INVOKAMET XR- canagliflozin and metformin hydrochloride tablet, film coated, extended release
Janssen Pharmaceuticals, Inc.
WARNING: LACTIC ACIDOSIS
Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1)].
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information [see Dosage and Administration (2.2), Contraindications (4), Warnings and Precautions (5.1), Drug Interactions (7), and Use in Specific Populations (8.6, 8.7)].
If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET� XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1)].
1 INDICATIONS AND USAGE
INVOKAMET XR (canagliflozin and metformin hydrochloride extended release) is indicated as an 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
INVOKAMET XR is not recommended in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
2 DOSAGE AND ADMINISTRATION
2.1 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 (5.2), 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)].