Invokana: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on Aug 28, 2023.

1. How it works

• Invokana is a brand (trade) name for canagliflozin which may be used in the treatment of type 2 diabetes.
• Canagliflozin works by blocking the sodium-glucose co-transporter 2 (SGLT2) which is a protein located in the early proximal tubule of a nephron (a kidney cell), which is responsible for the reabsorption of glucose from the blood that flows through the kidneys (the glomerular filtrate) back into circulation. By blocking this transporter, canagliflozin prevents glucose from being reabsorbed and increases how much glucose is excreted in the urine. This helps to lower blood sugar and improve A1C.
• Invokana belongs to the class of medicines called SGLT-2 inhibitors.

2. Upsides

• Invokana may be used in the treatment of type 2 diabetes alongside diet modification and increased exercise.
• Invokana may also be given to reduce the risk of future cardiovascular events, such as a heart attack or stroke, in people with type 2 diabetes who also have heart disease.
• Invokana reduces the risk of worsening or end-stage kidney disease, cardiovascular death, and being admitted into hospital with heart failure in adults with type 2 diabetes or diabetic kidney disease.
• Invokana is effective at reducing blood glucose levels, and HbA1c, and it also reduces body weight.
• Invokana may be given in addition to other medications for diabetes, such as insulin, metformin, or sulfonylureas.
• Most people taking Invokana lose around 2 to 3 kg of weight. However, some may gain weight.
• Invokana is taken orally.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Common side effects of Invokana include low blood sugar levels, bladder pain, genital infections, a change in urination or pain when urinating, constipation, nausea, shortness of breath, and tiredness.
• Invokana use has been associated with an approximate doubling of the risk of lower-limb amputations in people with type 2 diabetes with cardiovascular disease or at risk of cardiovascular disease. Amputations of the toe and midfoot were the most common, although some people had their leg amputated and others required multiple amputations. Patients should be assessed for risk factors that increase the likelihood of amputations and monitored for circulatory problems in the lower limbs during treatment.
• An increased risk of bone fracture has also been observed in patients taking Invokana for more than twelve weeks.
• Invokana is not suitable for people with type 1 diabetes or to treat diabetic ketoacidosis.
• Invokana causes an increase in urination which can lead to dehydration or a drop in blood pressure. Any dehydration or volume depletion should be corrected before starting Invokana. Those with volume depletion, seniors with kidney disease, or those who are also taking diuretics, are more at risk.
• Invokana is not suitable for people with moderate-to-severe kidney disease with an eGFR of less than 30 mL/min/1.73m2. Lower dosages (100mg/daily) should be given to people with an eGFR of 30-60 mL/min/1.73m2. If Invokana is started and then a patient's eGFR drops to less than 30 mL/min/1.73m2 then Invokana should be discontinued. People more at risk of acute kidney injury with Invokana include those who are dehydrated, taking certain medications, such as NSAIDs, ACE inhibitors, ARBs, or diuretics, or those with reduced calorie intake.
• Invokana has been associated with an increased risk of diabetic ketoacidosis (caused by a severe lack of insulin), which may be life-threatening. This may be associated with severe metabolic acidosis. If this occurs, prompt treatment for ketoacidosis should be initiated and Invokana discontinued. Those with pancreatic insulin deficiency, on a calorie-restricted diet, or with an excessive alcohol intake are more at risk.
• Treatment with Invokana increases the risk of urinary tract infections, genital fungal infections, and a rare necrotizing infection called necrotizing fasciitis of the perineum (Fournier's gangrene), which causes pain, tenderness, redness, and swelling in the genital area.
• LDL cholesterol levels may increase with Invokana treatment.
• Invokana is not recommended during the second and third trimester of pregnancy and there is a lack of data assessing the risk for the first trimester of pregnancy. However, the risk of Invokana use in the first trimester should be weighed up against the risk of uncontrolled diabetes on the fetus with regard to birth defects and miscarriage.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Invokana is effective at lowering blood glucose levels in people with type 2 diabetes. It also reduces the risk of future cardiovascular events (such as a heart attack or stroke) and kidney disease but is associated with an increased risk of lower limb amputations and is not suitable for people with moderate-to-severe kidney disease.

5. Tips

• Tell your doctor if you develop any signs of infection, pain, or tenderness, sores, or ulcers involving the legs or feet.
• Invokana is usually taken once daily, before the first meal of the day. Your doctor will start you on 100mg and may increase the dose to 300mg if you need additional blood sugar control, are tolerating Invokana well, and do not have kidney disease.
• Tell your doctor before you start Invokana if you have a history of amputation, heart disease, poor circulation or nerve damage, liver problems, urinary problems, are planning to have surgery, or are on a low-sodium diet.
• Take Invokana exactly as prescribed. If you miss a dose, take it as soon as you remember but not if it is within eight hours of your next dose, just go back to your regular dosing schedule.
• Invokana should be taken in addition to any other medications prescribed by your doctor. You should also adhere to any dietary recommendations and undertake regular physical activity. See your doctor if you develop any kind of infection, are scheduled for surgery, or are dealing with a lot of stress as your medication requirements may change.
• Invokana may cause your blood pressure to drop. This is more likely when you first start taking Invokana, in seniors, in people already with low blood pressure, in those taking a low sodium diet, and in those taking diuretics. This may make you feel dizzy or faint. Talk to your doctor if this happens.
• Tell your doctor immediately if you develop signs or symptoms of diabetic ketoacidosis which may include excessive thirst, frequent urination, abdominal pain, fruity breath, or severe metabolic acidosis which may include nausea and vomiting, shortness of breath, or fatigue. Educate your friends and family about the signs of diabetic ketoacidosis and metabolic acidosis to watch out for.
• Invokana has been associated with an increased risk of urinary tract infections. If you develop symptoms such as burning or pain when urinating, an increased frequency of urination, fever, or back or pelvic pain, see your doctor.
• Invokana may also increase your risk of genital infections. Symptoms of a vaginal yeast infection include a white or yellowish vaginal discharge, vaginal itching, or vaginal odor. Symptoms of a yeast infection of the penis include redness, itching, or swelling of the penis, a foul-smelling discharge, and penile pain.
• If you are intending to become pregnant while taking Invokana, talk to your doctor before you conceive.

6. Response and effectiveness

• Blood sugar levels started to decline soon after the first dose of Invokana. Higher dosages correspond to a greater drop in blood sugar levels. It takes 4 to 5 days of regular once-daily dosing with Invokana for blood levels to drop to a consistent level, known as steady-state.
• Within 26 weeks, HbA1C levels of less than 7% were seen by 45% of patients taking Invokana 100mg and by 62% of patients taking Invokana 300mg.
• For the beneficial effects to be seen with regards to a reduction in the risk of cardiovascular or kidney disease, Invokana needs to be taken long-term.
• After 26 weeks, patients lost on average 2.2 kg with Invokana 100mg and 3.9kg with Invokana 300mg

7. Interactions

Medicines that interact with Invokana may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Invokana. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Invokana include:

• acetazolamide
• anticonvulsants such as phenytoin or phenobarbital
• antipsychotics, such as aripiprazole or clozapine
• beta-blockers, such as atenolol, labetalol, and metoprolol, may enhance the hypoglycemic effects
• ciprofloxacin or gatifloxacin
• corticosteroids, such as prednisone or cortisone
• digoxin
• diuretics, such as bumetanide, HCTZ, and bendroflumethiazide, which may enhance the potential for volume depletion
• HIV medications, such as amprenavir, atazanavir, fosamprenavir, and ritonavir
• hormones, such as ethinylestradiol and hydroxyprogesterone
• insulin (may increase the risk of hypoglycemia)
• isoniazid
• rifampin
• other medications that affect blood sugar levels or are used for diabetes, such as glimepiride, or metformin.

Invokana may also enhance the toxic effects of alcohol, causing flushing. Alcohol may also increase the risk of hypoglycemia and diabetic ketoacidosis.

Urine glucose tests should not be used to monitor glucose control in people receiving SGLT2 inhibitors such as Invokana as these increase urinary glucose excretion and will lead to positive urine glucose tests. Alternative methods to monitor glucose control should be used. Interference with 1,5-AG assays may also occur.

Note that this list is not all-inclusive and includes only common medications that may interact with Invokana. You should refer to the prescribing information for Invokana for a complete list of interactions.

References

• Invokana (canagliflozin). Updated 04/2023. Cardinal Health https://www.drugs.com/pro/invokana.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Invokana only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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