Canagliflozindosage

Assess renal function before initiating and as clinically indicated. Assess volume status and correct volume depletion before initiating. Individualize starting dose based on the patient's current regimen and renal function. See Table 1 in the full prescribing information for recommended starting dosages based on the current regimen. The maximum recommended total daily dosage is 300 mg of canagliflozin and 2,000 mg of metformin HCl. Initiation of INVOKAMET or INVOKAMET XR is not recommended in patients with an eGFR less than 45 mL/min/1.73 m 2, due to the metformin HCl component.

INVOKAMET: take one tablet orally twice daily with meals.

INVOKAMET XR: take two tablets orally once daily with the morning meal. Swallow whole. Never crush, cut, or chew. Gradually escalate the dosage of metformin HCl in INVOKAMET or INVOKAMET XR to reduce the risk of gastrointestinal adverse reactions with metformin HCl. Dose adjustment for patients with renal impairment may be required. See full prescribing information for INVOKAMET and INVOKAMET XR dosage modifications due to drug interactions. May need to be discontinued at time of, or prior to, iodinated contrast imaging procedures. Withhold INVOKAMET or INVOKAMET XR at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting.

2.1 Prior to

Initiation of INVOKAMET or INVOKAMET XR Assess renal function before initiating INVOKAMET or INVOKAMET XR and as clinically indicated. In patients with volume depletion, correct this condition before initiating INVOKAMET or INVOKAMET XR.

2.2 Recommended

Dosage and Administration INVOKAMET and INVOKAMET XR INVOKAMET and INVOKAMET XR contain canagliflozin and metformin HCl. For the available strengths of the canagliflozin and metformin HCl components in INVOKAMET and INVOKAMET XR,. Individualize the starting dosage of INVOKAMET or INVOKAMET XR based on the patient's current regimen as presented in Table 1 and based on renal function as presented in Table 2. INVOKAMET Take one tablet of INVOKAMET orally twice daily with meals. INVOKAMET XR Take two tablets of INVOKAMET XR orally once daily with the morning meal. Swallow each tablet whole and never crush, cut, or chew. Table 1 presents the recommended starting dosage of INVOKAMET and INVOKAMET XR based on the patient's current regimen.

Table 1: Recommended Starting Dosage Based on the Current Regimen Current Regimen INVOKAMET Recommended Dosage INVOKAMET XR Recommended Dosage Not treated with either canagliflozin or metformin HCl Total daily dosage is canagliflozin 100 mg and metformin HCl 1,000 mg Metformin HCl For patients taking an evening dosage of metformin HCl extended-release tablets, skip the last dose before starting INVOKAMET or INVOKAMET XR the following morning. Total daily dosage is canagliflozin 100 mg and the nearest appropriate total daily dosage of metformin HCl Canagliflozin The same total daily dosage of canagliflozin and a total daily dosage of metformin HCl 1,000 mg Canagliflozin and metformin HCl The same total daily dosage of canagliflozin and the nearest appropriate total daily dosage of metformin HCl Recommended Dosage for Additional Glycemic Control in Adults and Pediatric Patients Aged 10 Years and Older INVOKAMET The dosage of canagliflozin in INVOKAMET may be increased to the maximum total daily dosage of 300 mg (150 mg orally twice daily) in patients tolerating a dosage of 100 mg (50 mg twice daily) of canagliflozin. The dosage of metformin HCl in INVOKAMET may be increased to the maximum total daily dosage of 2,000 mg (1,000 mg orally twice daily), with gradual escalation to reduce the risk of gastrointestinal adverse reactions with metformin HCl. INVOKAMET XR The dosage of canagliflozin in INVOKAMET XR may be increased to the maximum total daily dosage of 300 mg orally once daily in patients tolerating a 100 mg once daily dosage of canagliflozin. The dosage of metformin HCl in INVOKAMET XR may be increased to the maximum total daily dosage of 2,000 mg once daily, with gradual escalation to reduce the risk of gastrointestinal adverse reactions with metformin HCl.

2.3 Recommended

Dosage in Adults and Pediatric Patients Aged 10 Years and Older with Renal Impairment Initiation of INVOKAMET or INVOKAMET XR is not recommended in adults or pediatric patients aged 10 years and older with an eGFR less than 45 mL/min/1.73 m 2, due to the metformin component. Table 2 provides dosage recommendations for adults and pediatric patients aged 10 years and older with renal impairment, based on eGFR.

Table 2: Recommended Dosage in Adults and Pediatric Patients Aged 10 Years and Older with Renal Impairment Estimated Glomerular Filtration Rate [eGFR (mL/min/1.73 m 2 )] Recommended Dosage of INVOKAMET or INVOKAMET XR For the dosing frequency of INVOKAMET and INVOKAMET XR, see Dosage and Administration. eGFR 45 to less than 60 The maximum total daily dosage of canagliflozin is 100 mg. eGFR 30 to less than 45 Assess the benefit risk of continuing INVOKAMET or INVOKAMET XR. The maximum total daily dosage of canagliflozin is 100 mg. eGFR less than 30 Contraindicated. If eGFR falls below 30 during treatment; discontinue INVOKAMET or INVOKAMET XR.

2.4 Concomitant

Use with UDP-Glucuronosyltransferase (UGT) Enzyme Inducers When co-administering INVOKAMET or INVOKAMET XR with an inducer of UGT (e.g., rifampin, phenytoin, phenobarbital, ritonavir), increase the total daily dosage of canagliflozin based on renal function: In patients with eGFR 60 mL/min/1.73 m 2 or greater, increase the total daily dosage of canagliflozin to 200 mg in patients currently tolerating a total daily dosage of canagliflozin 100 mg. The maximum total daily dosage of canagliflozin is 300 mg. In patients with eGFR less than 60 mL/min/1.73 m 2, increase the total daily dosage of canagliflozin to a maximum of 200 mg in patients currently tolerating a total daily dosage of canagliflozin 100 mg.

2.5 Discontinuation for

Iodinated Contrast Imaging Procedures Discontinue INVOKAMET or INVOKAMET XR at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR of less than 60 mL/min/1.73 m 2; 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 or INVOKAMET XR if renal function is stable.

2.6 Temporary

Interruption for Surgery Withhold INVOKAMET or INVOKAMET XR at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume INVOKAMET or INVOKAMET XR when the patient is clinically stable and has resumed oral intake.

2.7 Recommendations

Regarding Missed Dose If a dose is missed, instruct patients to take the dose as soon as possible. Advise patients not to double up the next dose.