Tablets: 100 mg and 300 mg.
As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus: Start with 100 mg before the first meal of the day. Dose can be increased to 300 mg once daily in patients who have an eGFR of 60 mL/min/1.73 m^2 or greater if greater glycemic control is needed and the 100 mg dose is tolerated. In patients with an eGFR between 45-60 mL/min/1.73 n^2, the maximum dose is 100 mg.
Monitor: RFT, Lipid Panel, K.
Pharmacology/Pharmacokinetics:
Canagliflozin lowers blood glucose by inhibiting the sodium-glucose co-transporter 2 which is found in the proximal renal tubules and is responsible for the majority of reabsorption of filtered glucose from the tubular lumen. By reducing reabsorption of glucose from the tubular lumen and reducing the renal threshold for glucose, canagliflozin effectively increases urinary glucose excretion. It also appears to delay gastrointestinal glucose absorption and reduce postprandial glucose. Oral bioavailability is approximately 65% with no effect from the presence of food. However because of its effects on gastrointestinal glucose absorption, it is recommended to be taken before the first meal of the day. Metabolism occurs primarily via O-glucuronidation. The apparent half-life is between 10 to 13 hours depending on the dose. Excretion occurs primarily through the urine.
Drug Interactions:
Canagliflozin does not affect the CYP enzyme system to any major degree. It does increase AUC and Cmax of digoxin by 20% and 36% at the 300 mg dose. Rifampin decreases canagliflozin AUC by 51%. Hyperkalemia may occur when used with potassium-sparing diuretics and ACE inhibitors.
Contraindication/Precautions:
Contraindicated in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m^2), end stage renal disease (ESRD), or patients on dialysis. Use with caution in patients with renal impairment of eGFR less than 60 mL/min/1.73 m^2. Use with caution in the elderly, patients taking diuretics or medications that interfere with the renin-angiotensin-aldosterone system, and in patients with low systolic blood pressure due to potential for symptomatic hypotension. May cause ketoacidosis, hyperkalemia, elevated LDL-C, increased risk of bone fractures, and hypoglycemia in patients on insulin or insulin secretagogues. Use appropriate precautions and monitor for these conditions. Avoid use during pregnancy. Pregnancy Category D.
Adverse Effects:
The most common adverse effects include urinary tract infections, genital mycotic infections, and increased urination. Less common adverse effects include increased thirst, constipation, nausea, and vulvovaginal pruritus. Infrequent but potentially severe adverse effects include systemic hypotension including dizziness and falls, increased risk of bone fractures, and hyperkalemia.
Take before the first meal of the day.
Closely follow recommended diet and exercise recommendation.
It is important to monitor your blood glucose while taking this medication.
Contact a physician if the above side effects are severe or persistent.
Promptly report episodes of dizziness to your physician.
Keep well hydrated during therapy by drinking plenty of fluids.
Avoid excessive use of alcohol.
Avoid salt substitutes containing potassium.
Store in a cool, dry place away from sunlight and children.
If a dose is missed, take it as soon as possible. If it is closer to the time of your next dose than the dose you missed, skip the missed dose and return to your dosing schedule. Do not double doses.
