Vokanamet 50 mg/1000 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Vokanamet 50 mg/850 mg film-coated tablets

Vokanamet 50 mg/1,000 mg film-coated tablets

Vokanamet 150 mg/850 mg film-coated tablets

Vokanamet 150 mg/1,000 mg film-coated tablets

canagliflozin/metformin hydrochloride

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are possible adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Vokanamet is and what it is used for

2. What you need to know before taking Vokanamet

3. How to take Vokanamet

4. Possible side effects

5. How to store Vokanamet

6. Contents of the pack and other information

1. What Vokanamet is and what it is used for

Vokanamet contains two different active substances, canagliflozin and metformin. These are two medicines that work together through different mechanisms to lower blood glucose (sugar) levels and may help prevent heart disease in adults with type 2 diabetes.

This medicine is given alone or in combination with other medicines you may already be taking to treat your type 2 diabetes (such as insulin, a DPP-4 inhibitor [such as sitagliptin, saxagliptin or linagliptin], a sulfonylurea [such as glimepiride or glipizide], or pioglitazone) that lower blood sugar levels. You may already be taking one or more of these medicines to treat your type 2 diabetes. Vokanamet is used when your blood sugar levels cannot be adequately controlled with metformin alone or in combination with other antidiabetic medicines. If you are already taking canagliflozin and metformin as separate tablets, Vokanamet may replace them in a single tablet.

It is important that you continue to follow your doctor’s or nurse’s advice regarding diet and exercise.

What is type 2 diabetes?

Type 2 diabetes is a condition in which the body does not produce enough insulin and/or the insulin produced does not work as well as it should. It may also be that your body produces too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical conditions, such as heart disease, kidney disease, blindness, and amputations.

2. What you need to know before taking 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 reduction in kidney function
• if you have uncontrolled diabetes with, for example, severe hyperglycemia (high blood glucose), 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 may lead to diabetic pre-coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or fruity-smelling breath
• if you have a serious infection
• if you have lost a large amount of fluid from your body (dehydration), e.g. due to severe or prolonged diarrhea or repeated vomiting
• if you have diabetic pre-coma
• if you have recently had a heart attack or have serious circulatory problems, such as “shock” or difficulty breathing
• if you drink alcohol excessively (either daily or occasionally)
• 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 functioning properly. The risk of developing lactic acidosis is also increased in uncontrolled diabetes, serious infections, prolonged fasting or alcohol consumption, dehydration (see further information below), liver problems, and any medical condition in which part of the body has reduced oxygen supply (such as acute and severe heart diseases).

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

Contact your doctor immediately for advice if:

• You are known to have a genetic mitochondrial disease (the components that produce energy inside cells), such as MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD).
• You experience any of the following symptoms after starting treatment with metformin: seizures, cognitive decline, difficulty with body movements, symptoms indicating nerve damage (e.g., pain or numbness), migraine, or deafness.

Temporarily stop taking Vokanamet if you have a condition that may lead to dehydration (significant loss of body fluids), such as severe vomiting, diarrhea, fever, heat exposure, or if you are drinking less fluid than usual. Consult your doctor for further instructions.

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

Symptoms of lactic acidosis include:

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• general feeling of discomfort with severe fatigue
• difficulty breathing
• decreased body temperature and heart rate

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

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

• to learn 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 condition
• if you experience rapid weight loss, feeling unwell or being unwell, stomach pain, excessive thirst, rapid and deep breathing, confusion, unusual drowsiness or fatigue, sweet smell on your breath, sweet or metallic taste in your mouth, or unusual odor in your urine or sweat, contact your doctor or go to the nearest hospital immediately. These symptoms may be signs of “diabetic ketoacidosis” – a rare but serious, sometimes potentially life-threatening condition that may occur in diabetes due to increased levels of “ketone bodies” in your urine or blood, detected in tests. The risk of developing “diabetic ketoacidosis” may be increased by prolonged fasting, excessive alcohol consumption, dehydration, sudden reduction in insulin dose, or increased insulin need due to major surgery or serious illness
• if you are undergoing major surgery or a procedure requiring prolonged fasting, ask your doctor whether you should stop taking Vokanamet and when you should restart it
• if you have ever had serious heart disease or a stroke
• if you are taking medicines to lower your blood pressure (antihypertensives) or have ever had low blood pressure (hypotension). See section “Other medicines and Vokanamet” for more information
• if you have ever had a lower limb amputation
• It is important that you regularly check your feet and follow any other foot care advice, as well as maintain adequate hydration as advised by your doctor. Inform your doctor immediately if you notice any wounds or discoloration, or if you experience any sensitivity or pain in your feet. Some studies suggest that taking canagliflozin may have contributed to an increased risk of lower limb amputations (mainly amputations of toes and midfoot)
• Contact your doctor immediately if you develop a combination of symptoms such as pain, tenderness, redness, or swelling in the genital area or the area between the genitals and the anus, with fever or general malaise. These symptoms could indicate a rare but serious, even potentially fatal, infection called necrotizing fasciitis of the perineum or Fournier’s gangrene, which destroys tissue under the skin. Fournier’s gangrene requires immediate treatment
• if you have symptoms of a genital fungal infection such as irritation, itching, unusual discharge, or odor
• if you have a serious kidney or urinary tract infection with fever. Your doctor may ask you to stop taking Vokanamet until you recover.

Kidney function

Your kidneys will be checked with a blood test before you start taking Vokanamet. During treatment with Vokanamet, your doctor will monitor your kidney function at least once a year, or more frequently if you are elderly and/or if your kidney function is worsening.

Surgery

If you need to undergo major surgery, you must stop taking Vokanamet during the procedure and for some time afterward. Your doctor will decide when to stop and when to restart treatment with Vokanamet.

Your doctor will decide whether you need another treatment to control your blood sugar while you are not taking Vokanamet. It is important to follow your doctor’s instructions exactly.

Glucose in urine

Because of 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 or adolescents under 18 years of age, as there is no data available for these patients.

Other medicines and Vokanamet

If you need to receive an intravenous injection of an iodine-containing contrast agent, for example during an X-ray or scan, you must stop taking Vokanamet before or at the time of the injection. Your doctor will decide when to stop and when to restart treatment with Vokanamet.

Tell your doctor if you are taking, have recently taken, or might need to 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 excessively low blood sugar levels (hypoglycemia)

• medicines that increase urine production (diuretics)

• St. John’s wort (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 reduce blood cholesterol levels). See section 3, “How to take this medicine”

• digoxin or digitoxin (medicines used for certain heart conditions). If you take Vokanamet, the concentration of digoxin or digitoxin in your blood may need to be monitored

• dabigatran (an anticoagulant medicine that reduces the risk of blood clots)

• medicines containing alcohol. See section “Vokanamet with alcohol”

• cimetidine (a medicine used to treat stomach problems)

• corticosteroids (used to treat a range of conditions, such as severe skin inflammation or asthma) taken orally, by injection, or inhaled

• 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 become pregnant, consult your doctor or pharmacist before using or continuing to use this medicine.

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

You should not take this medicine while breastfeeding. Consult your doctor whether you should stop taking this medicine or stop breastfeeding.

Driving and using machines

The effect of Vokanamet on the ability to drive, ride a bicycle, or use tools or machines is negligible or none. 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 glipizida) or insulin may increase the risk of low blood sugar levels (hypoglycemia). Symptoms include blurred vision, tingling lips, tremor, sweating, paleness, mood changes, anxiety, or confusion. These may affect your ability to drive, ride a bicycle, or use tools or machines. Inform your doctor as soon as possible if you experience 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 given by your doctor or pharmacist for taking this medicine. If in doubt, consult your doctor or pharmacist again.

How much to take

• The dose of Vokanamet is one tablet twice daily.
• The strength of Vokanamet you should take will depend on your condition and the amount of canagliflozin and metformin needed to control your blood sugar.
• Your doctor will prescribe the appropriate 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 each day. This will help you remember to take it.
• If your doctor has prescribed this medicine together with a cholesterol-lowering medicine such as colestyramine, you should take this medicine at least 1 hour before or between 4 and 6 hours after taking the cholesterol-lowering medicine.

Your doctor may prescribe Vokanamet together with another medicine to lower glucose. Remember to take all your medicines as directed by your doctor to achieve 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 regarding diet and exercise. In particular, if you are following a diabetic weight-control diet, you should continue it while taking this medicine.

If you take more Vokanamet than you should

Since Vokanamet contains metformin, taking more than the prescribed amount may cause lactic acidosis. If this occurs, you may require immediate hospital treatment, as lactic acidosis can lead to coma. Symptoms of lactic acidosis include vomiting, stomach pain, muscle cramps, a general feeling of malaise with severe tiredness or difficulty breathing. Other symptoms include lowered body temperature and heart rate. Stop taking this medicine immediately and contact a doctor or the nearest hospital right away (see section 2). Take the medicine package 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 almost time for your 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 level may rise if you stop taking this medicine. Do not stop taking this medicine without first talking to your doctor.

If you have any further questions about 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 everyone experiences them.

Stop taking Vokanamet and speak with 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, which may 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 in 10,000 users), but very serious, adverse effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking Vokanamet and speak with 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):

• increased levels of “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 tiredness
• sweet smell on your breath, sweet or metallic taste in your mouth, or a different smell in your urine or sweat.

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

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

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

Possible symptoms of dehydration include:

• feeling dizzy or lightheaded
• loss of consciousness (fainting) or feeling dizzy or faint when standing up
• very dry or sticky mouth, intense thirst
• unusual tiredness or weakness
• little or no urination
• rapid heartbeat.

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

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

• low blood sugar (hypoglycaemia) – when taking this medicine together with insulin or a sulphonylurea (such as glimepiride or glipizide)

Possible symptoms of low blood sugar include:

• blurred vision
• tingling around the lips
• trembling, sweating, paleness
• mood changes or feelings of anxiety or confusion.

Your doctor will explain how to treat low blood sugar and what to do if you experience 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 urine (urinating)
  • pain in your back or side.

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

Other adverse effects 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 output, urgent need to urinate, need to urinate at night)
• constipation
• feeling thirsty
• feeling sick (nausea)
• blood tests may show changes in lipid levels (cholesterol) and increased red blood cell count (haematocrit).

Uncommon (may affect up to 1 in 100 people)

• skin rash or redness – this may cause itching and include raised bumps, weeping rash or blisters
• hives
• blood tests may show changes related to kidney function (increased creatinine or urea) or increased potassium
• blood tests may show increased levels of phosphate in your blood
• bone fracture
• kidney failure (mainly as a consequence of losing a large amount of fluid from your body)
• lower-limb amputations (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)

• necrotising 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 not described for canagliflozin:

• very common: feeling sick (nausea), being sick (vomiting), diarrhoea, stomach pain and loss of appetite
• common: metallic taste (taste disturbance), decreased levels of vitamin B12 (may cause anaemia – low count of red blood cells)
• very rare: abnormal liver function tests, hepatitis (a liver problem) and itching.

Reporting of adverse effects

If you experience any adverse effect, talk to 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 help provide 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 expiry date stated on the bottle and the carton following EXP. The expiry date refers to the last day of the month indicated.

Do not store above 30°C.

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Vokanamet

• The active substances 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.

• The other components are:

  • 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 contents of the pack

• Vokanamet 50 mg/850 mg film-coated tablets (tablets) are pink, capsule-shaped, 20 mm in length, 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 in length, 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 in length, 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 in length, with "CM" engraved on one side and "611" on the other side.

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

Some pack sizes may not 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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: {month YYYY}.

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu, and on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).