Indicated for:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

• To reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD).

• To reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day.

INVOKANA is not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

INVOKANA is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m². INVOKANA is likely to be ineffective in this setting based upon its mechanism of action.

Lactic acidosis is a rare but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as renal impairment, sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure.

Infection of the genitals and area around the genitals called necrotizing fasciitis of the perineum or Fournier’s gangrene.

INVOKANA increases the risk of genital mycotic infections. Patients with a history of genital mycotic infections and uncircumcised males were more likely to develop genital mycotic infections.

An increased risk of lower limb amputations associated with INVOKANA use versus placebo was observed. Lower limb infections, gangrene, and diabetic foot ulcers were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy.

Before initiating INVOKANA, consider factors in the patient history that may predispose to the need for amputations, such as a history of prior amputation, peripheral vascular disease, neuropathy and diabetic foot ulcers. Counsel patients about the importance of routine preventative foot care. Monitor patients receiving INVOKANA for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue INVOKANA if these complications occur.

INVOKANA causes intravascular volume contraction and can cause acute kidney injury. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors, including INVOKANA. Increases in serum creatinine and decreases in estimated GFR may also be observed with initiation of INVOKANA.

Before initiating INVOKANA, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs).

The dose of INVOKANA is limited to 100 mg once daily in patients with moderate renal impairment with an eGFR of 45 to less than 60 mL/min/1.73 m².

Initiation of INVOKANA is not recommended in patients with an eGFR less than 45 mL/min/1.73 m².

Use of INVOKANA is not recommended when eGFR is persistently less than 45 mL/min/1.73 m².

INVOKANA is contraindicated in patients on dialysis.

INVOKANA is not recommended in patients with severe hepatic impairment.

There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including INVOKANA.

An increased risk of bone fracture, occurring as early as 12 weeks after treatment initiation, was observed in patients using INVOKANA.

Hypersensitivity reactions, including angioedema and anaphylaxis, have been reported with INVOKANA.

INVOKANA can cause intravascular volume contraction which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been post-marketing reports of acute kidney injury which are likely related to volume depletion, some requiring hospitalizations and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including INVOKANA.

Fatal cases of ketoacidosis have been reported in patients taking INVOKANA. Before initiating INVOKANA, consider factors in the patient history that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. 

INVOKANA can lead to hyperkalemia.

INVOKANA can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue.

For patients who undergo scheduled surgery, consider temporarily discontinuing INVOKANA for at least 3 days prior to surgery.

Co-administration of canagliflozin with rifampin, a nonselective inducer of several UGT enzymes, including UGT1A9, UGT2B4, decreased canagliflozin area under the curve (AUC) by 51%.

For patients with eGFR 60 mL/min/1.73 m² or greater, if an inducer of UGTs (e.g., rifampin, phenytoin, phenobarbital, ritonavir) is co-administered with INVOKANA, increase the dose to 200 mg (taken as two 100 mg tablets) once daily in patients currently tolerating INVOKANA 100 mg. The dose may be increased to 300 mg once daily in patients currently tolerating INVOKANA 200 mg and who require additional glycemic control.For patients with eGFR less than 60 mL/min/1.73 m².

if an inducer of UGTs (e.g., rifampin, phenytoin, phenobarbital, ritonavir) is co-administered with INVOKANA, increase the dose to 200 mg (taken as two 100 mg tablets) once daily in patients currently tolerating INVOKANA 100 mg. Consider adding another antihyperglycemic agent in patients who require additional glycemic control.

There was an increase in the AUC and mean peak drug concentration (Cmax) of digoxin (20% and 36%, respectively) when co-administered with INVOKANA 300 mg.

Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control.

Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

Based on animal data showing adverse renal effects, INVOKANA is not recommended during the second and third trimesters of pregnancy.

Because of the potential for serious adverse reactions in a breastfed infant, advise women that use of INVOKANA is not recommended while breastfeeding.

GoToSource

• Use in patients under the age of 18. GoToSource

• Type 1 diabetes and diabetic ketoacidosis. GoToSource

Genital mycotic infections, urinary tract infections and pollakiuria (abnormal frequency of urination). GoToSource

Pancreatitis (inflammation of the pancreas). GoToSource

Increased risk of breast and bladder cancer. GoToSource 

Cerebrovascular accidents. GoToSource 

Kidney impairment, hypotension (low blood pressure), hyperkalemia (high potassium levels), hypoglycemia (low blood sugar) and hypersensitivity reactions. GoToSource 

Ketoacidosis (excess blood acids). GoToSource

Increased risk of bone fractures. GoToSource

Decreased bone mineral density. GoToSource 

Severe photosensitivity reactions. GoToSource 

Necrotizing fasciitis of the perineum or fournier’s gangrene (serious Infection in area around genitals). GoToSource

Leg and foot amputations. GoToSource

Lawsuits filed for diabetic ketoacidosis, kidney failure and fournier’s gangrene.