Xigduo 5 mg/850 mg film-coated tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

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 taking this medicine, as 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. Do not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, talk to your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Xigduo is and what it is used for

This medicine contains two different active substances called dapagliflozin and metformin. Both belong to a group of medicines known as "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 of age or older), which typically develops later in life. If you have type 2 diabetes, your pancreas does not produce enough insulin or your body is unable to use the insulin it produces effectively. This leads to high levels of sugar (glucose) in your blood.

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

To treat diabetes:

• This medicine should be taken together with diet and exercise.
• This medicine is used when your diabetes cannot be controlled with other medicines used to treat diabetes.
• Your doctor may instruct you to take this medicine alone or together with other diabetes medicines. These may include another oral medicine and/or an injectable medicine, such as insulin or a GLP-1 receptor agonist (which 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 separate dapagliflozin and metformin tablets while taking Xigduo.

It is important that you continue to follow the dietary and exercise advice provided by your doctor, pharmacist, or nurse.

2. What you need to know before taking 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, for example, with severe hyperglycemia (high blood glucose), nausea, vomiting, diarrhea, rapid weight loss, lactic acidosis (see “Risk of lactic acidosis” below), or ketoacidosis. Ketoacidosis is a disorder in which substances called “ketone bodies” accumulate in the blood, which may lead to diabetic pre-coma. Symptoms include stomach pain, rapid deep breathing, drowsiness, or fruity-smelling breath.
• if you have severely reduced kidney function.
• if you have a serious infection.
• if you have lost a large amount of body water (dehydration), e.g. due to prolonged or severe diarrhea, or if you have vomited repeatedly.
• if you have recently had a heart attack or if you have heart failure or a serious circulatory problem or difficulty breathing.
• if you have liver problems.
• if you consume large amounts of alcohol, every day or occasionally (see section “Taking Xigduo with alcohol”).

Do not take this medicine if any of the above apply 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 functioning properly. The risk of developing lactic acidosis is also increased in uncontrolled diabetes, serious infections, prolonged fasting or alcohol intake, dehydration (see more information below), liver problems, and any medical condition in which part of the body has reduced oxygen supply (such as acute and serious heart conditions).

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

Stop taking Xigduo 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 are drinking less fluid than normal. Consult your doctor for further instructions.

Stop taking Xigduo and contact a doctor or 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 extreme tiredness
• difficulty breathing
• reduced body temperature and heart rate

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

Contact your doctor promptly for guidance if:

• You are known to have a hereditary genetic disease affecting mitochondria (the energy-producing components inside cells), such as MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) or Maternally Inherited Diabetes and Deafness (MIDD).
• You develop any of the following symptoms after starting metformin treatment: seizures, cognitive decline, difficulty with body movements, symptoms indicating nerve damage (e.g., pain or numbness), migraine, or deafness.

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 produces no insulin. Xigduo should not be used to treat this condition.
• if you experience rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, rapid deep breathing, confusion, drowsiness, unusual tiredness, sweet-smelling breath, a sweet or metallic taste in the mouth, or a different odor in your urine or sweat, contact a doctor or the nearest hospital immediately. These symptoms may indicate “diabetic ketoacidosis” – a rare but serious, sometimes life-threatening condition occurring in diabetes due to an increase in “ketone bodies” in your urine or blood, detectable in laboratory tests. The risk of developing diabetic ketoacidosis may be increased by prolonged fasting, excessive alcohol consumption, dehydration, sudden reductions in insulin dose, or increased insulin needs 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 glucose levels that may cause dehydration (loss of too much fluid from the body). Possible signs of dehydration are listed 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 provided later in “Taking Xigduo with other medicines.”
• if you frequently get 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 serious infection.

If you need to undergo major surgery, you must stop taking Xigduo during the procedure and for a period afterward. Your doctor will decide when to interrupt and when to restart treatment with Xigduo.

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

If any of the above situations apply to you (or you are unsure), speak with your doctor, pharmacist, or nurse before taking this medicine.

Contact your doctor immediately if you develop a combination of symptoms such as pain, tenderness, redness, or swelling of the genitals or the area between the genitals and the anus, along 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 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 elderly 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 receive an intravenous injection of an iodine-containing contrast agent, for example, during an X-ray or scan, you must stop taking Xigduo before or at the time of the injection. Your doctor will decide when to interrupt and when to restart treatment with Xigduo.

Inform your doctor if you are taking, have recently taken, or might need to take any other medicine. You may need more frequent blood glucose and kidney function tests, or your doctor may need to adjust your 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 blood sugar, such as insulin or a “sulfonylurea” 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 the 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 conditions such as asthma and arthritis), whether taken 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 plan to become pregnant, consult your doctor or pharmacist before taking this medicine. You should stop taking this medicine if you become pregnant, as its use is not recommended during the second and third trimesters of pregnancy (the last six months). Consult your doctor about the best way to control blood glucose during pregnancy.

Consult your doctor if you are breastfeeding or plan to breastfeed before taking this medicine. You must not use this medicine while breastfeeding. Metformin passes into human milk in small amounts. It is unknown whether dapagliflozin passes into breast milk.

Driving and using machines

This medicine has no or negligible influence on the ability to drive or use machines. However, taking it with other medicines that lower blood sugar, such as insulin or a “sulfonylurea” medicine, may cause very low blood sugar levels (hypoglycemia), which can cause symptoms such as weakness, dizziness, increased sweating, rapid pulse, vision disturbances, or difficulty concentrating, which may affect your ability to drive or use machines. Do not drive or operate tools or machinery if you begin to experience these symptoms.

Sodium content

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

3. How to take Xigduo

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

How much to take

• The dose of this medicine you will take varies depending on your condition and the doses of metformin and/or individual tablets of dapagliflozin and metformin you are currently taking. Your doctor will tell you exactly which strength of this medicine you should take.
• The recommended dose is one tablet twice daily.

How to take this medicine

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

Your doctor may prescribe this medicine together with other medicine(s) to lower your blood sugar levels. These may be oral medicines or injections, such as insulin or a GLP‑1 receptor agonist. Remember to take these other medicines exactly as instructed by your doctor. This will help you achieve the best possible health outcomes.

Diet and exercise

To control your diabetes, you must continue your diet and exercise regimen even while taking this medicine. It is therefore important that you continue to follow the dietary and exercise advice provided by your doctor, pharmacist, or nurse. In particular, if you are following a diabetic weight-control diet, continue with it while taking this medicine.

If you take more Xigduo than you should

If you take more Xigduo tablets than prescribed, you may experience lactic acidosis. Symptoms of lactic acidosis include severe nausea or vomiting, stomach pain, muscle cramps, extreme tiredness, or difficulty breathing. If this happens to you, you may require immediate hospital treatment, as lactic acidosis can lead to coma. Stop taking this medicine immediately and contact a doctor or the nearest hospital right away (see section 2). Take the medicine packaging 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 dosing schedule. Do not take a double dose of this medicine to make up for a missed dose.

If you stop taking Xigduo

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

If you have any further questions about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Stop taking Xigduo and consult a doctor immediately if you notice any of the following 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, 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”):

• 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 and tiredness
• sweet smell on your breath, a sweet or metallic taste in your mouth, or a different odour in your urine or sweat.

This may occur even when blood glucose levels are normal. Your doctor must decide whether to temporarily or permanently discontinue your treatment with Xigduo.

• 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, very rarely reported.

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
• burning sensation when urinating (urinating)
• back or side pain.

Although uncommon, 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:

• Decreased blood sugar levels (hypoglycaemia), observed very frequently (may affect more than 1 in 10 people) – when taking this medicine together with a sulphonylurea or other medicines that lower blood sugar levels, such as insulin.

Signs of low blood sugar include:

• chills, sweating, feeling very anxious, rapid heartbeat
• feeling hungry, headache, vision disturbances
• mood changes or feeling confused.

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

Other adverse effects include:

Very common

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

Common

• genital infections (candidiasis) of the penis or vagina (signs may include irritation, itching, and abnormal discharge or odour)
• back pain
• discomfort when urinating, increased amount of urine, or need to urinate more frequently
• changes in cholesterol or lipid levels in the blood (seen in blood tests)
• increase in the number of red blood cells in the blood (seen in blood tests)
• decrease in renal creatinine clearance (seen in blood tests) at the start of treatment
• changes in taste
• dizziness
• rash
• low or decreased vitamin B12 levels in the blood (symptoms may include extreme tiredness (fatigue), red and sore tongue (glossitis), tingling (paraesthesia), or pale or yellowish skin). Your doctor may order tests to determine the cause of your symptoms, as some of these may also be caused by diabetes or other unrelated health problems.

Uncommon (may affect up to 1 in 100 people)

• excessive loss of body fluids (dehydration, signs may include very dry or sticky mouth, little or no urination, or rapid heartbeat)
• thirst
• constipation
• waking up at night due to need to urinate
• dry mouth
• weight loss
• increase in creatinine (seen in blood tests) at the start of treatment
• increase in urea (seen in blood tests)

Very rare

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

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 Xigduo

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

Do not use this medicine after the expiry date stated on the blister or carton after EXP/EXP. The expiry date refers to 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 any unused medicine and its packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Xigduo

• The active substances 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 components are:

• tablet core: hypromellose (E463), microcrystalline cellulose (E460(i)), magnesium stearate (E470b), sodium carboxymethyl starch (type A).

• film coating: polyvinyl alcohol (E1203), macrogol 3350 (E1521), talc (E553b), titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172) (only in Xigduo 5 mg/850 mg).

Nature and contents of the container

• The film-coated tablets of Xigduo 5 mg/850 mg are brown, oval-shaped, measuring 9.5 x 20 mm. They are marked 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-shaped, measuring 10.5 x 21.5 mm. They are marked 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. Pack sizes are 14, 28, 56 and 60 film-coated tablets in non-perforated blister packs, packs of 60x1 film-coated tablets in single-dose perforated blisters, and multiple packs of 196 (2 packs of 98) film-coated tablets in non-perforated blisters.

Some pack sizes may not be marketed in your country.

Marketing Authorization Holder

AstraZeneca AB

SE-151 85 Södertälje

Sweden

Manufacturer responsible for batch release

AstraZeneca AB

Gärtunavägen

SE-152 57 Södertälje

Sweden

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 package leaflet:

Other sources of information

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