Trade Name(s)

  • Invokana

Ther. Class.

Pharm. Class.
sodium-glucose co-transporter 2 (SGLT2) inhibitors


  • Adjunct to diet and exercise in the management of type 2 diabetes mellitus.
  • To reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes mellitus and established cardiovascular disease.


Inhibits proximal renal tubular sodium-glucose co-transporter 2 (SGLT2), which determines reabsorption of glucose from the tubular lumen. Inhibits reabsorption of glucose, lowers renal threshold for glucose, and increases excretion of glucose in urine.

Therapeutic Effect(s):

  • Improved glycemic control.
  • Reduction in risk of cardiovascular death, nonfatal MI, and nonfatal stroke.


Absorption: Well absorbed (65%) following oral administration.

Distribution: Extensive tissue distribution.

Protein Binding: 99%

Metabolism and 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


POunknownunknown24 hr


Contraindicated in:

  • Hypersensitivity;
  • Severe renal impairment (eGFR <45 mL/min/1.73 m2 ), end-stage renal disease or on dialysis;
  • Type 1 diabetes;
  • Severe hepatic impairment;
  • Lactation: Avoid use, discontinue breast feeding or discontinue canagliflozin.

Use Cautiously in:

  • eGFR <60 mL/min/1.73 m2  (monitor frequently) (↑ risk of adverse reactions related to ↓ intravascular volume);
  • History of pancreatitis, pancreatic surgery, reduced caloric intake due to illness or surgery, or alcohol abuse (↑ risk of ketoacidosis);
  • Hypovolemia, chronic kidney disease, HF, or concurrent use of diuretics, NSAIDs, ACE inhibitors, or ARBs (↑ risk of acute kidney injury);
  • Previous amputation, peripheral vascular disease, neuropathy, or diabetic foot infection (↑ risk of lower limb amputation);
  • Geri:  ↑ risk of adverse reactions related to ↓ intravascular volume;
  • Hypotension (correct prior to treatment, especially if eGFR 30–60 mL/min, age >75 yr, or concurrent use of loop diuretics, ACE inhibitors, or ARBs;
  • OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
  • Pedi:  Safety and effectiveness not established.

Adverse Reactions/Side Effects

CV: hypotension

Endo: hypoglycemia (↑ with other medications)

F and E: KETOACIDOSIS, hypermagnesemia, hyperphosphatemia, thirst

GI: abdominal pain, constipation, nausea

GU: NECROTIZING FASCIITIS OF PERINEUM (FOURNIER'S GANGRENE), UROSEPSIS, female mycotic infections, acute kidney injury, glucosuria, male mycotic infections, ↓ renal function, urinary tract infection (including pyelonephritis), ↑ urination, vulvovaginal pruritus

Metabolic: hyperlipidemia

MS: bone fractures, lower limb amputation


* CAPITALS indicate life-threatening.
Underline indicate most frequent.



  • Blood levels are ↓ by  UGT inducers  including phenobarbital, phenytoin, rifampin, and  ritonavir ; ↑ dose may be required.
  • ↑ risk of hypoglycemia with  insulin  or  insulin secretagogues ; dose adjustments may be required.
  • May ↑ blood levels and effects of  digoxin ; levels should be monitored.
  • ↑ risk of hyperkalemia with  potassium-sparing diuretics  or  medications that interfere with the renin-angiotensin-aldosterone system.
  • Concurrent use with NSAIDs, diuretics, ACE inhibitors, or  angiotensin receptor blockers  may ↑ risk of acute kidney injury.


PO (Adults):  eGFR ≥ 60 mL/min/1.73 m2 – 100 mg once daily initially, may be ↑ to 300 mg once daily;   Concurrent use of UGT inducers (phenobarbital, phenytoin, rifampin, ritonavir)– if maintenance dose is 100 mg daily, may require ↑ to 300 mg daily.

Renal Impairment 
PO (Adults):  eGFR 45–60 mL/min/1.73 m2 – 100 mg once daily.


Tablets: 100 mg, 300 mg

In Combination with: metformin (Invokamet); metformin XR (Invokamet XR). See combination drugs.


  • Observe patient for signs and symptoms of hypoglycemic reactions (abdominal pain, sweating, hunger, weakness, dizziness, headache, tremor, tachycardia, anxiety).
  • Monitor for signs and symptoms of volume depletion (dizziness, feeling faint, weakness, orthostatic hypotension) after initiating therapy.
  • Monitor for infection, new pain, tenderness, erythema, swelling, sores, or ulcers involving lower limbs, with fever or malaise; discontinue canagliflozin if these occur.

Lab Test Considerations: Monitor hemoglobin A1C prior to and periodically during therapy.

  • May cause ↑ uric acid levels.
  • Monitor renal function prior to and periodically during therapy, especially in patients with eGFR <60 mL/min/1.73 m2 . May ↑ serum creatinine and ↓ eGFR.
  • May cause ↑ serum potassium, magnesium, and phosphate levels. Monitor electrolytes periodically during therapy.
  • May cause ↑ LDL-C. Monitor serum lipid levels periodically during therapy.
  • Causes positive test for urine glucose.
  • Monitor for ketoacidosis, especially during prolonged fasting for illness or surgery. May require temporary discontinuation of therapy.

Potential Diagnoses


  • Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
  • Correct volume depletion prior to beginning therapy with canagliflozin.
  • PO Administer before the first meal of the day.

Patient/Family Teaching

  • Instruct patient to take canagliflozin as directed. Take missed doses as soon as remembered, unless it is almost time for next dose; do not double doses. Advise patient to read the  Medication Guide before starting and with each Rx refill in case of changes.
  • Explain to patient that canagliflozin helps control hyperglycemia but does not cure diabetes. Therapy is usually long term.
  • Instruct patient not to share this medication with others, even if they have the same symptoms; it may harm them.
  • Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hyperglycemic or hypoglycemic episodes.
  • Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water, and notify health care professional.
  • Instruct patient in proper testing of blood glucose and urine ketones, especially during periods of stress or illness. Inform patient that canagliflozin will cause a positive test result when testing for urine glucose. Notify health care professional if significant changes occur.
  • Advise patient to notify health care professional if new pain or tenderness, sores or ulcers, or infections involving the leg or foot occur and to immediately seek care if pain or tenderness, redness, or swelling of the genitals or area from the genitals back to the rectum, along with a fever above 100.4°F or malaise occur.
  • Inform patient that canagliflozin may cause yeast infections. Women may have signs and symptoms of a vaginal yeast infection (vaginal odor, white or yellow vaginal discharge [may be lumpy or look like cottage cheese], vaginal itching). Men may have signs and symptoms of a yeast infection of the penis (redness, itching, or swelling of penis; rash on penis; foul smelling discharge from penis; pain in skin around penis). Advise patient to notify health care professional if yeast infection occurs.
  • Advise patient to notify health care professional promptly if rash; hives; or swelling of face, lips, or throat occur.
  • Inform patient of increased risk for urinary tract infections, hypotension, and bone fractures and discuss factors that may increase risk.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially other oral hypoglycemic medications.
  • Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding during therapy.

Evaluation/Desired Outcomes

  • Improved hemoglobin A1C and glycemic control in adults with Type II diabetes.
  • Reduction in risk of cardiovascular death, nonfatal MI, and nonfatal stroke.
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