests or unreliable measurements of 1, 5-AG assay; use alternative methods to monitor glycemic control.

Adverse Reactions:

Female genital mycotic infections, UTI (may be serious), increased urination, GI upset, flatulence, asthenia, indigestion, abdominal discomfort, headache; lactic acidosis (rare), lower limb amputation, hypotension, ketoacidosis (may be fatal), acute kidney injury, hyperkalemia, hypoglycemia, bone fractures.

Generic Drug Availability:


How Supplied:

Tabs, XR tabs—60