Invokana (canagliflozin)

How does Invokana work?

Invokana is a sodium-glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 is expressed in the proximal renal tubule and is responsible for most reabsorption of glucose from the tubular lumen. Invokana inhibits SGLT2, leading to decrease reabsorption of glucose and increased urinary glucose excretion.

Invokana also increases the delivery of sodium to the distal tubule by blocking SGLT2-dependent sodium reabsorption. This is believed to increase tubuloglomerular feedback and reduce intraglomerular pressure.

Dosage and How to Use

Invokana is available in the following dosage strengths:

• 100 mg tablets
• 300 mg tablets

The dosage of Invokana is determined renal function based on the estimated glomerular filtration rate (eGFR) (mL/min/1.73 m²)

eGFR 60 or greater

• 100 mg orally once daily, taken before the first meal of the day. The dose can be increased to 300 mg once daily for additional glycemic control.

eGFR 30 to less than 60

• 100 mg once daily.

eGFR less than 30

• Initiation is not recommended. However, patients with albuminuria higher than 300 mg/day may continue 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, CV death, and hospitalization for heart failure.

On dialysis

• Contraindicated

Invokana can be administered with or without food. It is recommended to take it before the first meal of the day.

Storage

 Store between 20°C to 25°C (68°F to 77°F). Temperature excursions are permitted between 15°C to 30°C (59°F to 86°F).

Overdosage

Contact the Poison Control Center or seek medical attention if an overdose occurs. The medical team should apply supportive care and potentially attempt to remove unabsorbed material from the gastrointestinal tract. Invokana is negligibly removed by hemodialysis and is not expected to be dialyzable by peritoneal dialysis.

Side Effects

The most common side effects of Invokana are:

• Vaginal and penile yeast infections
• Urgent need to urinate more often
• Urinating larger amounts
• Increased need to urinate at night

Serious side effects possible with Invokana are:

• Lower limb amputations
  • Call your doctor immediately if you have one of the following in your leg or foot:
    • new pain or tenderness
    • any sores, ulcers, or infections

• Ketoacidosis
  • Ketoacidosis with Invokana can happen regardless of blood sugar levels
  • Call your doctor immediately if you have one of the following warning signs of ketoacidosis:
    • Nausea
    • Vomiting
    • Abdominal pain
    • Tiredness
    • Trouble breathing

• Necrotizing fasciitis in the area between and around the anus and genitalia
  • Contact your doctor immediately if you are feeling very weak, tired, or uncomfortable and have one of the following warning signs:
    • Pain or tenderness around the anus or genitals
    • Swelling around the genitals
    • Redness of the skin around the anus or genitals

• Vaginal yeast infections
  • Symptoms may include vaginal odor, yellowish or white vaginal discharge, and vaginal itching.

• Penile yeast infections
  • Symptoms may include redness or itching of the penis, foul-smelling discharge of the penis, and pain in the skin around the penis.
• Serious urinary tract infections (UTIs)
  • Potential symptoms of a UTI include a burning feeling when urinating, a need to urinate more often, the need to urinate right away, pain in the lower part of the stomach, or blood in the urine.
• Hypoglycemia
  • Hypoglycemia can occur when using Invokana in combination with sulfonylurea or insulin.
• Serious allergic reactions
• Bone fractures
• Dehydration

This is not a comprehensive list of possible side effects. Please talk to your doctor or pharmacist for more information.

Warnings & Precautions

Lower Limb Amputation

• An increased risk of lower limb amputations associated with Invokana use versus placebo was observed in studies. Before starting treatment with 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. Patients need to be informed about the importance of routine preventative foot care.

Ketoacidosis

• Ketoacidosis, a condition requiring urgent hospitalization, has been reported in clinical trials and postmarket surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors. Fatal cases of ketoacidosis have been reported in patients taking Invokana. Before starting treatment with Invokana, consider factors in the patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse.

Volume depletion

• There have been post-marketing reports of acute kidney injury likely related to volume depletion, some requiring hospitalizations and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including Invokana. Patients with impaired renal function, elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension.

Urosepsis and Pyelonephritis

• There have been postmarketing reports of serious urinary tract infections (e.g., urosepsis and pyelonephritis) requiring hospitalization in patients receiving SGLT2 inhibitors, including Invokana.

Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues

• Insulin and insulin secretagogues are known to cause hypoglycemia; Invokana may increase the risk of hypoglycemia when used concomitantly. A lower dose of insulin or insulin secretagogue may be required.

Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)

• Fournier’s gangrene, a rare but serious and life-threatening necrotizing infection, has been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors, including Invokana.

Genital Mycotic Infections

• Invokana increases the risk of genital mycotic infections.

Hypersensitivity Reactions

• Hypersensitivity reactions (e.g., angioedema and anaphylaxis) have been reported in patients taking Invokana.

Bone Fracture

• Studies have shown an increased risk of bone fracture, seen as early as 12 weeks after treatment initiation, in patients taking Invokana.

Drug Interactions and Other Interactions

UGT enzyme inducers

• UGT enzyme inducers decrease Invokana exposure and may reduce efficacy.
• Examples of UGT enzyme inducers are rifampin, phenytoin, phenobarbital, and ritonavir.

Insulin and insulin secretagogues

•  Invokana may increase the risk of hypoglycemia when used concomitantly with insulin or insulin secretagogues.

Digoxin

• Invokana increases exposure to digoxin when used concomitantly.

Lithium

• SGLT2 inhibitors may decrease serum lithium concentrations when used concomitantly.

Laboratory test interference

• Positive urine glucose test
• Interference with 1,5-anhydroglucitol (1,5-AG) Assay

Contraindications

• Serious hypersensitivity reaction to Invokana or any ingredient, such as anaphylaxis or angioedema
• Patients on dialysis