canagliflozin

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, acute febrile illness, 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 angiotensin receptor blockers);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children <18 yr (to ↓ risk of major adverse cardiovascular events in patients with type 2 diabetes mellitus and established cardiovascular disease or to ↓ risk of ESKD, doubling of serum creatinine, cardiovascular death, and hospitalization for HF in patients with type 2 diabetes mellitus and diabetic nephropathy with albuminuria >300 mg/day) or <10 yr (to improve glycemic control in type 2 diabetes mellitus);
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.

Adv. Reactions/Side Effects ⬆ ⬇

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 GANGRENE), UTI (including pyelonephritis), UROSEPSIS, vulvovaginal pruritus

Metab: hyperlipidemia

MS: bone fractures, lower limb amputation

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS OR ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

UGT inducers, including phenobarbital, phenytoin, rifampin, and ritonavir, may ↓ levels and effectiveness; ↑ dose may be required.
↑risk of hypoglycemia with insulin or insulin secretagogues; dose adjustments may be required.
May ↑ levels and risk of toxicity of digoxin; closely monitor digoxin levels.
↑risk of hyperkalemia with potassium-sparing diuretics or medications that interfere with the renin-angiotensin-aldosterone system.
Loop diuretics may ↑ risk of hypovolemia and hypotension.
May ↓ lithium levels and effectiveness.

Availability ⬆ ⬇

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

Route/Dosage ⬆ ⬇

Improvement in Glycemic Control in Type 2 Diabetes

PO (Adults and Children ≥10 yr): 100 mg once daily initially; may ↑ to 300 mg once daily if additional glycemic control needed; 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 and Children ≥10 yr): 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 mg/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.

Reduction in Risk of Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease or Reduction in Risk of End-Stage Kidney Disease, Doubling of Serum Creatinine, Cardiovascular Death, and Hospitalization for HF in Patients with Type 2 Diabetes Mellitus and Diabetic Nephropathy with Albuminuria >300 mg/day

PO (Adults ): 100 mg once daily initially; 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 mg/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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits proximal renal tubular sodium-glucose cotransporter 2 (SGLT2), which determines reabsorption of glucose from the tubular lumen. Inhibits reabsorption of glucose, lowers renal threshold for glucose, and ↑ 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.

Classifications ⬆ ⬇

Therapeutic Classification: antidiabetics

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

Pharmacokinetics ⬆ ⬇

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

Time/Action Profile ⬆ ⬇

(effects on A1c)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	unknown	24 hr

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.
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.
Explain to patient that canagliflozin helps control hyperglycemia but does not cure diabetes.
Encourage patient to follow prescribed diet, medication, preventative foot care, and exercise regimen to prevent hyperglycemia, hypoglycemia, and lower limb amputation.
Review signs and symptoms of hypoglycemia (pallor, shakiness, diaphoresis, headache, hunger, nausea), hyperglycemia, and ketoacidosis (nausea, vomiting, abdominal pain, malaise, dyspnea). If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 teaspoons of sugar, honey, or corn syrup dissolved in water and notify health care professional. If ketoacidosis occurs, instruct patient to discontinue canagliflozin and seek medical attention immediately.
Instruct patient in proper testing of blood glucose and urine ketones, especially during periods of stress, surgery, or illness. Inform patient that canagliflozin will cause a positive urine glucose test. Notify health care professional if significant changes occur.
Advise patient to discontinue canagliflozin and 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 >100.4°F or malaise, occur.
Advise patient to notify health care professional if signs or symptoms of yeast infection (vaginal odor, discharge, or itching; penile redness, itching, rash, pain, swelling, odor, or discharge) occur.
Advise patient to discontinue canagliflozin and 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 procedures that require prolonged fasting or surgery. Hold dose for ≥3 days before surgery. Restart canagliflozin when patient is medically stable and has resumed oral intake.
Inform patient of ↑ risk for UTIs, hypotension, and bone fractures, and discuss factors that may ↑ risk of these events.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception and avoid breastfeeding during therapy, especially during the 2nd and 3rd trimesters. Advise patient to notify health care professional if pregnancy is planned or suspected.

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Indications ⬇

Contraind./Precautions ⬆ ⬇