Canagliflozin

Class and Category

Pharmacologic Class: Sodium-glucose co-transporter 2 (SGLT2) inhibitor
Therapeutic ClassAnti-diabetic

Indications and Dosages

To control blood glucose levels in type 2 diabetes mellitus; to reduce the risk of major adverse cardiovascular events such as nonfatal myocardial infarction and nonfatal stroke in patients with type 2 diabetes mellitus and established cardiovascular disease; to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in patients with type 2 diabetes melitus and diabetic nephropathy with albuminuria greater than 300 mg/day.
CAPSULES, TABLETS (CALCIUM ACETATE)
Adults: 
100 mg once daily before first meal of the day, followed by dosage increase to 300 mg once daily before first meal of the day, if needed, and patient has a glomerular filtration rate of 60 ml/min or greater. 
Maximum: 300 mg once daily before first meal of the day.
Dosage Adjustment:
For patients with glomerular filtration rate less than 60 ml/min but at least 45 ml/min dosage limited to 100 mg once daily. For patients receiving an UDP-glucuronosyltransferase (UGT) enzyme inducer such as phenobarbital, phenytoin, rifampin, or ritonavir and have a glomerular filtration rate of 60 ml/min or greater, dosage may be increased to 200 mg once daily if patient is tolerating 100 mg daily or increased to 300 mg once daily if patient is tolerating 200 mg daily. For patients receiving an UGT enzyme inducer as indicated above and the glomerular filtration rate is less than 60 ml/min, dosage increased to 200 mg once daily in patients tolerating 100 mg once daily.


Mechanism of Action
Inhibits sodium-glucose co-transporter 2 (SGLT2) responsible for the majority of the reabsorption of filtered glucose from the tubular lumen in the kidneys. By inhibiting SGLT2, reabsorption of filtered glucose is reduced along with a lowering of the renal threshold for glucose, which increases urinary glucose excretion.

Contraindications
Hypersensitivity to canagliflozin or its components, severe renal impairment (glomerular filtration rate less than 30 ml/min), use of dialysis.

Interactions
DRUGS
Digoxin: Possibly increased serum digoxin levels and digitalis toxicity
Insulin, insulin secretagogues: Possibly increased risk of hypoglycemia
Phenobarbital, phenytoin, rifampin, ritonavir: Decreased effectiveness of canagliflozin

Adverse Reactions
CNS: Asthenia, excessive thirst, fatigue, postural dizziness, syncope
CV: Elevation of low-density lipoprotein cholesterol (LDL-C) and non-highdensity lipoprotein cholesterol (non-HDL-C), hypotension, orthostatic hypotension
ENDO: Hypoglycemia, ketoacidosis
EENT: Dry mouth
GI: Abdominal pain, constipation, nausea, pancreatitis
GU: Acute renal failure, decreased glomerular filtration rate, elevated serum creatinine levels, genital mycotic infections, necrotizing fasciitis of the perineum (Fournier’s gangrene), pyelonephritis, polyuria, renal impairment, UTIs, vulvovaginal pruritus, urosepsis
HEME: Elevated hemoglobin
MS: Bone fracture, decreased bone density, lower limb amputation
SKIN: Erythema, photosensitivity, pruritus, rash, urticaria
Other: Anaphylaxis, angioedema, dehydration, elevated phosphate levels, hyperkalemia, hypermagnesemia

Childbearing Considerations
PREGNANCY
  • Drug may cause fetal harm by adversely affecting kidney function of the fetus.
  • Drug is not recommended during the second and third trimester of pregnancy.

LACTATION
  • It is not known if drug is present in breast milk.
  • Drug should not be given to women who are breastfeeding since kidney maturation in infant continues for 2 years following birth.


Nursing Considerations
  • Use drug cautiously in patients with chronic kidney insufficiency, congestive heart failure, and decreased blood volume, and in patients taking medications such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, diuretics, and NSAIDs because these conditions and treatments may predispose the patient to acute kidney injury while receiving canagliflozin. Ensure that kidney function has been assessed prior to start of canagliflozin therapy and then periodically thereafter.
  • Know that patients with volume depletion should have the condition corrected before canagliflozin therapy is begun because drug causes intravascular volume contraction. Patients, especially at risk for symptomatic hypotension caused by volume depletion, include patients with impaired renal function, the elderly, patients taking either diuretics or drugs that interfere with the renin–angiotensin– aldosterone system, or patients with low systolic blood pressure.
  • Expect drug to be temporarily discontinued in patients who develop a reduced oral intake, such as in an acute illness or fasting, or who experience excessive fluid losses because of significant heat exposure or gastrointestinal illness, to reduce risk of acute kidney injury.
  • Be aware that canagliflozin dosage should only be increased in patients who have at least a glomerular filtration rate of 60 ml/min and need greater glucose control.
  • Assess renal function, as ordered prior to starting canagliflozin therapy and then periodically thereafter, because canagliflozin may cause renal impairment, especially in patients with hypovolemia. Expect drug to be discontinued if patient develops acute kidney injury. Also monitor patient for a UTI, because canagliflozin increases risk of UTIs. Report promptly and expect to treat because the UTI can quickly become serious, developing into pyelonephritis and urosepsis.
  • Monitor serum potassium levels regularly, as ordered, during canagliflozin therapy in patients with impaired renal function and in patients predisposed to hyperkalemia due to medications or other medical conditions.
  • Monitor patient’s blood glucose levels to determine effectiveness of canagliflozin therapy. Be aware that canagliflozin can increase urinary glucose excretion, leading to positive urine glucose tests, and should not be used to monitor glucose levels in patients with diabetes mellitus. Assess patient also receiving insulin or insulin secretagogues for hypoglycemia.
WARNING: Monitor patient closely for ketoacidosis that may occur despite the patient having type 2 diabetes and even may be present even if a blood glucose level is less than 250 mg/dl. If signs and symptoms occur such as dehydration, fruity odor to breath, malaise, nausea, shortness of breath, and vomiting, notify prescriber and expect drug to be discontinued. Provide supportive care, as ordered.
  • Be aware that patients with a history of genital mycotic infections, as well as uncircumcised males, are at greater risk for developing genital mycotic infections.
WARNING: Report immediately signs and symptoms of necrotizing fasciitis of the perineum (Fournier’s gangrene), a rare but serious and life-threatening necrotizing infection that has been linked to canagliflozin therapy. Report patient’s complaints of erythema, pain or tenderness, or swelling in the genital or perineal area, along with fever or malaise, as treatment requires urgent surgical intervention along with immediate broad-spectrum antibiotic therapy. If confirmed, expect canagliflozin to be discontinued and an alternative treatment for glycemic control prescribed.
  • Monitor patient’s lipid levels and expect to treat if an elevation occurs.
WARNING: Assess patient for hypersensitivity reactions such as angioedema and generalized urticaria, especially within hours to days after canagliflozin therapy is begun. The hypersensitivity reaction can become severe, causing anaphylaxis. If hypersensitivity to canagliflozin occurs, expect drug to be discontinued and provide supportive care as ordered.


  • Institute safety precautions to prevent falls because drug may increase risk of falls leading to bone fracture. The risk of bone fracture may occur as early as 12 weeks after therapy is begun.
  • Be aware that canagliflozin has been linked to an increase in foot and leg amputations in patients receiving the drug. Assess patient’s feet and legs regularly for any abnormalities and notify prescriber immediately if present. Be aware that patients may be at higher risk of lower-limb amputation if they have had diabetic foot sores or ulcers, have had blocked or narrowed blood vessels (usually in leg), have had damage to the nerves (neuropathy) in the leg, or have a history of amputation, heart disease, or are at risk for heart disease. Know that canagliflozin may be discontinued if abnormalities develop.

PATIENT TEACHING
    • Instruct patient to take canagliflozin before the first meal of the day. Tell her that if a dose is missed, she should take it as soon as she remembers unless it is almost time for the next dose. Then patient should skip the missed dose and take his normal dose of canagliflozin at the regular time. He should never double the dose.
    • Urge patient not to skip doses or increase dosage without consulting prescriber. However, tell the patient to notify the prescriber if he is unable to take a normal amount of daily fluids due to illness or fasting or experiences an excessive loss of fluids from excessive perspiration or gastrointestinal illnesses, as the drug may need to be temporarily withheld.
    • Emphasize the importance of reporting signs of hypoglycemia, such as anxiety, confusion, dizziness, excessive sweating, headache, and nausea.
    • Tell the patient to carry identification indicating that he has diabetes.
    • Teach the patient how to monitor his blood glucose level. Advise patient with diabetes mellitus not to use urine glucose tests to monitor her glycemic control, as the drug will cause a false positive result. Review signs and symptoms of ketoacidosis with the patient and urge her to seek immediate medical attention, if present, even if their blood glucose level is less than 250 mg/dl.
    • Inform the patient that canagliflozin is not a substitute for diet and exercise management.
    • Inform the patient that the drug may increase his risk for bone fractures and take safety precautions to prevent falls.
    • Advise the patient to avoid direct sunlight and to wear sunscreen when outdoors.
    • Instruct patient to notify prescriber right away if he notices any new pain or tenderness, sores or ulcers, or symptoms of infections in his feet or legs. Tell the patient this is very important because canagliflozin therapy increases the risk of lower-limb amputations.
    • Advise patient to seek medical care promptly if pain or tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum occurs, along with a fever above 38°C (100.4°F) or malaise develops.

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