Invokana (canagliflozin)
Invokana
Canagliflozin
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WHAT IS INVOKANA?

Invokana, also known as canagliflozin, is an oral antidiabetic medication. It has a few indications, including that it:

  • Improves glycemic control in adults with type 2 diabetes mellitus (T2DM) in addition to diet and exercise
  • Decreases the risk of serious cardiovascular events (e.g. death, myocardial infarction, stroke) in adults with T2DM and cardiovascular disease (CVD)
  • Decreases the risk of developing end-stage kidney disease (ESKD), serum creatinine doubling, death from cardiovascular causes, and hospitalization for heart failure in adults with T2DM and diabetic nephropathy with albuminuria over 300 mg/day

Controlling hyperglycemia prevents downstream complications such as kidney damage, loss of limbs, blindness, heart attack, stroke, or nerve problems. Cardiovascular and renal events in diabetes can also be detrimental. It is important that diabetes and related events remain controlled to lessen the chance of related complications. Invokana is not indicated for the treatment of type I diabetes.

HOW DOES INVOKANA WORK?

Invokana is a sodium-glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 is a transporter that reabsorbs filtered glucose in the proximal renal tubules. Invokana inhibits SGLT2, decreasing renal reabsorption of glucose and lessening the renal glucose threshold, which elevates the amount of glucose excreted into the urine. By preventing SGLT2-dependent reabsorption of glucose and sodium, Invokana also increases the amount of sodium getting to the distal tubule. This elevates tubuloglomerular feedback and decreases intraglomerular pressure.

SIDE EFFECTS

Common side effects include:

  • Yeast infection
  • Urination changes (e.g. increased urgency, increased frequency)
  • Urinary tract infection
  • Low blood sugar
  • Hypersensitivity reactions
  • Increased hemoglobin
  • Limb injury
  • Increased serum potassium
  • Increased thirst
  • Asthenia
  • Hypovolemia
  • Abdominal pain
  • Constipation

WARNINGS AND PRECAUTIONS

Lower Limb Amputation

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 development of hypoglycemia. Patients should be counseled on common signs and symptoms of hypoglycemia.

Necrotizing Fascilitis 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 should treat 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

Take Invokana exactly as your doctor tells you to take it. Typically, Invokana is taken once daily by mouth. It is best to take Invokana prior to your first meal of the day.

If you miss a dose of Invokana, take the dose as soon as you remember. If it is time for the next dose at the time that you remember, skip the missed dose and return to your normal dosing schedule. Do not take more than one dose of Invokana at the same time.

Invokana can be taken long term to control type II diabetes mellitus.

Invokana can be taken with or without food.

If you overdose with Invokana, you should immediately go to the emergency room or contact the Poison Control Center.

Avoid excessive alcohol intake, as this increases one’s risk of developing ketoacidosis while on Invokana.

Common side effects of Invokana include:

  • Yeast infections
  • Low blood sugar
  • Increased frequency and urgency in urination
  • Urinary tract infection
  • Allergic reaction
  • Low blood pressure

Serious side effects of Invokana include:

  • Amputations
  • Dehydration
  • Increased ketones in your blood or urine
  • Broken bones
  • Serious bacterial infections of the skin

It is important that you tell your doctor all of the medications, vitamins, and supplements that you take, especially if you take:

  • Diuretics
  • Phenytoin or phenobarbital
  • Rifampin
  • Digoxin
  • Ritonavir

Additionally, tell your doctor if you:

  • Have a history of amputation
  • Have nerve damage in your leg
  • Have a history of urinary tract infections or urination problems
  • Have heart disease
  • Have a history of diabetic sores or foot ulcers
  • Have blocked blood vessels
  • Have kidney problems
  • Have liver problems
  • Are on a low sodium diet
  • Are undergoing surgery
  • Are starting a more restrictive diet
  • Have pancreas problems
  • Drink alcohol often or excessively
  • Are pregnant or plan to become pregnant
  • Are breastfeeding or plan to breastfeed

Store Invokana at room temperature between 68°F to 77°F (20°C to 25°C). Invokana should be kept out of reach from children.