XIGDUO 5 mg/850 mg FILM-COATED TABLETS

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. The symptoms include stomach pain, rapid and deep breathing, drowsiness, or an unusual fruity odor to your breath.
• if you have severe kidney function 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 consumption, dehydration (see more information below), liver problems, and any medical condition in which a part of your body has a reduced supply of oxygen (such as acute and severe 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 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 fatigue
• difficulty breathing
• decrease in body temperature and heart rate

Lactic acidosis is a medical emergency and should 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 indicative of nerve damage (e.g., pain or numbness), migraine, and hearing loss.

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

• if you have “type 1 diabetes” - the type that usually appears when you are young and your body does not produce any insulin. Xigduo should not be used to treat this disease.
• if you experience rapid weight loss, have nausea or vomiting, have stomach pain, excessive thirst, rapid and deep breathing, confusion, drowsiness, and unusual fatigue, 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 can cause dehydration (lose too much body fluid). Possible signs of dehydration are included in section 4. Inform your doctor before starting 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 a period after it. 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 not sure), 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 the 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 should 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 older person and/or if your kidney function is worsening.

Glucose in urine

Due to how 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, in the context of 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 consumption 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 no or 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 of administration of this medicine given to you by your doctor. In case of doubt, consult your doctor or pharmacist again.

How much to take

• The amount of this medicine that you will take varies depending on your condition and the doses that you are currently taking of metformin and/or individual tablets of dapagliflozin and metformin. Your doctor will tell you exactly which concentration 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 medicine(s) taken by mouth or given by injection, 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 dietary and exercise recommendations given to you by your doctor, pharmacist, or nurse. In particular, if you are following a weight-control diet for diabetics, 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 fatigue, 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). Bring the medicine pack with you.

If you forget to take Xigduo

If you forget 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 follow 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,which 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, which 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
• 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, which occurs frequently (may affect up to 1 in 10 people)

These are the signs of a serious urinary tract infection:

• fever and/or chills
• burning sensation when urinating
• back pain or side pain

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

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

• Low blood sugar levels (hypoglycemia), which is observed very frequently (may affect more than 1 in 10 people) – when taking this medicine with a sulfonylurea or other medicines that lower 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
• mood changes or feeling of confusion

Your doctor will explain how to treat low blood sugar levels 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 common

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

Common

• 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 (symptoms may include extreme fatigue, red and painful tongue, tingling, or pale or yellowish skin). Your doctor may request some tests to determine 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 fluid loss from the body (dehydration, signs may include very dry or sticky mouth, reduced 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)

Rare

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

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects 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 Xigduo

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date stated 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 any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Xigduo Composition

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

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

• 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

• Xigduo 5 mg/850 mg film-coated tablets are brown, oval, 9.5 x 20 mm. They are engraved with “5/850” on one side and “1067” on the other
• Xigduo 5 mg/1,000 mg film-coated tablets 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, 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 Last Revision of this Leaflet:

Other Sources of Information

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