NVOKAMET- canagliflozin and metformin hydrochloride tablet, film coated
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., cationic drugs 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 and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1)].
1 INDICATIONS AND USAGE
? INVOKAMET (canagliflozin and metformin hydrochloride) 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 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 (canagliflozin and metformin hydrochloride) based on the patient�s current regimen:
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In patients currently not treated with either canagliflozin or metformin, initiate therapy with INVOKAMET containing canagliflozin 50 mg and metformin 500 mg [see Clinical Studies (14.1)] ;
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In patients on metformin, switch to INVOKAMET containing canagliflozin 50 mg and the same, or nearest appropriate, daily dose of metformin;
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In patients on canagliflozin, switch to INVOKAMET containing metformin 500 mg with the same daily dose of canagliflozin;
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In patients already treated with canagliflozin and metformin, switch to INVOKAMET containing the same daily dose of canagliflozin and the same, or nearest appropriate, daily dose of metformin.
? Take one INVOKAMET tablet twice daily with meals; in patients tolerating canagliflozin 50 mg twice daily who have an eGFR of 60 mL/min/1.73 m2 or greater and require additional glycemic control, INVOKAMET dose can be increased for the canagliflozin component to 150 mg twice daily, with gradual metformin dose escalation to reduce the gastrointestinal side effects due to metformin [see Dosage Forms and Strengths (3) and Clinical Studies (14.1)].
In patients with volume depletion not previously treated with canagliflozin, correct this condition before initiating INVOKAMET [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)].
