XIGDUO 5 mg/1000 mg FILM-COATED TABLETS

Introduction

Package Leaflet:information for the patient

Xigduo 5mg/850mg film-coated tablets

Xigduo 5mg/1,000mg film-coated tablets

dapagliflozin/metformin hydrochloride

Read all of this leaflet carefully before you start takingthismedicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Xigduo and what is it used for
2. What you need to know before you take Xigduo
3. How to take Xigduo
4. Possible side effects
5. Storing Xigduo
6. Contents of the pack and other information

1. What is Xigduo and what is it used for

This medicine contains two different active substances called dapagliflozin and metformin. Both belong to a group of medicines called “oral antidiabetics”. These are medicines taken by mouth for diabetes.

Xigduo is used for a type of diabetes called “type 2 diabetes” in adult patients (18 years or older) and normally occurs when you are older. If you have type 2 diabetes, your pancreas does not produce enough insulin or your body is not able to use the insulin it produces properly. This leads to a high level of sugar (glucose) in your blood.

• Dapagliflozin works by removing excess sugar from your body through urine and decreasing the amount of sugar in your blood. It may also help prevent heart disease.
• Metformin mainly works by inhibiting glucose production in the liver.

To treat diabetes:

• This medicine is taken in combination with diet and exercise.
• This medicine is used if your diabetes cannot be controlled with other medicines used to treat diabetes.
• Your doctor may ask you to take this medicine alone or with other medicines to treat diabetes. It may be another oral medicine and/or an injectable medicine, such as insulin or a GLP-1 receptor agonist (helps your body increase insulin production when your blood sugar is high).
• If you are already taking dapagliflozin and metformin as separate tablets, your doctor may ask you to switch to this medicine. To avoid overdose, do not continue taking the separate dapagliflozin and metformin tablets if you are taking Xigduo.

It is important that you continue to follow the diet and exercise recommendations given to you by your doctor, pharmacist, or nurse.

2. What you need to know before you take Xigduo

Do not take Xigduo:

• if you are allergic to dapagliflozin, metformin, or any of the other ingredients of this medicine (listed in section 6).
• if you have ever had diabetic coma.
• 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 severe kidney impairment.
• if you have a severe infection.
• if you have lost a lot of water from your body (dehydration), for example, due to prolonged or severe diarrhea or if you have vomited several times in a row.
• if you have recently had a heart attack or if you have heart failure or any serious blood circulation problems or breathing difficulties.
• if you have liver problems.
• if you drink large amounts of alcohol, every day or only occasionally (see section “Taking Xigduo with alcohol”).

Do not take this medicine if any of the above applies to you.

Warnings and precautions

Risk of lactic acidosis

Xigduo 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 intake, dehydration (see more information below), liver problems, and any medical condition in which a part of your body has a reduced oxygen supply (such as severe and acute heart disease).

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

Stop taking Xigduo for a short period 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 Xigduo and contact a doctor or the nearest hospital immediately if you experience any of the symptoms that lactic acidosis can cause, as this condition can lead to a coma.

The symptoms of lactic acidosis include:

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

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

Consult your doctor quickly if:

• You know you have a genetic disease that affects the mitochondria (the energy-producing components within cells), such as MELAS syndrome (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) or Maternally Inherited Diabetes and Deafness (MIDD).

Experiences any of the following symptoms after starting treatment with metformin: convulsions, cognitive impairment, difficulty with body movements, symptoms indicating nerve damage (e.g., pain or numbness), migraine, and hearing loss.

Consult your doctor, pharmacist, or nurse before you start taking Xigduo and during treatment:

• if you have “type 1 diabetes” - the type that usually occurs when you are young and your body does not produce any insulin. Xigduo should not be used to treat this condition.
• if you experience rapid weight loss, have nausea or vomiting, have stomach pain, excessive thirst, rapid and deep breathing, confusion, drowsiness, and unusual tiredness, sweet smell on your breath, a sweet or metallic taste in your mouth, or a different smell in your urine or sweat, contact a doctor or the nearest hospital immediately. These symptoms may be a sign of “diabetic ketoacidosis” - a rare but serious, potentially life-threatening problem that occurs with diabetes due to an increase in “ketone bodies” in your urine or blood, which is detected in laboratory tests. The risk of developing diabetic ketoacidosis may be increased with prolonged fasting, excessive alcohol consumption, dehydration, sudden reductions in insulin dose, or a greater need for insulin due to major surgery or serious illness.
• if you have any kidney problems. Your doctor will check your kidney function.
• if you have very high blood sugar levels that may cause dehydration (losing too much body fluid). Possible signs of dehydration are included in section 4. Inform your doctor before you start taking this medicine if you have any of these signs.
• if you are taking medicines to lower your blood pressure (antihypertensives) or have a history of low blood pressure (hypotension). More information is included later in “Taking Xigduo with other medicines”.
• if you frequently have urinary tract infections. This medicine may cause urinary tract infections, and your doctor may want to monitor you more closely. Your doctor may consider temporarily changing your treatment if you develop a severe infection.

If you need to undergo major surgery, you should stop taking Xigduo during the procedure and for some time after. Your doctor will decide when you should stop taking Xigduo and when you can restart it.

It is important that you regularly check your feet and follow any other foot care advice given to you by your healthcare professional.

If any of the above applies to you (or you are unsure), talk to your doctor, pharmacist, or nurse before taking this medicine.

Consult your doctor immediately if you experience a combination of symptoms of pain, tenderness, redness, or swelling of the genitals or the area between the genitals and anus, with fever or general feeling of being unwell. These symptoms could be a sign of a rare but serious, potentially life-threatening infection called necrotizing fasciitis of the perineum or Fournier's gangrene, which destroys tissue under the skin. Fournier's gangrene must be treated immediately.

Kidney function

During treatment with Xigduo, 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.

Glucose in urine

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

Children and adolescents

This medicine is not recommended for children and adolescents under 18 years of age, as it has not been studied in these patients.

Other medicines and Xigduo

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

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 Xigduo. It is especially important to mention the following:

• if you are taking a medicine used to remove fluid from the body (diuretic).
• if you are taking other medicines that lower the amount of sugar in the blood, such as insulin or a “sulfonylurea” type medicine. Your doctor may decide to reduce the dose of these medicines to avoid low blood sugar levels (hypoglycemia).
• if you are taking lithium, as Xigduo may reduce the amount of lithium in your blood.
• if you are taking cimetidine, a medicine used to treat stomach problems.
• if you are using bronchodilators (beta-2 agonists) used to treat asthma.
• if you are using corticosteroids (used to treat inflammation in diseases such as asthma and arthritis) given orally, injected, or inhaled.
• if you are using medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib).
• if you are using certain medicines to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).

Taking Xigduo with alcohol

Avoid excessive alcohol intake while taking Xigduo, 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 this medicine. You should stop taking this medicine if you become pregnant, as it is not recommended during the second and third trimesters of pregnancy (the last six months). Consult your doctor about the best way to control your blood sugar during pregnancy.

Consult your doctor if you want to breastfeed or are breastfeeding before taking this medicine. You should not use this medicine during breastfeeding. Metformin passes into breast milk in small amounts. It is not known if dapagliflozin passes into breast milk.

Driving and using machines

This medicine has a negligible influence on the ability to drive and use machines. Taking it with other medicines that lower the amount of sugar in the blood, such as insulin or a “sulfonylurea” type medicine, may cause low blood sugar levels (hypoglycemia), which can cause symptoms such as weakness, dizziness, increased sweating, rapid heartbeat, vision changes, or difficulty concentrating, which can affect your ability to drive or use machines. Do not drive or use tools or machines if you start to feel these symptoms.

Sodium content

This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially “sodium-free”.

3. How to take Xigduo

Follow exactly the instructions for taking this medicine given to you by your doctor. If you are unsure, consult your doctor or pharmacist again.

How much to take

• The amount of this medicine you take will vary depending on your condition and the doses you are currently taking of metformin and/or separate dapagliflozin and metformin tablets. Your doctor will tell you exactly which strength of this medicine to take.
• The recommended dose is one tablet twice a day.

How to take this medicine

• Swallow the tablet whole with a half glass of water.
• Take the tablet with food. This is to reduce the risk of stomach side effects.
• Take your tablet twice a day, one in the morning (breakfast) and one in the evening (dinner).

Your doctor may prescribe this medicine for you to take with another medicine(s) to lower the amount of sugar in your blood. These may be oral medicine(s) and/or injectable medicine(s), such as insulin or a GLP-1 receptor agonist. Remember to take these other medicine(s) as instructed by your doctor. This will help you get the best results for your health.

Diet and exercise

To control your diabetes, you should continue with diet and exercise, even when taking this medicine. Therefore, it is important that you continue to follow the diet and exercise recommendations given to you by your doctor, pharmacist, or nurse. In particular, if you are following a weight control diet for diabetes, continue with it while taking this medicine.

If you take more Xigduo than you should

If you take more Xigduo tablets than you should, you may experience lactic acidosis. The symptoms of lactic acidosis include having a lot of nausea or vomiting, stomach pain, muscle cramps, intense tiredness, or difficulty breathing. If this happens to you, you may need immediate hospital treatment, as lactic acidosis can lead to a coma. 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 Xigduo

If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose of this medicine to make up for missed doses.

If you stop taking Xigduo

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

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 Xigduo and consult a doctor immediately if you notice any of these serious or potentially serious adverse effects:

• Lactic acidosis,occurs rarely (may affect up to 1 in 10,000 people)

Xigduo may cause a very rare but very serious adverse effect called lactic acidosis (see section 2 “Warnings and Precautions”). If this happens to you, you must stop taking Xigduo and contact a doctor or the nearest hospital immediately, as lactic acidosis can lead to coma.

Contact a doctor or the nearest hospital immediately if you experience any of the following adverse effects:

• Diabetic ketoacidosis, has been observed rarely (may affect up to 1 in 1,000 people)

These are the signs of diabetic ketoacidosis (see also section 2 “Warnings and Precautions”):

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

This can occur despite blood glucose levels. Your doctor should decide whether to temporarily or permanently interrupt your treatment with Xigduo.

• Necrotizing fasciitis of the perineumor Fournier's gangrene, a serious infection of the soft tissues of the genitals or the area between the genitals and the anus, seen very rarely.

Stop taking Xigduo and consult a doctor as soon as possible if you notice any of the following serious or potentially serious adverse effects:

• Urinary tract infection, occurs frequently (may affect up to 1 in 10 people).

These are the signs of a serious urinary tract infection:

• fever and/or chills
• feeling of burning when urinating
• back pain or side pain.

Although it is rare, if you see blood in your urine, inform your doctor immediately.

Contact a doctor as soon as possible if you experience any of the following adverse effects:

• Decrease in blood sugar levels (hypoglycemia), is observed very frequently (may affect more than 1 in 10 people) – when taking this medicine with a sulfonylurea or other medicines that reduce blood sugar levels, such as insulin.

The signs of low blood sugar are:

• chills, sweating, feeling of great anxiety, rapid heartbeat
• feeling of hunger, headache, vision changes
• change in mood or feeling of confusion.

Your doctor will explain how to treat low blood sugar and what to do if you experience any of the above symptoms. If you have symptoms of low blood sugar, take glucose tablets, a sugary snack, or drink a fruit juice. Measure your blood sugar level, if possible, and rest.

Other adverse effects include:

Very frequent

• nausea, vomiting
• diarrhea or stomach pain
• loss of appetite

Frequent

• genital infections (candidiasis) of the penis or vagina (signs may include irritation, itching, and abnormal discharge or odor)
• back pain
• difficulty urinating, increased urine production, or need to urinate more frequently
• changes in cholesterol or lipid levels in the blood (observed in laboratory tests)
• increase in red blood cells in the blood (observed in laboratory tests)
• decrease in renal clearance of creatinine (observed in laboratory tests) at the start of treatment
• changes in taste
• dizziness
• rash
• low levels of vitamin B12 in the blood or decreased (symptoms may include extreme fatigue, red and sore tongue, tingling, or pale or yellowish skin). Your doctor may request some tests to discover the cause of your symptoms because some of them can also be caused by diabetes or other health problems unrelated to this medicine.

Uncommon(may affect up to 1 in 100 people)

• excessive loss of body fluids (dehydration, signs may include very dry or sticky mouth, decreased or absent urination, or rapid heartbeat)
• thirst
• constipation
• nocturnal awakenings due to need to urinate
• dry mouth
• weight loss
• increase in creatinine (observed in blood tests) at the start of treatment
• increase in urea (observed in blood tests)

Very rare

• abnormal liver function test results, liver inflammation (hepatitis)
• skin redness (erythema), itching, or pruritus (hives)
• kidney inflammation (tubulointerstitial nephritis)

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 that does not appear 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 Xigduo

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

Do not use this medicine after the expiration date that appears on the blister or packaging after EXP/CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

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

6. Package Contents and Additional Information

Xigduo Composition

• The active ingredients are dapagliflozin and metformin hydrochloride (HCl metformin).

Each film-coated tablet (tablet) of Xigduo 5 mg/850 mg contains dapagliflozin propanediol monohydrate equivalent to 5 mg of dapagliflozin and 850 mg of metformin hydrochloride.

Each film-coated tablet (tablet) of Xigduo 5 mg/1,000 mg contains dapagliflozin propanediol monohydrate equivalent to 5 mg of dapagliflozin and 1,000 mg of metformin hydrochloride.

• The other ingredients are:

• tablet core: hydroxypropylcellulose (E463), microcrystalline cellulose (E460(i)), magnesium stearate (E470b), sodium carboxymethylcellulose (type A).
• film coating: polyvinyl alcohol (E1203), macrogol 3350 (E1521), talc (E553b), titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172) (only Xigduo 5 mg/850 mg).

Product Appearance and Package Contents

• The film-coated tablets of Xigduo 5 mg/850 mg are brown, oval, 9.5 x 20 mm. They are engraved with “5/850” on one side and “1067” on the other.
• The film-coated tablets of Xigduo 5 mg/1,000 mg are yellow, oval, 10.5 x 21.5 mm. They are engraved with “5/1000” on one side and “1069” on the other.

Xigduo 5 mg/850 mg film-coated tablets and Xigduo 5 mg/1,000 mg film-coated tablets are available in PVC/PCTFE/Alu blisters. The package sizes are 14, 28, 56, and 60 film-coated tablets in non-perforated blisters, packages of 60x1 film-coated tablets in perforated unit-dose blisters, and multiple packages of 196 (2 packages of 98) film-coated tablets in non-perforated blisters.

Not all package sizes may be marketed in your country.

Marketing Authorization Holder

AstraZeneca AB

SE-151 85 Södertälje

Sweden

Manufacturer

AstraZeneca AB

Gärtunavägen

SE-152 57 Södertälje

Sweden

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

Date of the last revision of thisleaflet:

Other sources of information

Detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu