Therapeutic Classification: antidiabetics
Pharmacologic Classification: sodium-glucose co-transporter 2 (SGLT2) inhibitors
Absorption: Well absorbed (65%) following oral administration.
Distribution: Extensive tissue distribution.
Protein Binding: 99%
Metabolism/Excretion: Mostly metabolized by UDP-glucuronyl transferases (UGT) to inactive metabolites, minimal metabolism by CYP3A4 (7%). 50% excreted in feces as parent drug and metabolites; 33% as metabolites in urine; <1% excreted in urine as unchanged drug.
Half-Life: 10.6 hr
Improvement in Glycemic Control in Type 2 Diabetes
- PO (Adults and Children ≥10 yr): 100 mg once daily initially; may ↑ to 300 mg once daily if additional glycemic control needed; Concurrent use of UGT inducers (phenobarbital, phenytoin, rifampin, ritonavir): If patient tolerating canagliflozin 100 mg once daily, ↑ to 200 mg once daily; if patient tolerating canagliflozin 200 mg once daily and requires addition glycemic control, ↑ to 300 mg once daily.
Renal Impairment
- PO (Adults and Children ≥10 yr): eGFR 30–<60 mL/min/1.73 m2: 100 mg once daily. eGFR <30 mL/min/1.73 m2: Initiation of therapy not recommended; patients with albuminuria >300 mg/day who are already receiving therapy may continue with 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, cardiovascular death, and hospitalization for HF. Concurrent use of UGT inducers (phenobarbital, phenytoin, rifampin, ritonavir) and eGFR <60 mL/min/1.73 m2: If patient tolerating canagliflozin 100 mg once daily, ↑ to 200 mg once daily; if patient requires additional glycemic control, consider adding another antihyperglycemic agent.
Reduction in Risk of Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease or Reduction in Risk of End-Stage Kidney Disease, Doubling of Serum Creatinine, Cardiovascular Death, and Hospitalization for HF in Patients with Type 2 Diabetes Mellitus and Diabetic Nephropathy with Albuminuria >300 mg/day
- PO (Adults ): 100 mg once daily initially; Concurrent use of UGT inducers (phenobarbital, phenytoin, rifampin, ritonavir): If patient tolerating canagliflozin 100 mg once daily, ↑ to 200 mg once daily; if patient tolerating canagliflozin 200 mg once daily and requires addition glycemic control, ↑ to 300 mg once daily.
Renal Impairment
- PO (Adults ): eGFR 30–<60 mL/min/1.73 m2: 100 mg once daily. eGFR <30 mL/min/1.73 m2: Initiation of therapy not recommended; patients with albuminuria >300 mg/day who are already receiving therapy may continue with 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, cardiovascular death, and hospitalization for HF. Concurrent use of UGT inducers (phenobarbital, phenytoin, rifampin, ritonavir) and eGFR <60 mL/min/1.73 m2: If patient tolerating canagliflozin 100 mg once daily, ↑ to 200 mg once daily; if patient requires additional glycemic control, consider adding another antihyperglycemic agent.
