Brand name: Invokana
Drug class: Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Antidiabetic agent; sodium-glucose cotransporter 2 (SGLT2) inhibitor.

Uses for Canagliflozin

Type 2 Diabetes Mellitus

Glycemic Control

Used as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus.

Used in combination with other antidiabetic agents (e.g., metformin, a sulfonylurea, a peroxisome proliferator-activated receptor_γ [PPAR_γ] agonist [thiazolidinedione], dipeptidyl peptidase-4 [DPP-4] inhibitor) or insulin as an adjunct to diet and exercise in patients with type 2 diabetes mellitus who have not achieved adequate glycemic control.

Commercially available as a single entity preparation and in fixed combination with immediate- or extended-release metformin hydrochloride (Invokamet or Invokamet XR); use the fixed combination when treatment with both drugs is appropriate.

Guidelines from the American Diabetes Association (ADA) and other experts generally recommend the use of SGLT2 inhibitors and/or glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes and established/high risk of atherosclerotic cardiovascular disease (ASCVD), heart failure, and/or chronic kidney disease. When selecting treatment regimen, consider factors such as cardiovascular and renal comorbidities, drug efficacy and adverse effects, hypoglycemic risk, presence of overweight or obesity, cost, access, and patient preferences. Weight management should be included as a distinct treatment goal and other healthy lifestyle behaviors should also be considered.

Not indicated for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

Not indicated to improve glycemic control in type 2 diabetes mellitus in patients with eGFR <30 mL/minute per 1.73 m².

Reduction in Risk of Major Adverse Cardiovascular Events

Used to reduce the risk of major cardiovascular events (e.g., cardiovascular death, nonfatal MI, nonfatal stroke) in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Some SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin) have demonstrated cardiovascular risk reduction benefits in patients with type 2 diabetes mellitus and established ASCVD (or high risk of ASCVD). In addition to lowering blood glucose, SGLT2 inhibitors appear to modify nonglycemic cardiovascular risk factors such as blood pressure, body weight, adiposity, and arterial stiffness.

For the treatment of patients with type 2 diabetes mellitus and established ASCVD (or high risk of ASCVD), current clinical practice guidelines generally recommend the use of an SGLT2 inhibitor with proven efficacy in cardiovascular outcomes trials.

Beneficial Effects on Renal Function and Cardiovascular Morbidity and Mortality in Diabetic Nephropathy

Used to reduce the risk of end-stage renal disease (ESRD), doubling of S_cr, cardiovascular death, and hospitalization for heart failure in adult patients with type 2 diabetes mellitus and diabetic nephropathy with albuminuria exceeding 300 mg/day.

Some SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin) have demonstrated beneficial effects on renal function in patients with type 2 diabetes mellitus and chronic kidney disease.

For the treatment of patients with type 2 diabetes mellitus and CKD, current clinical practice guidelines generally recommend the use of an SGLT2 inhibitor with proven benefit in reducing adverse renal outcomes.

Canagliflozin Dosage and Administration

General

Pretreatment Screening

• Assess renal function.

• Assess volume status; volume depletion should be corrected prior to initiation.

Patient Monitoring

• Assess renal function as clinically indicated.

• Monitor for signs and symptoms of volume depletion.

• Monitor for signs and symptoms of urinary tract and genital mycotic infection.

• Monitor for infections or ulcers of the lower limbs.

Other General Considerations

• Hold canagliflozin for at least 3 days, if possible, prior to major surgery or procedures requiring prolonged fasting. Resume therapy once patient is clinically stable and has resumed oral intake.

Administration

Oral Administration

Commercially available as single-entity tablets or in fixed combination with immediate- and extended-release metformin hydrochloride.

Canagliflozin: Administer once daily before the first meal of the day.

Fixed combination of canagliflozin and immediate-release metformin hydrochloride: Administer twice daily with meals.

Fixed combination of canagliflozin and extended-release metformin hydrochloride: Administer once daily with the morning meal; swallow tablet whole and do not crush, chew, or cut.

If a dose of canagliflozin is missed, take missed dose as soon as it is remembered followed by resumption of regular schedule. If missed dose is not remembered until the time of the next dose, skip missed dose and resume regular schedule; do not double dose to replace a missed dose.

Dosage

Dosage of canagliflozin expressed in terms of anhydrous canagliflozin.

Adults

Type 2 Diabetes Mellitus

Canagliflozin Monotherapy

Oral

Initially, 100 mg once daily, taken before first meal of the day.

If initial dosage well tolerated and additional glycemic control required, increase dosage to 300 mg once daily in patients with an eGFR ≥60 mL/minute per 1.73 m².

Canagliflozin/Immediate-release Metformin Hydrochloride Fixed-combination Therapy

Oral

Individualize dosage based on patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Patients not currently receiving treatment with either canagliflozin or metformin hydrochloride: Initially, 50 mg of canagliflozin and 500 mg of immediate-release metformin hydrochloride (Invokamet) twice daily.

Patients currently receiving metformin hydrochloride: Initially, 100 mg of canagliflozin and a total daily metformin hydrochloride dosage similar to the patient's existing dosage, administered in 2 divided doses. In patients currently receiving an evening dose of extended-release metformin hydrochloride, skip last dose prior to initiating therapy with fixed combination of canagliflozin and metformin hydrochloride the following morning.

Patients currently receiving canagliflozin: Initially, same daily dosage of canagliflozin and metformin hydrochloride 1 g daily, administered in 2 divided doses.

Patients currently receiving canagliflozin and metformin hydrochloride: Initially, same daily dosage of canagliflozin and a total daily metformin hydrochloride dosage similar to patient's existing dosage, administered in 2 divided doses. In patients currently receiving an evening dose of extended-release metformin hydrochloride, skip last dose prior to initiating therapy with fixed combination of canagliflozin and metformin hydrochloride the following morning.

Canagliflozin/Extended-release Metformin Hydrochloride Fixed-combination Therapy

Oral

Individualize dosage based on the patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Patients not currently receiving treatment with either canagliflozin or metformin hydrochloride: Initially, 100 mg of canagliflozin and 1 g of extended-release metformin hydrochloride (Invokamet XR) once daily.

Patients currently receiving metformin hydrochloride: Initially, 100 mg of canagliflozin and a total daily metformin hydrochloride dosage similar to the patient's existing dosage once daily. In patients currently receiving an evening dose of extended-release metformin hydrochloride, skip last dose prior to initiating therapy with fixed combination of canagliflozin and metformin hydrochloride the following morning.

Patients currently receiving canagliflozin: Initially, same daily dosage of canagliflozin and 1 g metformin hydrochloride once daily.

Patients currently receiving canagliflozin and metformin hydrochloride: Initially, same daily dosage of canagliflozin and a total daily metformin hydrochloride dosage similar to patient's existing dosage once daily. In patients currently receiving an evening dose of extended-release metformin hydrochloride, skip last dose prior to initiating therapy with fixed combination of canagliflozin and metformin hydrochloride the following morning.

Dosage Modification for Drug Interactions

Canagliflozin Monotherapy

Oral

Patients with an eGFR ≥60 mL/minute per 1.73 m² receiving concurrent therapy with a uridine diphosphate-glucuronosyltransferase (UGT) enzyme inducer (e.g., phenobarbital, phenytoin, rifampin, ritonavir): Increase canagliflozin dosage to 200 mg once daily in patients tolerating 100 mg once daily. May increase dosage to 300 mg once daily in patients who require additional glycemic control and are currently tolerating 200 mg once daily.

Canagliflozin/Immediate-release Metformin Hydrochloride Fixed-combination Therapy

Oral

Patients currently receiving both canagliflozin and metformin hydrochloride with an eGFR ≥60 mL/minute per 1.73 m² and concurrent therapy with a UGT enzyme inducer: Increase total daily dosage of canagliflozin to 200 mg in patients currently tolerating 100 mg daily. May increase total daily dosage of canagliflozin to 300 mg in patients who require additional glycemic control and are currently tolerating 200 mg daily.

Canagliflozin/Extended-release Metformin Hydrochloride Fixed-combination Therapy

Oral

Patients with an eGFR ≥60 mL/minute per 1.73 m² receiving concurrent therapy with a UGT enzyme inducer: Increase total daily dosage of canagliflozin to 200 mg in patients who are tolerating 100 mg daily. May increase total daily dosage of canagliflozin to 300 mg in patients who require additional glycemic control and are currently tolerating 200 mg daily.

Special Populations

Hepatic Impairment

Canagliflozin Monotherapy

Mild or moderate hepatic impairment: No dosage adjustment necessary.

Severe hepatic impairment: Data lacking; not recommended.

Canagliflozin/Metformin Hydrochloride Fixed-combination Therapy

Use of the fixed-combination preparation of canagliflozin and metformin hydrochloride not recommended.

Renal Impairment

Canagliflozin Monotherapy

eGFR ≥60 mL/minute per 1.73 m²: No dosage adjustment necessary.

eGFR <60 mL/minute per 1.73 m² receiving concurrent therapy with UGT enzyme inducer: Increase canagliflozin dosage to 200 mg once daily in patients currently tolerating 100 mg daily. Consider adding another antihyperglycemic agent in such patients who require additional glycemic control.

eGFR 30 to <60 mL/minute per 1.73 m²: Do not exceed 100 mg once daily.

eGFR <30 mL/minute per 1.73 m²: Do not initiate in patients being treated for glycemic control. In patients already receiving therapy whose eGFR decreases to <30 mL/minute per 1.73 m² and who have albuminuria >300 mg/day, may continue therapy at 100 mg once daily.

Canagliflozin/Metformin Hydrochloride Fixed-combination Therapy

eGFR 45 to <60 mL/minute per 1.73 m²: Do not exceed 100 mg of canagliflozin component daily.

eGFR of <60 mL/minute per 1.73 m² receiving concurrent therapy with UGT enzyme inducer: May increase total daily dosage of canagliflozin to a maximum of 200 mg in patients who are tolerating 100 mg daily.

eGFR 30 to <45 mL/minute per 1.73 m² : Do not initiate. In patients already receiving therapy, assess benefits and risks of continuing canagliflozin and metformin hydrochloride; limit total daily dosage of canagliflozin to 100 mg daily.

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue use.

Geriatric Patients

Canagliflozin Monotherapy

No specific dosage recommendations.

Canagliflozin/Metformin Hydrochloride Fixed-combination Therapy

Monitor renal function more frequently in geriatric patients after initiating fixed-combination preparation; adjust dosage according to patient's renal function.

Cautions for Canagliflozin

Contraindications

• History of serious hypersensitivity reaction (e.g., anaphylaxis, angioedema) to canagliflozin.

Warnings/Precautions

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Ketoacidosis requiring hospitalization reported in patients with type 1 or type 2 diabetes mellitus receiving SGLT2 inhibitors; occurred in some cases without markedly elevated blood glucose concentrations (e.g., <250 mg/dL).

Evaluate for presence of ketoacidosis in patients experiencing severe metabolic acidosis regardless of the patient's blood glucose concentration; discontinue canagliflozin and initiate appropriate treatment to correct acidosis if confirmed. Monitor patient for resolution prior to restarting the drug.

Prior to initiating canagliflozin therapy, consider factors that may predispose patients to ketoacidosis (e.g., pancreatic disorders [e.g., history of pancreatitis, pancreatic surgery] insulin deficiency, reduced caloric intake, acute febrile illness, ketogenic diet, surgery, volume depletion, alcohol abuse). Risk factors for development of ketoacidosis should be resolved prior to initiation.

Educate patients on signs and symptoms of ketoacidosis and instruct them to discontinue canagliflozin and seek medical attention immediately if signs and symptoms occur.

Withhold canagliflozin if possible in temporary clinical situations that may predispose patients to ketoacidosis; resume therapy once patient is clinically stable and able to resume oral intake. For patients who undergo surgery or procedures associated with prolonged fasting, withhold canagliflozin for ≥3 days if possible. Resume therapy once patient is clinically stable and able to resume oral intake.

Consider monitoring urine and/or plasma ketones in patients who may be at risk for ketoacidosis, if indicated by clinical situation.

Lower Limb Amputation

Analysis of data from clinical studies evaluating canagliflozin (Canagliflozin Cardiovascular Assessment Study [CANVAS] and CANVAS-R) revealed a twofold increase in leg and foot amputations, mostly affecting the toes and midfoot, in patients receiving the drug. Patients with baseline history of prior amputation, peripheral vascular disease, or neuropathy were at greatest risk for amputation. Most common precipitating medical events leading to amputation were lower limb infections, gangrene, and diabetic foot ulcers.

Prior to initiating canagliflozin therapy, consider factors that may predispose patients to the need for amputation (e.g., history of amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers).

Monitor patients for the presence of infection (including osteomyelitis), new pain or tenderness, or sores or ulcers involving the lower limbs; discontinue canagliflozin if such complications occur. Counsel patients on importance of preventative foot care.

Volume Depletion

May cause intravascular volume contraction. Symptomatic hypotension or acute transient changes in serum creatinine reported. Postmarketing reports of acute kidney injury that are likely related to volume depletion, some requiring hospitalization or dialysis, reported in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including canagliflozin.

Patients with impaired renal function (eGFR <60 mL/minute per 1.73 m²), geriatric patients, or patients receiving loop diuretics may be at increased risk.

Assess and correct intravascular volume prior to initiating canagliflozin in such patients. Monitor patients for sign and symptoms of hypotension after initiating therapy.

Urosepsis and Pyelonephritis

May increase the risk of serious urinary tract infections (e.g., urosepsis, pyelonephritis) requiring hospitalization, including intensive care or dialysis.

Prior to initiating canagliflozin therapy, consider patient factors that may predispose to serious urinary tract infections (e.g., history of difficulty urinating; infection of the bladder, kidneys, or urinary tract).

Monitor patients for urinary tract infections and initiate treatment if indicated.

Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues

When adding canagliflozin to therapy with an insulin secretagogue (e.g., a sulfonylurea) or insulin, consider reducing dosage of the concomitant insulin secretagogue or insulin to reduce the risk of hypoglycemia.

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)

Necrotizing fasciitis of the perineum (Fournier's gangrene), a rare but serious and life-threatening bacterial infection requiring urgent surgical intervention, reported during postmarketing surveillance in males and females with type 2 diabetes mellitus receiving an SGLT2 inhibitor.

Assess for necrotizing fasciitis in patients receiving canagliflozin who develop pain or tenderness, erythema, or swelling in the genital or perineal area, in addition to fever or malaise. Discontinue canagliflozin if Fournier's gangrene suspected; initiate treatment with broad-spectrum antibiotics and perform surgical debridement if necessary. Monitor blood glucose concentrations closely; initiate alternative antidiabetic agents to maintain glycemic control.

Genital Mycotic Infections

May increase risk of genital mycotic infections in males (e.g., balanoposthitis, candidal balanitis) and females (e.g., vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginitis). Patients with a history of genital mycotic infections and uncircumcised males more likely to develop such infections.

Monitor patients for genital mycotic infections and institute appropriate treatment if these infections occur.

Hypersensitivity Reactions

Hypersensitivity reactions, including angioedema and anaphylaxis, reported. Discontinue drug if hypersensitivity reaction occurs; institute appropriate treatment, and monitor patients until signs and symptoms resolve.

Bone Fracture

Increased risk of bone fracture. Fractures observed as early as 12 weeks after initiation of canagliflozin treatment; more likely to affect the distal portion of upper and lower extremities and be associated with minor trauma (e.g., falls from no greater than standing height).

Dose-related decreases in bone mineral density also observed in older adults (mean age: 64 years) receiving canagliflozin for 2 years.

Consider factors that contribute to fracture risk and counsel patients about such factors prior to initiating canagliflozin therapy.

Laboratory Test Interference

SGLT2 inhibitors, including canagliflozin, increase urinary glucose excretion and will result in false-positive urine glucose tests. Manufacturer states that 1,5-anhydroglucitol assay is unreliable for monitoring glycemic control in patients taking SGLT2 inhibitors. Alternate methods of monitoring glycemic control should be used.

Use of Fixed Combinations

When used in fixed combination with other drugs (e.g., metformin), consider the cautions, precautions, contraindications, and interactions associated with the concomitant agent(s) in addition to those associated with canagliflozin.

Specific Populations

Pregnancy

Insufficient data to evaluate drug-associated risk of adverse developmental outcomes. Studies in animals indicate that canagliflozin use during pregnancy may affect renal development and maturation, especially during the second and third trimesters.

Poorly controlled diabetes mellitus during pregnancy carries risk to mother and fetus; however, canagliflozin not recommended for use in the second or third trimesters of pregnancy.

Lactation

No data on presence of canagliflozin in human milk, effects on breast-fed child, or effects on milk production. Distributed into milk in rats. Not recommended for use in women who are breast-feeding.

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.

Geriatric Use

Reduced efficacy compared with younger patients as evidenced by smaller reductions in HbA_1c. Patients ≥65 years of age more likely to experience certain adverse effects related to reduced intravascular volume (e.g., hypotension, postural dizziness, orthostatic hypotension, syncope, dehydration), particularly with canagliflozin 300 mg daily; prominent increase in incidence of these adverse effects observed in patients ≥75 years of age in clinical trials.

Hepatic Impairment

Canagliflozin: Not studied in severe hepatic impairment (Child-Pugh class C); use not recommended. Differences in pharmacokinetics in patients with mild or moderate hepatic impairment compared with individuals with normal hepatic function were not considered clinically important.

Fixed combination of canagliflozin and metformin hydrochloride: Use not recommended.

Renal Impairment

Canagliflozin: Dosage reduction required for patients with an eGFR <60 mL/minute per 1.73 m². Assess renal function prior to initiation of canagliflozin and periodically thereafter. Patients with moderate renal impairment had less overall glycemic efficacy; those treated with 300 mg per day had increases in serum potassium. Patients with renal impairment using canagliflozin for glycemic control also may be more likely to experience hypotension and may be at higher risk for acute kidney injury.

Fixed combination of canagliflozin and metformin hydrochloride: Use contraindicated in patients with eGFR <30 mL/minute per 1.73 m².

Common Adverse Effects

Most common adverse effects (≥5%): female genital mycotic infections, urinary tract infection, increased urination.

Drug Interactions

Major metabolic elimination pathway is O-glucuronidation; mainly glucuronidated by uridine diphosphoglucuronosyltransferase (UGT) isoenzymes UGT1A9 and UGT2B4.

P-glycoprotein substrate and weak P-glycoprotein inhibitor. Also a substrate of multidrug resistance-associated protein 2 (MRP2).

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Minimal metabolism (approximately 7%) by CYP3A4. Did not induce CYP-450 isoenzymes 3A4, 2C9, 2C19, 2B6, or 1A2 in cultured human hepatocytes; did not inhibit CYP1A2, 2A6, 2C19, 2D6, or 2E1 but weakly inhibits CYP2B6, 2C8, 2C9, and 3A4 in human hepatic microsomes.

Drug Affecting Efflux Transport Systems

Concomitant use of canagliflozin with an inducer of UGT enzymes may decrease efficacy of canagliflozin.

If UGT enzyme inducer (e.g., phenobarbital, phenytoin, rifampin, ritonavir) is used concomitantly with canagliflozin in patients with eGFR ≥60 mL/minute per 1.73 m², increase and titrate canagliflozin dosage according to tolerance in patients who require additional glycemic control.

If UGT enzyme inducer (e.g., phenobarbital, phenytoin, rifampin, ritonavir) is used concomitantly with canagliflozin in patients with eGFR <60 mL/minute per 1.73 m², increase dosage of canagliflozin according to tolerance to maximum of 200 mg; consider adding another antidiabetic agent in patients who require additional glycemic control.

Specific Drugs and Laboratory Tests

Canagliflozin Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations usually attained within 1–2 hours after oral dosing.

Mean absolute oral bioavailability: approximately 65%.

Bioequivalence study: Fixed-combination tablets of canagliflozin and immediate-release metformin hydrochloride (Invokamet) are bioequivalent to individual tablets of canagliflozin and metformin hydrochloride administered concomitantly in equivalent doses under fed conditions.

Food

Administration with high-fat meal had no effect on canagliflozin pharmacokinetics. However, based on the drug's potential to reduce postprandial plasma glucose excursions due to delayed intestinal glucose absorption, administer canagliflozin with first meal of the day.

Specific Populations

Mild hepatic impairment (Child-Pugh class A): AUC and peak plasma concentration increased by 10 and 7%, respectively, compared with normal hepatic function.

Moderate hepatic impairment (Child-Pugh class B): AUC increased by 11% and peak plasma concentration decreased by 4% compared with normal hepatic function.

Mild renal impairment (eGFR 60 to <90 mL/minute per 1.73 m²): AUC increased by 15%, compared with healthy individuals following a single 200-mg dose of the drug.

Moderate renal impairment (eGFR 30 to <60 mL/minute per 1.73 m²): AUC increased by 29% compared with healthy individuals following single 200-mg dose of drug.

Severe renal impairment (eGFR <30 mL/minute per 1.73 m²): AUC increased by 53% compared with healthy individuals following single 200-mg dose of drug.

Distribution

Extent

Extensively distributes into tissues.

Plasma Protein Binding

99% (mainly to albumin).

Specific Populations

Renal or hepatic impairment does not meaningfully alter plasma protein binding.

Elimination

Metabolism

Metabolized principally via O-glucuronidation by UGT1A9 and UGT2B4 to inactive metabolites.

Elimination Route

41.5, 7, and 3% recovered in feces as canagliflozin, a hydroxylated metabolite, and an O-glucuronide metabolite, respectively.

33% excreted in urine; 30.5% as O-glucuronide metabolite and <1% as unchanged drug.

Half-life

Terminal elimination half-life: 10.6 and 13.1 hours for single doses of 100 and 300 mg, respectively.

Stability

Storage

Oral

Tablets

Canagliflozin: 20—25°C (may be exposed to 15–30°C).

Fixed combination of canagliflozin and metformin hydrochloride: 20–25°C (may be exposed to 15–30°C). Store and dispense in original container. May store in pill box for ≤30 days.

Actions

• Inhibits SGLT2, a transporter expressed in proximal renal tubules and responsible for majority of reabsorption of filtered glucose from tubular lumen.

• Reduces reabsorption of filtered glucose and lowers the renal threshold for glucose in a dose-dependent manner, leading to increased urinary glucose excretion.

• Increases glucose excretion independent of insulin secretion.

• May delay oral glucose absorption through transient inhibition of SGLT1 in the intestinal lumen.

• Increases delivery of sodium to the distal tubule by blocking SGLT2-dependent glucose and sodium reabsorption. This effect may increase tubuloglomerular feedback and reduce intraglomerular pressure.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Medication Guide) before initiating therapy and each time the drug is dispensed.

• When canagliflozin is used in fixed combination with other drugs, inform patients of important cautionary information about the concomitant agent(s).

• Advise patients of the potential risks and benefits of canagliflozin and of alternative therapies.

• Advise patients of the importance of not using canagliflozin in type 1 diabetes mellitus.

• Inform patients that if a dose of canagliflozin or the fixed combination of canagliflozin and metformin hydrochloride is missed, it should be taken as soon as it is remembered; if it is almost time for the next dose, the patient should skip the missed dose and take the drug at the next regularly scheduled time. Advise patients not to take 2 doses of the drug at the same time.

• Inform patients that ketoacidosis, which can be a life-threatening condition and is sometimes associated with illness or surgery among other risk factors, has been reported with canagliflozin therapy. Educate patients and their caregivers about the signs and symptoms of ketoacidosis (e.g., tachypnea or hyperventilation, anorexia, abdominal pain, nausea, vomiting, lethargy, mental status change) and instruct patients to discontinue canagliflozin and seek medical attention immediately should they experience any such signs or symptoms. Advise patients to use a ketone dipstick to check for ketones in their urine (when possible) if symptoms of ketoacidosis occur, even if blood glucose is not elevated (i.e., <250 mg/dL).

• Inform patients that canagliflozin therapy is associated with an increased risk of the need for lower limb amputation, which may be higher in some patients, including those with peripheral vascular disease, neuropathy, diabetic foot ulcers, or a history of amputation. Counsel patients on the importance of routine preventative foot care. Advise patients to monitor for new pain or tenderness, sores or ulcers, or infections involving the leg or foot and to seek medical attention immediately should they experience such signs or symptoms.

• Inform patients that symptomatic hypotension may occur with canagliflozin and to report such symptoms to their clinicians. Inform patients that canagliflozin-induced dehydration may increase the risk of hypotension and that patients should maintain adequate fluid intake.

• Inform patients that hypoglycemia has been when reported when canagliflozin is used with insulin or insulin secretagogues. Educate patients and caregivers on the signs and symptoms of hypoglycemia.

• Inform patients of the potential for urinary tract infections, which may be serious, with canagliflozin therapy. Advise patients of the signs and symptoms of urinary tract infection and the need to contact a clinician promptly if such signs and symptoms occur.

• Inform patients that necrotizing infections of the perineum (Fournier's gangrene) have occurred with canagliflozin therapy. Advise patients to seek prompt medical attention if they experience any symptoms of tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, occurring with a fever above 38°C or malaise.

• Inform patients that yeast infection may occur (e.g., vulvovaginitis, balanitis, balanoposthitis). Inform female patients of the signs and symptoms of vaginal yeast infections (e.g., vaginal discharge, odor, itching) and male patients of the signs and symptoms of balanitis or balanoposthitis (e.g., rash or redness of the glans or foreskin of the penis). Advise patients of treatment options and when to seek medical advice.

• Inform patients of the risk of serious hypersensitivity reactions, such as rash, urticaria, angioedema, and anaphylaxis. Advise patients to immediately report any signs or symptoms suggestive of allergic reaction, and to discontinue canagliflozin and inform their clinician promptly.

• Inform patients that bone fractures have been reported in patients treated with canagliflozin therapy and provide information about factors contributing to fracture risk.

• Advise females of reproductive potential and pregnant women of the possible risk to a fetus with canagliflozin therapy. Instruct females of reproductive potential to report pregnancy to their clinician as soon as possible. Advise women that breastfeeding is not recommended during canagliflozin therapy.

• Inform patients that due to the mechanism of action of canagliflozin, patients taking the drug will test positive for glucose in their urine. Inform patients that urine glucose tests should not be used to monitor glycemic status while taking canagliflozin; use alternative methods to monitor glycemic control.

• Inform patients of the importance of seeking medical advice promptly during periods of stress such as fever, trauma, infection, or surgery as drug dosage requirements may change.

• Advise patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and glycosylated hemoglobin (hemoglobin A_1c; HbA_1c) testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes complications.

• Inform patients of the importance of taking canagliflozin exactly as directed by clinician. Advise patients not to discontinue canagliflozin without discussing it with the prescribing clinician.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription (e.g., diuretics, rifampin, phenytoin, phenobarbital, ritonavir, digoxin) and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

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