Overview
11 DESCRIPTION INVOKANA ® (canagliflozin) contains canagliflozin, an inhibitor of SGLT2, the transporter responsible for reabsorbing the majority of glucose filtered by the kidney. Canagliflozin, the active ingredient of INVOKANA, is chemically known as (1 S )-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol hemihydrate and its molecular formula and weight are C...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action SGLT2, expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Canagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RT G ), and thereby increases urinary glucose excretion (UGE). Canagliflozin increases the delivery of sodium to the distal tubule by blocking SGLT2-dependent glucose and sodium reabsorption. This is believed to increase tubuloglomerular feedback and reduce intraglomerular pressure. 12.
Indications
- 1 INDICATIONS AND USAGE INVOKANA (canagliflozin) is indicated: as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD). to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic...
Common Doses
- 100 mg
- 300 mg
- 60 mL
- 200 mg
Dosage
2 DOSAGE AND ADMINISTRATION Assess renal function before initiating and as clinically indicated ( 2.1 ) The recommended starting dose is 100 mg once daily, taken before the first meal of the day ( 2.2 ) Dose can be increased to 300 mg once daily in patients tolerating 100 mg once daily who have an eGFR of 60 mL/min/1.73 m 2 or greater and require additional glycemic control ( 2.2 ) Dose adjustment for patients with renal impairment may be required ( 2.3 ) See full prescribing information for INVOKANA dosage modifications due to drug interactions ( 2.
Contraindications
- 4 CONTRAINDICATIONS INVOKANA is contraindicated in patients with a serious hypersensitivity reaction to INVOKANA, such as anaphylaxis or angioedema [see Warnings and Precautions (5.8) and Adverse Reactions (6.1 , 6.2) ] . Serious hypersensitivity reaction to INVOKANA ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes and Other Ketoacidosis [see Warnings and Precautions (5.1) ] Lower Limb Amputation [see Warnings and Precautions (5.2) ] Volume Depletion [see Warnings and Precautions (5.3) ] Urosepsis and Pyelonephritis [see Warnings and Precautions (5.4) ] Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Table 7: Clinically Significant Drug Interactions with INVOKANA UGT Enzyme Inducers Clinical Impact: UGT enzyme inducers decrease canagliflozin exposure which may reduce the effectiveness of INVOKANA. Intervention: For patients with eGFR 60 mL/min/1.73 m 2 or greater, if an inducer of UGTs is administered with INVOKANA, increase the dosage to 200 mg daily in patients currently tolerating INVOKANA 100 mg daily. The total daily dosage may be increased to 300 mg daily in patients currently tolerating INVOKANA 200 mg daily who require additional glycemic control.