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, doubling of serum creatinine, CV death, and hospitalization for heart failure in adults with T2DM and diabetic nephropathy with albuminuria >300mg/day.
Limitations of Use:
Not for treating type 1 diabetes or diabetic ketoacidosis.
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. Renal impairment (eGFR 45–<60mL/min/1.73m2 or eGFR 30–<45mL/min/1.73m2 with albuminuria >300mg/day): limit 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.
<18yrs: not established.
Canagliflozin: severe renal impairment (eGFR <30mL/min/1.732) in patients being treated for glycemic control. Dialysis. Metformin: severe renal impairment (eGFR <30mL/min/1.73m2) or on dialysis. Metabolic acidosis, diabetic ketoacidosis.
Lactic acidosis. Lower limb amputation.
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. Correct volume depletion before initiating. Monitor for symptomatic hypotension in renal impairment (eGFR <60mL/min/1.73m2), elderly, low systolic BP, concomitant diuretics or drugs that interfere with the RAA system (eg, ACEIs, ARBs). 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). Evaluate renal function prior to starting and periodically thereafter; more frequently in elderly. Risk of acute kidney injury in hypovolemia, chronic renal insufficiency, CHF, and concomitant drugs (eg, diuretics, ACEIs, ARBs, NSAIDs). Consider temporarily discontinuing in reduced oral intake or fluid losses; monitor for acute kidney injury; discontinue and treat if occurs. Monitor serum K+ levels in patients predisposed to hyperkalemia. Consider risk factors for bone fractures before initiation. Necrotizing fasciitis of the perineum (Fournier's gangrene); discontinue and treat immediately if suspected; use alternative antidiabetic. Elderly, debilitated, uncompensated strenuous exercise, malnourished or deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. Discontinue if hypersensitivity reactions occur. Monitor for genital mycotic infections, UTIs, hematology (esp. serum Vit. B12); treat if needed. Hepatic impairment: avoid. Pregnancy (during 2nd & 3rd trimesters), nursing mothers: not recommended.
Sodium-glucose co-transporter 2 (SGLT2) inhibitor + biguanide.
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 Adults. Concomitant digoxin: monitor. May need a lower dose of concomitant insulin/insulin secretagogue to reduce risk of hypoglycemia. May cause false (+) urine glucose tests or unreliable measurements of 1, 5-AG assay; use alternative methods to monitor glycemic control.
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, urosepsis, pyelonephritis.
Tabs, XR tabs—60