Indications for INVOKAMET:
Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both canagliflozin and metformin is appropriate.
Limitations of Use:
Not for treating type 1 diabetes or diabetic ketoacidosis.
See full labeling. Individualize. Take twice daily with meals; increase dose gradually as tolerated. Currently not treated with canagliflozin or metformin: initially 50mg/500mg. Max daily dose: 300mg/2000mg. Moderate renal impairment (eGFR 45–<60mL/min/1.73m2): max canagliflozin 50mg twice daily. Concomitant UGT inducers in patients with eGFR ≥60mL/min/1.73m2: consider increase to canagliflozin 150mg twice daily; if eGFR 45–<60mL/min/1.73m2: consider other antihyperglycemics.
<18yrs: not established.
Moderate to severe renal impairment (eGFR <45mL/min/1.73m2), ESRD, 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 occurs. Discontinue at time of, or prior to intravascular iodinated contrast imaging in patients with eGFR 45–60mL/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). Assess renal function prior to starting and periodically thereafter; more frequently in elderly or if eGFR <60mL/min/1.73m2. 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. 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), increases in LDL-C; treat if needed. 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. Consider 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, increases in LDL-C, bone fractures, urosepsis, pyelonephritis.
Tabs, XR tabs—60