canagliflozin

kan-a-gli-FLOE-zin

Therapeutic Classification: antidiabetics

Pharmacologic Classification: sodium-glucose co-transporter 2 (SGLT2) inhibitors

BEERS REMS

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.
To reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular death, and hospitalization for HF in patients with type 2 diabetes mellitus and diabetic nephropathy with albuminuria >300 m g/day.

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 effects:

Improved glycemic control.
Reduction in risk of cardiovascular death, nonfatal MI, and nonfatal stroke.
Reduction in risk of ESKD, doubling of serum creatinine, cardiovascular death, and HF hospitalizations.

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

Distribution: Extensive tissue distribution.

Protein Binding: 99%

Metabolism/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

(effects on A1C)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	unknown	24 hr

Contraindicated in:

Hypersensitivity;
Type 1 diabetes;
Severe hepatic impairment;
Lactation: Lactation.

Use Cautiously in:

History of pancreatitis, pancreatic surgery, reduced caloric intake due to illness or surgery, surgical procedures or alcohol abuse (↑ risk of ketoacidosis);
Hypovolemia, chronic kidney disease (eGFR <60 mL/min/1.73 m²), or concurrent use of loop diuretics (↑ risk of volume depletion or hypotension);
Previous amputation, peripheral vascular disease, neuropathy, or diabetic foot infection (↑ risk of lower limb amputation);
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 in children;
Geri: Appears on Beers list. Older adults may have risk of urogenital infections (especially women in the 1st mo of treatment) and euglycemic diabetic ketoacidosis. Use with caution in older adults.

CV: hypotension

Endo: hypoglycemia (↑ with other medications)

F and E: hypermagnesemia, hyperphosphatemia, KETOACIDOSIS, thirst

GI: abdominal pain, constipation, nausea

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

Metab: hyperlipidemia

MS: bone fractures, lower limb amputation

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS OR ANGIOEDEMA)

Drug-drug:

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 loop diuretics, may ↑ risk of hypovolemia and hypotension.
May ↓ lithium levels and effectiveness.

PO (Adults ): 100 mg once daily initially, may ↑ to 300 mg once daily; Concurrent use of UGT inducers (phenobarbital, phenytoin, rifampin, ritonavir): If patient tolerating canagliflozin 100 mg once daily, ↑ to 200 mg once daily; if patient tolerating canagliflozin 200 mg once daily and requires addition glycemic control, ↑ to 300 mg once daily.

Renal Impairment

PO (Adults ): eGFR 30–<60 mL/min/1.73 m²: 100 mg once daily. eGFR <30 mL/min/1.73 m²: Initiation of therapy not recommended; patients with albuminuria >300 m g/day who are already receiving therapy may continue with 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, cardiovascular death, and hospitalization for HF. Concurrent use of UGT inducers (phenobarbital, phenytoin, rifampin, ritonavir) and eGFR <60 mL/min/1.73 m²: If patient tolerating canagliflozin 100 mg once daily, ↑ to 200 mg once daily; if patient requires additional glycemic control, consider adding another antihyperglycemic agent.

Tablets: 100 mg; 300 mg
In combination with: metformin (Invokamet); metformin XR (Invokamet XR). See Appendix [not included in this PDA edition].

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.

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.

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, preventative foot care, 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 occurs.
Advise patient to notify health care professional of medication regimen before treatment or surgery. Holding doses for at least 3 days before surgery may be required.
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.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during therapy; especially avoid canagliflozin during the 2nd and 3rd trimesters. Advise patient to notify health care professional if pregnancy is planned or suspected.

Improved hemoglobin A1C and glycemic control in adults with Type II diabetes.
Reduction in risk of cardiovascular death, nonfatal MI, and nonfatal stroke.
Reduction in risk of ESKD, doubling of serum creatinine, cardiovascular death, and HF hospitalizations.

Invokana

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US Brand Names ⬆