VOKANAMET 150 mg/850 mg FILM-COATED TABLETS

2. What you need to know before you take Vokanamet

Do not take Vokanamet

• if you are allergic to canagliflozin, metformin, or any of the other ingredients of this medicine (listed in section 6)
• if you have liver problems
• if you have severe kidney problems
• if you have uncontrolled diabetes with, for example, severe hyperglycemia (high blood sugar), nausea, vomiting, diarrhea, rapid weight loss, lactic acidosis (see "Risk of lactic acidosis" below), or ketoacidosis. Ketoacidosis is a condition in which substances called "ketone bodies" accumulate in the blood, which can lead to a pre-diabetic coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or if your breath develops an unusual fruity odor
• if you have any severe infection
• if you have lost a lot of fluid from your body (dehydration), e.g., due to severe or prolonged diarrhea or if you have vomited several times in a row
• if you have a pre-diabetic coma
• if you have recently had a heart attack or have severe blood circulation problems, such as "shock" or breathing difficulties
• if you drink excessive amounts of alcohol (either every day or from time to time)
• if you have or have recently had heart failure.

Warnings and precautions

Risk of lactic acidosis

Vokanamet may cause a very rare but very serious side effect called lactic acidosis, especially if your kidneys are not working properly. The risk of developing lactic acidosis is also increased with uncontrolled diabetes, severe infections, prolonged fasting, or alcohol consumption, dehydration (see more information below), liver problems, and any medical condition in which a part of the body has a reduced oxygen supply (such as acute and severe heart disease).

If any of the above applies to you, consult your doctor for further instructions.

Stop taking Vokanamet temporarily if you have a condition that may be associated with dehydration(significant loss of body fluids), such as severe vomiting, diarrhea, fever, heat exposure, or if you drink less fluid than usual. Consult your doctor for further instructions.

Stop taking Vokanamet and talk to a doctor or go to the nearest hospital immediately if you experience any of the symptoms that lactic acidosis produces,as this condition can lead to a coma.

The symptoms of lactic acidosis include:

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• general feeling of discomfort, with intense tiredness
• difficulty breathing
• reduction of body temperature and heart rate

Lactic acidosis is a medical emergency and should be treated in a hospital.

Consult your doctor, pharmacist, or nurse before starting to take Vokanamet and during treatment:

• to know what you can do to prevent dehydration (see section 4 for symptoms of dehydration)
• if you have type 1 diabetes because Vokanamet should not be used to treat this disease
• if you experience rapid weight loss, feeling sick or being sick, stomach pain, excessive thirst, rapid and deep breathing, confusion, drowsiness, or unusual tiredness, sweet smell on your breath, sweet or metallic taste in your mouth, or different smell of your urine or sweat, talk to your doctor or go to the nearest hospital immediately. These symptoms may be signs of a "diabetic ketoacidosis" - a rare but serious, sometimes potentially fatal problem that you may have with diabetes due to increased levels of "ketone bodies" in your urine or blood, detected in analyzes. The risk of developing "diabetic ketoacidosis" may be increased with prolonged fasting, excessive alcohol consumption, dehydration, sudden reduction in insulin dose, or increased need for insulin due to major surgery or serious illness
• if you are going to undergo major surgery or a procedure that requires prolonged fasting, ask your doctor if you should stop taking Vokanamet and when you should start taking it again.
• if you have ever had severe heart disease or if you have had a stroke
• if you are taking medicines to lower your blood pressure (antihypertensives) or if you have ever had low blood pressure (hypotension). You can find more information in the section "Other medicines and Vokanamet"
• if you have had a lower limb amputation
• It is essential that you regularly check your feet and follow any other advice about foot care, in addition to proper hydration, that your doctor has indicated. You should immediately inform your doctor if you notice any wound or discoloration or if you experience any sensitivity or pain in your feet. Some studies indicate that taking canagliflozin may have contributed to the risk of lower limb amputation (mainly amputations of the toes and midfoot)
• Consult your doctor immediately if you present a combination of symptoms of pain, pain on palpation, redness, or inflammation of the genitals or the area between the genitals and the anus, with fever or general malaise. These symptoms could be a sign of a rare but serious, sometimes potentially fatal infection called necrotizing fasciitis of the perineum or Fournier's gangrene, which destroys tissue under the skin. Fournier's gangrene should be treated immediately.
• if you have symptoms of a fungal genital infection such as irritation, itching, unusual discharge, or odor.
• if you have a severe kidney or urinary tract infection with fever. Your doctor may ask you to stop taking Vokanamet until you have recovered.

Kidney function

You will have a kidney check through a blood test before starting to take Vokanamet. During treatment with Vokanamet, your doctor will check your kidney function at least once a year or more frequently if you are an elderly person and/or if your kidney function is worsening.

Surgery

If you need to undergo major surgery, you should stop taking Vokanamet during the procedure and for a period after it. Your doctor will decide when you should stop taking Vokanamet and when you should start taking it again.

Your doctor will decide if you need any other treatment to control your blood sugar while you stop taking Vokanamet. It is essential that you follow your doctor's instructions exactly.

Glucose in urine

Due to the way canagliflozin works, your urine will test positive for sugar (glucose) while you are taking this medicine.

Children and adolescents

Vokanamet is not recommended for children and adolescents under 18 years of age, as there is no data available for these patients.

Other medicines and Vokanamet

If you need to be given an injection of a contrast medium that contains iodine into your bloodstream, for example, in the context of an X-ray or scan, you should stop taking Vokanamet before the injection or at the time of the injection. Your doctor will decide when you should stop taking Vokanamet and when you should start taking it again.

Tell your doctor if you are taking, have recently taken, or might take any other medicines. You may need more frequent blood glucose and kidney function tests, or your doctor may need to adjust the dose of Vokanamet. It is especially important to mention the following:

• insulin or a sulfonylurea (such as glimepiride or glipizide) for diabetes - your doctor may decide to reduce the dose to avoid excessive lowering of blood sugar levels (hypoglycemia)
• medicines that increase urine production (diuretics)
• St. John's Wort or hypericum (a herbal medicine used to treat depression)
• carbamazepine, phenytoin, or phenobarbital (medicines used to control seizures)

• lithium (a medicine used to treat bipolar disorder)

• efavirenz or ritonavir (medicines used to treat HIV infection)
• rifampicin (an antibiotic used to treat tuberculosis)
• cholestyramine (a medicine used to lower blood cholesterol levels). See section 3, "How to take this medicine"
• digoxin or digitoxin (medicines used for certain heart problems). If you take Vokanamet, you may need to have your digoxin or digitoxin blood levels measured
• dabigatran (an anticoagulant medicine that reduces the risk of blood clots)
• medicines that contain alcohol. See section "Vokanamet with alcohol"
• cimetidine (a medicine used to treat stomach problems)
• corticosteroids (used to treat a range of disorders, such as severe skin inflammation or asthma) given by mouth, injection, or inhalation
• beta-2 agonists (such as salbutamol or terbutaline) used to treat asthma
• medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• certain medicines used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).

Taking Vokanamet with alcohol

Avoid excessive alcohol consumption while taking Vokanamet, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking or continuing to take this medicine.

Canagliflozin, one of the components of Vokanamet, should not be used during pregnancy. Ask your doctor about the best way to control your blood sugar without Vokanamet as soon as you know you are pregnant.

You should not take this medicine if you are breastfeeding. Ask your doctor if you should stop taking this medicine or if you should stop breastfeeding.

Driving and using machines

Vokanamet has no or negligible influence on the ability to drive, ride a bicycle, or use tools or machines. However, dizziness or drowsiness has been reported, which may affect your ability to drive, ride a bicycle, or use tools or machines.

Taking Vokanamet with other diabetes medicines called sulfonylureas (such as glimepiride or glipizide) or insulin may increase the risk of low blood sugar (hypoglycemia). Symptoms include blurred vision, tingling in the lips, tremors, sweating, pallor, mood change, anxiety, or confusion. All of this may affect your ability to drive, ride a bicycle, or use tools or machines. Tell your doctor as soon as possible if you have any symptoms of low blood sugar.

Vokanamet contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet; this is essentially "sodium-free".

3. How to take Vokanamet

Follow exactly the instructions of administration of this medicine given to you by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

How much to take

• The dose of Vokanamet is one tablet twice a day.
• The concentration of Vokanamet that you should take will vary depending on your condition and the amount of canagliflozin and metformin needed to control your blood sugar.
• Your doctor will prescribe the correct dose for you.

How to take this medicine

• Swallow the tablet whole with water.
• It is best to take the tablet with a meal. This will reduce the likelihood of stomach upset.
• Try to take it at the same time every day. This will help you remember to take it.
• If your doctor has prescribed this medicine with a cholesterol-lowering medicine such as cholestyramine, you should take this medicine at least 1 hour before or 4 to 6 hours after taking the cholesterol-lowering medicine.

Your doctor may prescribe Vokanamet with another medicine to lower your blood sugar. Remember to take all your medicines as directed by your doctor to get the best results for your health.

Diet and exercise

To help control your diabetes, you should also follow the advice of your doctor, pharmacist, or nurse about diet and exercise. In particular, if you are following a weight-control diabetic diet, you should continue it while taking this medicine.

If you take more Vokanamet than you should

Since Vokanamet contains metformin, if you take more medicine than you should, you may develop lactic acidosis. If this happens to you, you may need immediate treatment in a hospital, as lactic acidosis can cause a coma. The symptoms of lactic acidosis include vomiting, stomach pain, muscle cramps, general feeling of discomfort with intense tiredness, or difficulty breathing. Other symptoms are a reduction in body temperature and heart rate. Stop taking this medicine immediately and contact a doctor or the nearest hospital (see section 2). Bring the medicine pack with you.

If you forget to take Vokanamet

• If you forget to take a dose, take it as soon as you remember. However, if it is already time for the next dose, skip the missed dose.
• Do not take a double dose to make up for the missed dose.

If you stop taking Vokanamet

Your blood sugar levels may rise if you stop taking this medicine. Do not stop taking this medicine without talking to your doctor first.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Stop taking Vokanamet and talk to a doctor or go to the nearest hospital immediately if you notice any of the following serious adverse effects:

Severe allergic reaction (rare, may affect up to 1 in 1,000 people)

Possible symptoms of a severe allergic reaction may include:

• swelling of the face, lips, mouth, tongue, or throat that can cause difficulty breathing or swallowing.

Lactic acidosis (very rare, may affect up to 1 in 10,000 people)

Vokanamet may cause a very rare (may affect up to 1 user in 10,000), but very serious, adverse effect called lactic acidosis (see section "Warnings and precautions"). If this happens to you, you must stop taking Vokanamet and talk to a doctor or go to the nearest hospital immediately, as lactic acidosis can lead to coma.

Diabetic ketoacidosis (rare, may affect up to 1 in 1,000 people)

These are symptoms of diabetic ketoacidosis (see also section 2):

• increase in "ketone bodies" in your urine or blood
• rapid weight loss
• nausea or vomiting
• stomach pain
• excessive thirst
• rapid and deep breathing
• confusion
• unusual drowsiness or fatigue
• sweet smell in your breath, sweet taste or metallic taste in your mouth, or different smell of your urine or sweat.

This can occur regardless of blood glucose levels. Your doctor may decide to interrupt treatment with Vokanamet temporarily or permanently.

Dehydration (uncommon, may affect up to 1 in 100 people)

• excessive loss of fluids from your body (dehydration). This effect is more frequently observed in elderly people (75 years or older), people with kidney problems, and people taking diuretics

Possible symptoms of dehydration are:

• feeling of dizziness or lightheadedness
• loss of consciousness (fainting) or feeling of dizziness or fainting when standing up
• very dry or sticky mouth, intense feeling of thirst
• feeling of great tiredness or weakness
• little or no urination
• rapid heartbeat.

Report to your doctor as soon as possible if you experience any of the following adverse effects:

Hypoglycemia (very common, may affect more than 1 in 10 people)

• low blood sugar (hypoglycemia) - when taking this medicine with insulin or with a sulfonylurea (such as glimepiride or glipizide)

Possible symptoms of low blood sugar are:

• blurred vision
• tingling in the lips
• tremors, sweating, paleness
• change in mood or feeling of anxiety or confusion.

Your doctor will explain how to treat low blood sugar and what to do if you have any of the above symptoms.

Urinary tract infections (common, may affect up to 1 in 10 people)

• These are signs of a serious urinary tract infection, e.g.,
• • fever and/or chills
  • burning sensation when passing fluid (urinating)
  • back or side pain.

Although rare, if you notice blood in your urine, inform your doctor immediately.

Other adverse effects of treatment with canagliflozin alone:

Very common (may affect more than 1 in 10 people)

• vaginal fungal infection.

Common (may affect up to 1 in 10 people)

• skin rash or redness of the penis or foreskin (fungal infection)
• changes in urine (including more frequent need to urinate or increased urine production, urgent need to urinate, need to urinate at night)
• constipation
• feeling of thirst
• feeling sick (nausea)
• blood tests may indicate changes in lipid levels (cholesterol) and increased red blood cell count in your blood (hematocrit).

Uncommon (may affect up to 1 in 100 people)

• skin rash or redness - this can cause itching and include raised bumps, rash with discharge, or blisters
• hives
• blood tests may show changes related to kidney function (increased creatinine or urea) or increased potassium
• blood tests may show increased phosphate levels in your blood
• bone fracture
• kidney failure (mainly as a result of significant loss of fluid from your body)
• amputations of lower limbs (mainly toes) especially if you have a high risk of heart disease
• phimosis - difficulty retracting the foreskin from the tip of the penis.
• skin reactions after exposure to sunlight.

Frequency not known (cannot be estimated from available data)

• necrotizing fasciitis of the perineum or Fournier's gangrene, a serious infection of the soft tissues of the genitals or the area between the genitals and the anus.

Adverse effects during treatment with metformin alone that were not described for canagliflozin:

• very common: feeling sick (nausea), being sick (vomiting), diarrhea, stomach pain, and loss of appetite

• common: metallic taste (altered taste), decreased vitamin B12 levels (can cause anemia - low red blood cell count)

• very rare: changes in liver function tests, hepatitis (a liver problem), and itching.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Vokanamet

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the bottle and the box after EXP. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Do not use Vokanamet if you notice visible signs of deterioration or tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Vokanamet

• The active ingredients are canagliflozin and metformin hydrochloride.

• Each 50 mg/850 mg tablet contains canagliflozin hemihydrate, equivalent to 50 mg of canagliflozin and 850 mg of metformin hydrochloride.
• Each 50 mg/1,000 mg tablet contains canagliflozin hemihydrate, equivalent to 50 mg of canagliflozin and 1,000 mg of metformin hydrochloride.
• Each 150 mg/850 mg tablet contains canagliflozin hemihydrate, equivalent to 150 mg of canagliflozin and 850 mg of metformin hydrochloride.
• Each 150 mg/1,000 mg tablet contains canagliflozin hemihydrate, equivalent to 150 mg of canagliflozin and 1,000 mg of metformin hydrochloride.

• Tablet core: microcrystalline cellulose, hypromellose, sodium croscarmellose, and magnesium stearate.
• Coating:
• 50 mg/850 mg tablets: macrogol 3350, polyvinyl alcohol, talc, titanium dioxide (E171), red iron oxide (E172), and black iron oxide (E172).

• 50 mg/1,000 mg tablets: macrogol 3350, polyvinyl alcohol, talc, titanium dioxide (E171), yellow iron oxide (E172), and red iron oxide (E172).
• 150 mg/850 mg tablets: macrogol 3350, polyvinyl alcohol, talc, titanium dioxide (E171), and yellow iron oxide (E172).
• 150 mg/1,000 mg tablets: macrogol 3350, polyvinyl alcohol, talc, titanium dioxide (E171), red iron oxide (E172), and black iron oxide (E172).

Appearance of Vokanamet and Package Contents

• Vokanamet 50 mg/850 mg film-coated tablets (tablets) are pink, capsule-shaped, 20 mm long, with "CM" engraved on one side and "358" on the other side.
• Vokanamet 50 mg/1,000 mg film-coated tablets (tablets) are beige, capsule-shaped, 21 mm long, with "CM" engraved on one side and "551" on the other side.
• Vokanamet 150 mg/850 mg film-coated tablets (tablets) are pale yellow, capsule-shaped, 21 mm long, with "CM" engraved on one side and "418" on the other side.
• Vokanamet 150 mg/1,000 mg film-coated tablets (tablets) are purple, capsule-shaped, 22 mm long, with "CM" engraved on one side and "611" on the other side.

Vokanamet is available in HDPE bottles with child-resistant closures. The package sizes are boxes of 20 and 60 tablets, and multiple packages of 180 tablets (3 bottles containing 60 tablets each).

Not all package sizes may be marketed.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen-Cilag SpA

Via C. Janssen

Borgo San Michele

04100 Latina

Italy

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet: September 2024.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).