Recommended Dosage

• Individualize the starting dose of INVOKAMET XR (canagliflozin and metformin hydrochloride extended-release), taken once-daily with the morning meal, based on the effectiveness and tolerability of the patient's current regimen:

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  In patients currently not treated with either canagliflozin or metformin, initiate therapy with two INVOKAMET XR tablets, each tablet containing canagliflozin 50 mg and metformin 500 mg [see Clinical Studies (14.1)].

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  In patients on metformin, switch to two INVOKAMET XR tablets, where two tablets equal a starting dose of canagliflozin 100 mg daily and the patient's current total daily dose (or nearest appropriate) of metformin.

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  In patients on canagliflozin, switch to two INVOKAMET XR tablets, where two tablets equal the patient's current total daily dose of canagliflozin and a starting dose of metformin 1000 mg daily.

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  In patients already treated with canagliflozin and metformin, switch to two INVOKAMET XR tablets containing the same total daily dose of canagliflozin and the same, or nearest appropriate, total daily dose of metformin.

• In patients that require additional glycemic control that are taking a total daily dose of canagliflozin 100 mg, the INVOKAMET XR dose can be increased to canagliflozin 300 mg once daily [see Dosage Forms and Strengths (3) and Clinical Studies (14.1)].
• The dose of metformin should be gradually escalated to reduce the gastrointestinal side effects due to metformin [see Dosage Forms and Strengths (3) and Clinical Studies (14.1)].
• Patients taking an evening dose of metformin XR should skip their last dose before starting INVOKAMET XR the following morning.
• In patients with volume depletion not previously treated with canagliflozin, correct this condition before initiating INVOKAMET XR [see Warnings and Precautions (5.3), Use in Specific Populations (8.5, 8.6), and Patient Counseling Information (17)].
• Adjust dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of metformin 2000 mg and canagliflozin 300 mg in patients with an eGFR of 60 mL/min/1.73 m2 or greater [see Dosage and Administration (2.2)].

Recommended Dosage for Patients with Renal Impairment

• Assess renal function before initiating INVOKAMET XR and periodically thereafter.
• INVOKAMET XR is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2 [see Contraindications (4) and Warnings and Precautions (5.1, 5.4)].
• Limit the dose of INVOKAMET XR to two tablets, each tablet containing canagliflozin 50 mg, in patients with moderate renal impairment with an eGFR of 45 to less than 60 mL/min/1.73 m2.

Concomitant Use with UDP-Glucuronosyl Transferase (UGT) Enzyme Inducers

If an inducer of UGTs (e.g., rifampin, phenytoin, phenobarbital, ritonavir) is co-administered with INVOKAMET XR, consider increasing the dose of canagliflozin to a total daily dose of 300 mg once daily in patients currently tolerating INVOKAMET XR with 100 mg canagliflozin once daily who have an eGFR of 60 mL/min/1.73 m2 or greater and require additional glycemic control [see Drug Interactions (7.2)].

Consider another antihyperglycemic agent in patients with an eGFR of 45 to less than 60 mL/min/1.73 m2 receiving concurrent therapy with a UGT inducer.

Discontinuation for Iodinated Contrast Imaging Procedures

Discontinue INVOKAMET XR at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 45 and 60 mL/min/1.73 m2; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart INVOKAMET XR if renal function is stable [see Warnings and Precautions (5.1)].

Important Administration Instructions

• Take INVOKAMET XR tablets once daily with the morning meal.
• INVOKAMET XR must be swallowed whole and never crushed, cut, or chewed [see Patient Counseling Information (17)].