INVOKAMET^® or INVOKAMET^® XR can cause serious side effects, including:

• Lactic acidosis. Metformin, one of the medicines in INVOKAMET^® or INVOKAMET^® XR, can cause a rare but serious condition called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital. Stop taking INVOKAMET^® or INVOKAMET^® XR and call your doctor right away if you have any of the following symptoms of lactic acidosis: feel cold in your hands or feet; feel very weak or tired; have unusual (not normal) muscle pain; have trouble breathing; have unusual sleepiness or sleep longer than usual; have stomach pains, nausea, or vomiting; feel dizzy or lightheaded; or have a slow/irregular heartbeat

• Diabetic ketoacidosis (increased ketones in your blood or urine) in people with type 1 diabetes mellitus and other ketoacidosis. INVOKAMET^® or INVOKAMET^® XR can cause ketoacidosis that can be life-threatening and may lead to death. Ketoacidosis is a serious condition which needs to be treated in a hospital. People with type 1 diabetes have a high risk of getting ketoacidosis. People with type 2 diabetes or pancreas problems also have an increased risk of getting ketoacidosis. Ketoacidosis can also happen in people who: are sick, cannot eat or drink as usual, skip meals, are on a diet high in fat and low in carbohydrates (ketogenic diet), take less than the usual amount of insulin or miss insulin doses, drink too much alcohol, have a loss of too much fluid from the body (volume depletion), or who have surgery. Ketoacidosis can happen even if your blood sugar is less than 250 mg/dL. Your healthcare provider may ask you to periodically check ketones in your urine or blood.
• Stop taking INVOKAMET^® or INVOKAMET^® XR and call your healthcare provider or get medical help right away if you get any of the following. If possible, check for ketones in your urine or blood, even if your blood sugar is less than 250 mg/dL:

• Amputations. INVOKAMET^® or INVOKAMET^® XR may increase your risk of lower-limb amputations. Amputations mainly involve removal of the toe or part of the foot; however, amputations involving the leg, below and above the knee, have also occurred. Some people had more than one amputation, some on both sides of the body. You may be at a higher risk of lower-limb amputation if you: have a history of amputation, have heart disease or are at risk for heart disease, have had blocked or narrowed blood vessels (usually in leg), have damage to the nerves (neuropathy) in the leg, or have had diabetic foot ulcers or sores. Call your doctor right away if you have new pain or tenderness, any sores, ulcers, or infections in your leg or foot. Your doctor may decide to stop your INVOKAMET^® or INVOKAMET^® XR for a while if you have any of these signs or symptoms. Talk to your doctor about proper foot care
• Dehydration. INVOKAMET^® or INVOKAMET^® XR can cause some people to become dehydrated (the loss of too much body water), which may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). There have been reports of sudden worsening of kidney function in people with type 2 diabetes who are taking canagliflozin, one of the medicines in INVOKAMET^® or INVOKAMET^® XR. You may be at higher risk if you take medicines to lower blood pressure, are on a low sodium (salt) diet, have kidney problems, or are 65 years of age or older. Talk to your doctor about ways to prevent dehydration including how much fluid you should drink on a daily basis. Call your healthcare provider right away if you reduce the amount of food or liquid you drink, for example if you cannot eat or you start to lose liquids from your body, for example from vomiting, diarrhea, or being in the sun too long
• Vaginal yeast infection. Symptoms of a vaginal yeast infection include: vaginal odor, white or yellowish discharge, or vaginal itching
• Yeast infection of the skin around the penis (balanitis or balanoposthitis). Swelling of an uncircumcised penis may develop that makes it difficult to pull back the skin around the tip of the penis. Other symptoms include: redness, itching, or swelling of the penis; rash; foul smelling discharge; or pain in the skin around penis

Talk to your doctor about what to do if you get symptoms of a yeast infection of the vagina or penis.

Do not take INVOKAMET^® or INVOKAMET^® XR if you:

• have severe kidney problems, have a condition called metabolic acidosis, or are allergic to canagliflozin, metformin, or any of the ingredients in INVOKAMET^® or INVOKAMET^® XR. Symptoms of an allergic reaction may include: rash; raised red patches on your skin (hives); swelling of the face, lips, mouth, tongue, and throat that may cause difficulty in breathing or swallowing

Before taking INVOKAMET^® or INVOKAMET^® XR, tell your doctor about all of your medical conditions, including if you: have type 1 diabetes or have had diabetic ketoacidosis; have a serious infection; have a history of infection of the vagina or penis; have a history of amputation; have had blocked or narrowed blood vessels, usually in your leg; have damage to the nerves (neuropathy) in your leg; have had diabetic foot ulcers or sores; have moderate to severe kidney problems; have liver problems; have a history of urinary tract infections or problems with urination; are on a low sodium (salt) diet; have ever had an allergic reaction to INVOKAMET^® or INVOKAMET^® XR; are going to get an injection of dye or contrast agents for an x-ray procedure; have heart problems, including congestive heart failure; are going to have surgery (your doctor may stop your INVOKAMET^® or INVOKAMET^® XR before you have surgery; talk to your doctor if you are having surgery about when to stop taking and when to start it again); are eating less or there is a change in your diet; are dehydrated; have a decrease in your insulin dose; have or have had problems with your pancreas, including pancreatitis or surgery on your pancreas; drink alcohol very often or drink a lot of alcohol in the short-term; have low levels of vitamin B₁₂ or calcium in your blood.

Tell your doctor if you are or plan to become pregnant, are breastfeeding, or plan to breastfeed. INVOKAMET^® or INVOKAMET^® XR may harm your unborn baby. If you become pregnant while taking INVOKAMET^® or INVOKAMET^® XR, tell your doctor as soon as possible. Talk with your doctor about the best way to control your blood sugar while you are pregnant.

If you are premenopausal (before the “change of life”), and do not have periods regularly or at all, INVOKAMET^® or INVOKAMET^® XR may increase your chance of becoming pregnant. Talk to your doctor about birth control choices while taking INVOKAMET^® or INVOKAMET^® XR, if you are not planning to become pregnant. Tell your doctor right away if you become pregnant while taking INVOKAMET^® or INVOKAMET^® XR.

INVOKAMET^® or INVOKAMET^® XR may pass into your breast milk and may harm your baby. Talk with your doctor about the best way to feed your baby if you are taking INVOKAMET^® or INVOKAMET^® XR. Do not breastfeed while taking INVOKAMET^® or INVOKAMET^® XR.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. INVOKAMET^® or INVOKAMET^® XR may affect the way other medicines work and other medicines may affect how INVOKAMET^® or INVOKAMET^® XR works.

Possible Side Effects of INVOKAMET^® or INVOKAMET^® XR

INVOKAMET^® or INVOKAMET^® XR may cause serious side effects, including:

• Serious urinary tract infections. May lead to hospitalization and have happened in people taking canagliflozin, one of the medicines in INVOKAMET^® or INVOKAMET^® XR. Tell your doctor if you have signs or symptoms of a urinary tract infection such as: burning feeling while urinating, need to urinate often or right away, pain in the lower part of your stomach (pelvis), or blood in the urine. Some people may also have a fever, back pain, nausea, or vomiting
• Low blood sugar (hypoglycemia). If you take INVOKAMET^® or INVOKAMET^® XR with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered while taking INVOKAMET^® or INVOKAMET^® XR. Signs and symptoms of low blood sugar may include: headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, sweating, shaking, or feeling jittery
• A rare but serious bacterial infection that causes damage to the tissue under the skin (necrotizing fasciitis) in the area between and around the anus and genitals (perineum). Necrotizing fasciitis of the perineum has happened in people who take canagliflozin. Necrotizing fasciitis of the perineum may lead to hospitalization, may require multiple surgeries to remove affected tissues, and may lead to death. Seek medical attention immediately if you have a fever or you are feeling very weak, tired, or uncomfortable (malaise) and you develop any of the following symptoms in the area between and around your anus and genitals: pain or tenderness, swelling, or redness of the skin (erythema)
• Serious allergic reaction. If you have any symptoms of a serious allergic reaction, stop taking INVOKAMET^® or INVOKAMET^® XR and call your doctor right away or go to the nearest hospital emergency room
• Broken bones (fractures). Bone fractures have been seen in patients taking canagliflozin. Talk to your doctor about factors that may increase your risk of bone fracture
• Low vitamin B₁₂ (vitamin B₁₂ deficiency). Using metformin for long periods of time may cause a decrease in the amount of vitamin B₁₂ in your blood. Your doctor may order blood tests to check your levels

Other common side effects of INVOKAMET^® or INVOKAMET^® XR include: nausea and vomiting; diarrhea; weakness; gas; upset stomach; indigestion; headache; changes in urination, including urgent need to urinate more often, in larger amounts, or at night.

These are not all the possible side effects of INVOKAMET^® or INVOKAMET^® XR.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to Janssen Scientific Affairs, LLC at 1-800-526-7736.

Please read full Product Information, including Boxed Warning, and Medication Guide for INVOKAMET^® and INVOKAMET^® XR.

Canagliflozin is licensed from Mitsubishi Tanabe Pharma Corporation.

Trademarks are those of their respective owners.

cp-06259v11