Key Points

• Some of the top warnings associated with Invokana (canagliflozin) treatment include the risk of amputation of a lower limb, dehydration and low blood pressure, genital yeast infections in men and women, serious allergic reactions and kidney problems. There are other serious side effects with Invokana that you should discuss with your doctor.
• While there are dangers, most side effects occur in small numbers of patients and many patients tolerate Invokana well. It is important to remember that untreated type 2 diabetes can lead to serious health problems including heart and kidney disease, blindness, nerve damage, and death.
• The most common side effect you are likely to encounter with Invokana is a genital yeast infection, in both women and men. Urinary tract infections and frequent urination are other common reactions.

Invokana (canagliflozin) is a prescription drug used with diet and exercise to lower blood sugar in adults with type 2 diabetes. It belongs to a class of medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors lower blood sugar by blocking a certain protein and causing the kidneys to remove sugar from the body through the urine.

Warnings related to Invokana

Amputations

Invokana (canagliflozin) carries a Boxed Warning for an increased risk of lower limb amputations. A Boxed Warning is the FDA’s most stringent warning for medicines.

Two clinical studies (CANVAS, CANVAS-R trial) in patients with type 2 diabetes and heart disease (or at risk for heart disease) showed that amputations occurred about twice as often in those patients taking Invokana as in patients treated with an inactive placebo.

• In the CANVAS study, 3.3% of patients (95 of 2886) receiving either the 100 mg or 300 mg dose of Invokana had an amputation compared to 1.5% of patients (22 of 1441) taking an inactive placebo. The total number of amputations were 162 for Invokana and 33 for the placebo group.
• Amputations of the toe and middle of the foot were the most common; however, amputations involving the leg, either below or above the knee, also occurred. Some patients had more than one amputation and some involved multiple limbs.
• The risk for amputation occurred with both 100 mg and 300 mg dose of Invokana.
• This Boxed Warning also applies to Invokamet and Invokamet XR, combination products that contain canagliflozin and metformin.

Your risk for amputation may be higher if you have heart disease or are at risk for heart disease, have had blocked or narrowed blood vessels, usually in the leg, nerve damage (neuropathy), diabetic foot ulcers (sores), or a history of prior amputation. Be sure to tell your doctor if you fall into any of these categories.

Contact your doctor right away if you develop any new pain or tenderness, sores or ulcers, or infections in your legs or feet. Your doctor can determine if you need to stop taking Invokana.

Learn about and engage in proper foot care if you have type 2 diabetes.

Dehydration, Low Blood Pressure

Invokana causes increased urination, which may put you at risk of dehydration (the loss of too much body water).

Dehydration may make you feel dizzy, lightheaded faint, or weak, especially when you stand up (orthostatic hypotension). This might also increase your risk for a fall.

If you take the 300 mg dose of Invokana, are 75 years of age or older, or take a loop diuretic (such as furosemide), you may be at greater risk of dehydration.

Discuss with your doctor how much fluid you should drink each day to help lower your risk for dehydration.

You could be at risk of dehydration if you:

• have low blood pressure
• take medicine to lower your blood pressure
• are on a low sodium diet
• have kidney problems
• are 65 years of age or older.

Low blood pressure (hypotension) may occur with Invokana treatment. This can happen when you are dehydrated, too.

Tell your doctor if:

• you have kidney problems are 65 years or older
• you have a history of low blood pressure
• you take certain medicines for blood pressure, such as diuretics (water pills), ACE inhibitors, or Angiotensin receptor blockers.

Yeast infections

Genital yeast infections are listed as a common side effect with SGLT2 inhibitors, including Invokana, and occur more frequently in women.

Symptoms of a vaginal yeast infection in women (also called vulvovaginitis or candidiasis):

• vaginal itching
• vaginal odor
• white or yellowish discharge that may be lumpy or look like cottage cheese
• vaginal burning discomfort or burning while urinating
• painful sexual intercourse.

In Invokana studies, the overall incidence of genital yeast infections in women was 10.6% (with the 100 mg dose), 11.6% (with the 300 mg dose) and 2.8% (inactive placebo). The number of women who had to stop treatment for this side effect was low: 0.7% of those receiving Invokana compared to 0% in the placebo group.

Symptoms of a yeast infection of the penis in men (balanitis or balanoposthitis):

• redness, itching, or swelling of the penis rash or sores on the penis
• foul smelling discharge from the penis
• pain in the skin around the penis
• tight, shiny skin on the head of your penis
• painful urination or not being able to urinate
• swollen glands near your groin.

Some men who are not circumcised may have swelling of the penis that makes it difficult to pull back the skin around the tip of the penis. Balanitis is most likely to occur in men who have a tight foreskin that is difficult to pull back, or who have poor hygiene. An allergy to condoms or spermicides may also worsen balanitis caused by yeast.

In men, genital yeast infections (e.g., candidal balanitis, balanoposthitis) occurred in 4.2% (with the 100 mg dose). 3.8% (with the 300 mg dose) and 0.7% (inactive placebo).

Talk to your doctor about what to do if you should get a yeast infection. This is treatable and few patients stop treatment due to this side effect. Oral prescription or over-the-counter topical antifungal treatment may be treatment options.

Ketoacidosis

Ketoacidosis is when you have increased ketones in your blood or urine, and can occur during treatment with Invokana. This is a serious condition, may need treatment in a hospital and can lead to death. Ketoacidosis can happen with Invokana even if your blood sugar is less than 250 mg/dL. You may be at greater risk of ketoacidosis if you are sick or undergoing surgery.

Stop taking Invokana and contact your doctor right away if you get any of the following symptoms:

• nausea
• tiredness
• vomiting
• trouble breathing
• stomach area (abdominal) pain.

If you get any of these symptoms during treatment with Invokana, if possible, check for ketones in your urine, even if your blood sugar is less than 250 mg/dL.

Urinary tract infections

Serious urinary tract infections (UTIs) may be a risk with Invokana treatment and other SGLT2 inhibitors. Some UTIs have resulted in hospitalization.

In clinical studies, UTIs occurred in 5.9% of patients receiving the 100 mg dose of Invokana, 4.4% of patients receiving the 300 mg dose and 3.8% of those on the inactive placebo.

Before you start treatment with Invokana, tell your doctor if you have a history of urinary tract infections or problems with urination. If you get any of the following symptoms, tell your doctor immediately:

• burning feeling when passing urine
• a need to urinate often
• the need to urinate right away pain in the lower part of your stomach (pelvis)
• blood in your urine
• a fever, back pain, nausea, or vomiting.

Sudden kidney problems

Sudden (acute) kidney injury is a possible serious side effect with Invokana. Your doctor may need to temporarily discontinue your treatment.

Contact to your doctor right away if you:

• lower the amount of food or liquid you drink for example, if you are sick or cannot eat
• you start to lose liquids from your body for example, from vomiting, diarrhea or being in the sun too long.

If you have kidney disease, your doctor may need to reduce your dose of Invokana when you first start taking Invokana. Be sure to tell your doctor if you have a history of kidney problems.

Your doctor will follow your kidney function during treatment with Invokana.

Low blood sugar (hypoglycemia)

Low blood sugar can occur if you take Invokana with another medicine that can cause low blood sugar, such as sulfonylureas (glipizide, glimepiride) or insulin. Your medication doses may need to be adjusted.

Signs and symptoms of low blood sugar may include:

• headache
• drowsiness
• weakness
• confusion
• dizziness
• irritability
• hunger
• fast heartbeat
• sweating
• shaking or feeling jittery

Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)

Fournier’s Gangrene is a rare but serious bacterial infection that causes damage to the tissue under your skin (necrotizing fasciitis) in the area between and around the anus and genitals (perineum). This can happen in both women and men. It can require hospitalization, multiple surgeries, and may lead to death.

Seek medical attention immediately if you have fever or if you are feeling very weak, tired or uncomfortable and you have these symptoms in the area between and around your anus and genitals:

• pain
• tenderness
• swelling
• redness of the skin (erythema)

Other side effects with Invokana may include:

• serious allergic reactions, which may include redness, rash, itching, hives, and angioedema (a swelling under your skin that can occur around your eyes, lips, hands, throat, tongue, feet and/or genitals). If you have any symptoms of a serious allergic reaction, stop taking Invokana and call your doctor right away or go to the nearest hospital emergency room.
• high potassium levels in your blood, which can affect your heart and may be serious
• bone fractures (broken bones)
• increase in cholesterol

Drug interactions

Invokana is also associated with some drug interactions. Some interactions can affect your dose of Invokana and you may need a dose adjustment. Be sure to tell your doctor and pharmacist about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor and pharmacist if you take:

• diuretics (water pills)
• rifampin (for tuberculosis)
• phenytoin or phenobarbital (for seizures)
• ritonavir (for HIV infection)
• digoxin (for heart problems).

Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant while taking Invokana. Invokana may harm your unborn baby.

Invokana may also pass into your breast milk. Do not breastfeed while taking Invokana.

Talk with your doctor about the best way to control your blood sugar while you are pregnant. Also discuss the best way to feed your baby if you are taking Invokana.

Do not take Invokana:

• if you have a serious allergy to canagliflozin or any ingredient in Invokana
• if you have severe kidney impairment or are on dialysis
• if you have type 1 diabetes
• if you have severe liver disease
• to treat ketoacidosis
• if you are breastfeeding

Speak to your doctor if you think you fall into these categories.

Bottom Line

• There are many important warnings and side effects to consider before you start treatment with Invokana. Some of the top concerns include amputations, dehydration, low blood pressure, and genital yeast infections.
• Your pharmacist will give you a Medication Guide when you fill your prescription for Invokana. You should re-read it with each new refill in case of new or updated information.
• Always talk to your doctor before you start treatment with any medication about warnings, side effects and drug interactions that could affect your health.

This is not all the information you need to know about Invokana (canagliflozin) for safe and effective use. Review the full Invokana information here, and speak to your health care provider if you have questions or concerns.