Drug Detail:Invokamet (Canagliflozin and metformin [ kan-a-gli-floe-zin-and-met-for-min ])
Generic Name: CANAGLIFLOZIN 50mg, METFORMIN HYDROCHLORIDE 500mg
Dosage Form: tablet, film coated
Drug Class: Antidiabetic combinations
Prior to Initiation of INVOKAMET/INVOKAMET XR
- Assess renal function before initiating INVOKAMET/INVOKAMET XR and as clinically indicated [see Warnings and Precautions (5.1, 5.4)], Contraindications (4)].
- In patients with volume depletion, correct this condition before initiating INVOKAMET/INVOKAMET XR [see Warnings and Precautions (5.4), Use in Specific Populations (8.5, 8.6)].
Dosage Overview
- INVOKAMET dosing is one tablet, twice daily with meals.
- INVOKAMET XR dosing is two tablets, once daily with the morning meal. Swallow each tablet whole and never crush, cut, or chew.
- The starting and maintenance dose of INVOKAMET/INVOKAMET XR is based on the patient's current regimen and renal function [see Dosage and Administration (2.3, 2.4)].
- The maximum recommended daily dose is canagliflozin 300 mg and metformin HCl 2,000 mg in patients with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 or greater. The recommended dosage for patients with renal impairment is shown in Table 1 [see Dosage and Administration (2.4)].
Starting Dose Based on Patient's Current Regimen
Individualize the starting dose of INVOKAMET/INVOKAMET XR based on the patient's current regimen and renal function [see Dosage and Administration (2.4)]:
Patients Currently not Treated with Either Canagliflozin or Metformin HCl
- INVOKAMET: One tablet, twice daily, each tablet containing canagliflozin 50 mg and metformin HCl 500 mg;
- INVOKAMET XR: Two tablets, once daily, each tablet containing canagliflozin 50 mg and metformin HCl 500 mg.
Patients on Metformin HCl
- INVOKAMET: One tablet, twice daily, where the total daily dose contains canagliflozin 100 mg and the same, or nearest appropriate, daily dose of metformin HCl;
- INVOKAMET XR: Two tablets, once daily, where the total daily dose contains canagliflozin 100 mg and the patient's same, or nearest appropriate, daily dose of metformin HCl.
Patients on Canagliflozin
- INVOKAMET: One tablet, twice daily, where the total daily dose contains the same daily dose of canagliflozin and metformin HCl 1,000 mg;
- INVOKAMET XR: Two tablets, once daily, where the total daily dose contains the patient's same daily dose of canagliflozin and metformin HCl 1,000 mg.
Patients Already Treated with Canagliflozin and Metformin HCl
- INVOKAMET: One tablet, twice daily, where the total daily dose contains the same daily dose of canagliflozin and the same, or nearest appropriate, daily dose of metformin HCl;
- INVOKAMET XR: Two tablets, once daily, where the total daily dose contains the same daily dose of canagliflozin and the same, or nearest appropriate, daily dose of metformin HCl.
Patients with eGFR of 60 mL/min/1.73 m2 or Greater and Require Additional Glycemic Control
- INVOKAMET: For patients tolerating canagliflozin 50 mg twice daily, increase the dose of canagliflozin to 150 mg twice daily, with gradual metformin HCl dose escalation based on tolerability [see Adverse Reactions (6.1)];
- INVOKAMET XR: For patients tolerating a daily dose of canagliflozin 100 mg, increase the dose to 300 mg once daily, with gradual metformin HCl dose escalation based on tolerability [see Adverse Reactions (6.1)].
Recommended Dosage for Patients with Renal Impairment
- Initiation of INVOKAMET or INVOKAMET XR is not recommended in patients with an eGFR less than 45 mL/min/1.73 m2, due to the metformin component.
- Table 1 has dosage recommendations based on eGFR [see Use in Specific Populations (8.6), Clinical Studies (14.3)].
| estimated Glomerular Filtration Rate eGFR (mL/min/1.73 m2) |
Recommended Dosage |
|---|---|
| eGFR 60 or greater | [See Dosage and Administration (2.3)]. |
| eGFR 45 to less than 60 | Limit the dose of canagliflozin component to 100 mg daily (two 50 mg tablets). |
| eGFR 30 to less than 45 | Assess the benefit risk of continuing INVOKAMET or INVOKAMET XR; limit the dose of canagliflozin component to 100 mg daily (two 50 mg tablets). |
| eGFR less than 30 | Contraindicated; discontinue INVOKAMET or INVOKAMET XR [see Contraindications (4)]. |
| On dialysis | Contraindicated [see Contraindications (4)]. |
Concomitant Use with UDP-Glucuronosyltransferase Enzyme Inducers
Patients with eGFR 60 mL/min/1.73 m2 or greater
If an inducer of UDP-Glucuronosyltransferase (UGT) (e.g., rifampin, phenytoin, phenobarbital, ritonavir) is co-administered with INVOKAMET/INVOKAMET XR, increase the total daily dose of canagliflozin to 200 mg in patients currently tolerating a total daily dose of canagliflozin 100 mg. The total daily dose of canagliflozin may be increased to a maximum of 300 mg in patients currently tolerating canagliflozin 200 mg and who require additional glycemic control [see Drug Interactions (7)].
Discontinuation for Iodinated Contrast Imaging Procedures
Discontinue INVOKAMET/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 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/INVOKAMET XR if renal function is stable [see Warnings and Precautions (5.1)].
