Canagliflozin (6 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, TABLET, EXTENDED RELEASE.
Routes of administration: ORAL.
Brand Names
- CANAGLIFLOZIN
- CANAGLIFLOZIN AND METFORMIN HYDROCHLORIDE
- CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE
- INVOKAMET
- INVOKAMET XR
- INVOKANA
Indications and Usage
INVOKANA (canagliflozin) is indicated: as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older 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 nephropathy with albuminuria greater than 300 mg/day.
Contraindications
INVOKANA is contraindicated in patients with a serious hypersensitivity reaction to INVOKANA, such as anaphylaxis or angioedema [see Warnings and Precautions (5.6)and Adverse Reactions (6.1, 6.2)] .
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)] Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections [see Warnings and Precautions (5.4)] Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions (5.5)] Hypersensitivity Reactions [see Warnings and Precautions (5.6)] Bone Fracture [see Warnings and Precautions (5.7)]
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 2or 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. For patients with eGFR less than 60 mL/min/1.73 m 2, if an inducer of UGTs is administered with INVOKANA, increase the dosage to 200 mg daily in patients currently tolerating INVOKANA 100 mg daily. Consider adding another antihyperglycemic agent in patients who require additional glycemic control [see Dosage and Administration (2.3)and Clinical Pharmacology (12.3)] . Examples: Rifampin, phenytoin, phenobarbital, ritonavir Insulin or Insulin Secretagogues Clinical Impact: The risk of hypoglycemia is increased when INVOKANA is used concomitantly with insulin secretagogues (e.g., sulfonylurea) or insulin. Intervention: Concomitant use may require a lower dosage of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. Digoxin Clinical Impact: Canagliflozin increases digoxin exposure [see Clinical Pharmacology (12.3)] . Intervention: Monitor patients taking INVOKANA with concomitant digoxin for a need to adjust the dosage of digoxin. Lithium Clinical Impact: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during INVOKANA initiation and dosage changes. Drug/Laboratory Test Interference Positive Urine Glucose Test Clinical Impact: SGLT2 inhibitors increase urinary glucose excretion which will lead to positive urine glucose tests. Intervention: Monitoring glycemic control with urine glucose t
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.
Overdosage
In the event of an overdose, contact the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. It is also reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive treatment as dictated by the patient’s clinical status. Canagliflozin was negligibly removed during a 4-hour hemodialysis session. Canagliflozin is not expected to be dialyzable by peritoneal dialysis.