Invokana

What is Invokana?

Invokana, also known by its generic name canagliflozin, is a prescription medication used together with diet and exercise to help improve blood sugar control in adults with type 2 diabetes mellitus.

Invokana belongs to a class of medications called sodium-glucose cotransporter 2 (SGLT2) inhibitors. It works by helping the kidneys remove excess glucose from the body through the urine.

Invokana is also approved to help reduce the risk of certain cardiovascular complications, such as heart attack, stroke, or cardiovascular death, in adults with type 2 diabetes and established cardiovascular disease. In some patients with diabetic kidney disease, it may also help reduce the risk of kidney function decline, hospitalization for heart failure, and end-stage kidney disease.

Managing blood sugar levels may help lower the risk of diabetes-related complications such as kidney damage, nerve problems, vision loss, and cardiovascular disease.

Invokana is not indicated for the treatment of type 1 diabetes.

How does it work?

Invokana works by blocking a protein in the kidneys called sodium-glucose cotransporter 2 (SGLT2). This protein normally helps the body reabsorb glucose back into the bloodstream.

By blocking SGLT2, Invokana helps remove excess glucose through the urine, which lowers blood sugar levels in adults with type 2 diabetes.

This process works independently of insulin and may also help support heart and kidney health in certain patients with type 2 diabetes.

Side Effects

This drug is an effective tool for controlling blood sugar in people with type 2 diabetes mellitus. However, like all medications, it may cause side effects. It’s important to be aware of these potential side effects and understand the toll they may take on your body to manage them effectively if they occur.

Common Side Effects:

• Urinary tract infections
• Increased urination
• Yeast infections
• Vaginal itching
• Thirst
• Constipation
• Nausea
• Fatigue
• Weakness
• Skin sensitivity to sunlight
• Hypersensitivity reactions (including skin redness, rash, itching, hives, and swelling)
• Bone fractures
• Kidney problems

Serious Side Effects:

• Swelling, hives, difficulty breathing, swelling of your tongue, mouth, or throat
• Bloody or cloudy urine, decreased amount of urine, painful urination
• Loss of appetite, back pain, pain during intercourse, unusual tiredness or weakness
• Vaginal discharge, and weight gain
• Serious eye symptoms (sudden vision loss, blurred vision, eye pain or swelling, seeing halos around lights)
• Heart symptoms (fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; sudden dizziness, lightheadedness, or passing out)
• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, very stiff muscles, high fever, profuse sweating, or tremors

Warning:

• An approximately 2-fold increased risk of lower limb amputations has been observed in patients using Invokana. The most common amputations were those of the toe and midfoot; however, amputations involving the leg were also observed.

If you experience any of these side effects, especially the more serious ones, seek medical attention immediately. Always consult with your healthcare provider for more detailed information and guidance tailored to your specific health situation.

Warnings & Precautions

Lower Limb Amputation (FDA Boxed Warning)

In clinical trials, there was a higher risk of lower limb amputations in the group treated with Invokana compared to the group treated with placebo. This risk occurred at both the 100 mg and 300 mg doses. The most common amputations were those of the toe and midfoot, however, amputations of the leg also occurred. A few patients also had to undergo multiple amputations.

Patients with a history of previous amputation, peripheral vascular disease, diabetic foot ulcers, or neuropathy should use caution when starting Invokana. Patients should be counseled on preventative foot care and common signs of infection. If patients experience symptoms of infection, pain, ulcers, or sores in the lower limbs, Invokana should be stopped.

Volume Depletion

Invokana has been known to cause intravascular volume contraction which presents as hypotension or short-term changes to creatinine. Volume depletion has been shown to cause acute kidney injury (AKI) resulting in hospitalization and sometimes dialysis. Invokana should be used with caution in patients with eGFR of less than 60 mL/min/1.73 m2, elderly patients, or patients taking loop diuretics. These patients could have an elevated risk of developing hypotension and volume depletion. Providers should monitor patients for signs of volume depletion throughout treatment with Invokana.

Ketoacidosis

Invokana has been reported to cause ketoacidosis. Ketoacidosis is a severe, life-threatening event that needs immediate hospitalization and could be fatal. The risk of developing ketoacidosis is elevated with higher doses of SGLT2 inhibitors such as Invokana.

Patients with symptoms associated with metabolic acidosis should be evaluated for the possibility of ketoacidosis without regard to blood glucose levels. Ketoacidosis can still be present despite blood glucose levels less than 250 mg/dL. Symptoms include signs of dehydration and metabolic acidosis, such as vomiting, nausea, malaise, shortness of breath, and abdominal pain. If suspected, Invokana should be stopped, and the patient should be assessed and treated appropriately with insulin, carbohydrate replacement, and fluid.

A patient’s history should be evaluated prior to starting Invokana, as pancreatic insulin deficiency, caloric restriction, and alcohol abuse could predispose an individual to ketoacidosis. Patients undergoing surgery should stop Invokana 3 days prior to the surgery. If patients anticipate a clinical situation known to cause ketoacidosis, such as surgery or prolonged fasting, providers should consider stopping Invokana.

Urosepsis and Pyelonephritis

Invokana has caused cases of severe urinary tract infections involving urosepsis and pyelonephritis. Occurrences have sometimes required hospitalization. If a patient presents with signs of a urinary tract infection, they should be treated appropriately.

Hypoglycemia with Concomitant Use of Insulin Products

Invokana can cause hypoglycemia when used in combination with other products that lower blood glucose, such as insulin. Dose adjustments to insulin may be required to prevent the development of hypoglycemia. Patients should be counseled on common signs and symptoms of hypoglycemia.

Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)

Necrotizing fasciitis of the perineum, also known as Fournier’s gangrene, is a rare but potentially fatal infection that requires immediate intervention with surgery. Occurrences can result in hospitalization, surgeries, and death. Patients should be aware of the signs and symptoms associated with necrotizing fasciitis, such as pain, erythema, tenderness, or swelling of the genital or perineal area. Symptoms can also include malaise or fever.

If necrotizing fasciitis is suspected, providers may choose to treat the infection with broad-spectrum antibiotics and possibly surgical debridement. Invokana should be stopped and blood glucose levels should be monitored.

Genital Mycotic Infections

Invokana has been shown to elevate the risk of genital mycotic infections. Patients who have had genital mycotic infections in the past or who are uncircumcised males have a higher likelihood of developing genital mycotic infections. If suspected, providers should monitor and treat the patient appropriately.

Hypersensitivity Reactions

Invokana has been shown to cause severe hypersensitivity reactions, including anaphylaxis and angioedema, within hours or days of starting therapy. If anaphylaxis or angioedema should occur, Invokana should be stopped and the patient should seek medical attention.

Bone Fracture

Patients have an elevated risk of bone fracture after starting Invokana. This risk can be increased as early as 12 weeks after starting treatment. Providers should assess a patient’s risk factors for developing a fracture before starting Invokana.

Drug Interactions

UGT Enzyme Inducers

UGT inducers include drugs such as rifampin, ritonavir, phenobarbital, and phenytoin. In patients who are on a UGT inducer and have an eGFR of less than 60 mL/min/1.73 m2, increase the dose of Invokana to 200 mg daily in those already tolerating 100 mg.

Digoxin

When co-administered with digoxin, Invokana has been shown to increase digoxin concentrations. Use caution when taking concomitantly and monitor appropriately to avoid digoxin toxicity.

Positive Urine Glucose Test

SGLT2 inhibitors such as Invokana can elevate glucose excretion in the urine. This phenomenon will cause positive urine glucose tests if administered. Therefore, do not use urine glucose tests to monitor glycemic control in patients taking Invokana.

Interference with 1,5-anhydroglucitol (1,5-AG) Assay

The 1,5-AG assay is not a reliable form of glycemic control monitoring in patients taking Invokana. Other methods should be implemented to monitor glucose control in patients taking SGLT2 inhibitors.

Frequently Asked Questions