Komboglyze

Package leaflet: Information for the patient

Komboglyze 2.5 mg/850 mg film-coated tablets

saxagliptin/metformin hydrochloride
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What Komboglyze is and what it is used for

This medicine contains two different active substances called:
saxagliptin, belonging to a class of medicines known as DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors),
and
metformin, belonging to a class of medicines known as biguanides.
Both belong to a group of medicines called oral antidiabetics.
What Komboglyze is used for
This medicine is used to treat a type of diabetes called 'type 2 diabetes'.
How Komboglyze works
Saxagliptin and metformin work together to control blood sugar levels.
They increase insulin levels after meals and reduce the amount of sugar produced by the body. Together with diet and physical exercise, this medicine helps lower blood sugar levels. This medicine may be used alone or in combination with other antidiabetic medicines, including insulin.
To control diabetes, it is necessary to follow a diet and engage in physical exercise, even while taking this medicine. For this reason, it is important that you continue to follow your doctor’s or nurse’s advice regarding diet and physical activity.

2. What you need to know before taking Komboglyze

Do not take Komboglyze

• If you are allergic to saxagliptin, metformin, or to any of the other ingredients of this medicine (listed in Section 6).
• If you have ever had a severe allergic reaction (hypersensitivity) to any other similar medicine you take to control your blood sugar level. Symptoms of a severe allergic reaction may include:
• Skin rashes.
• Appearance of red spots on the skin (urticaria).
• Swelling of the face, lips, tongue, and throat, which may cause difficulty in breathing and swallowing. If you experience these symptoms, stop taking this medicine immediately and contact your doctor or nurse without delay.
• If you have ever had diabetic coma.
• If you have uncontrolled diabetes associated, for example, with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see below “Risk of lactic acidosis”) or ketoacidosis. Ketoacidosis is a condition in which substances called “ketone bodies” accumulate in the blood and may lead to diabetic pre-coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, and breath with an unusually fruity odour.
• If you have severely reduced kidney function or liver problems.
• If you have recently had a heart attack or heart failure, or have severe circulatory problems or breathing difficulties that could be signs of heart problems.
• If you have a severe infection or are dehydrated (your body has lost a lot of water).
• If you are breastfeeding (see also “Pregnancy and breastfeeding”).
• If you drink alcohol excessively (either daily or occasionally) (please see the section “Komboglyze and alcohol”).

Do not take this medicine if you have any of the conditions listed above. If you are unsure, speak with your doctor or pharmacist before taking this medicine.

Warnings and precautions

Risk of lactic acidosis

Komboglyze may cause a very rare but very serious side effect called lactic acidosis, particularly if your kidneys are not functioning properly. The risk of developing lactic acidosis is higher in the presence of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see below for further information), liver problems, or any other medical condition characterised by reduced oxygen supply to part of the body (such as in severe heart disease).

If you have any of the medical conditions described above, consult your doctor for further instructions.

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

If you experience any of the symptoms of lactic acidosis, stop taking Komboglyze and seek immediate medical attention at your nearest doctor or hospital, as lactic acidosis can lead to coma.
Symptoms of lactic acidosis include:

• vomiting
• stomach ache (abdominal pain)
• muscle cramps
• a general feeling of discomfort associated with severe fatigue
• difficulty breathing
• reduced body temperature and slower heart rate

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

Consult your doctor or pharmacist before taking this medicine:

• If you have type 1 diabetes (your body does not produce insulin). This medicine should not be used to treat this condition.
• If you have or have had a disease of the pancreas.
• If you are taking insulin or an antidiabetic medicine known as a “sulphonylurea”, your doctor may consider it necessary to reduce the dose of insulin or sulphonylurea when taken together with this medicine, in order to avoid low blood sugar levels.
• If you have had allergic reactions to any other medicine taken to control your blood sugar level.
• If you have a disease or are taking medicines that may lower your defences against infections.
• If you have ever had heart failure or have other risk factors for developing heart failure, such as kidney problems. Your doctor will inform you about the signs and symptoms of heart failure. Contact your doctor, pharmacist, or nurse immediately if you notice any of these symptoms. Symptoms may include, but are not limited to, increasing shortness of breath, rapid weight gain, swelling of the feet (pedal oedema).

If you are scheduled for major surgery, you must stop taking Komboglyze during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with Komboglyze.

Skin lesions are a common complication of diabetes. Skin rash has been observed with saxagliptin and with some antidiabetic medicines in the same class as saxagliptin. Follow the recommendations given to you by your doctor or nurse regarding skin and foot care. Contact your doctor if blisters appear on your skin, as this could be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop taking Komboglyze.

If you have any of the problems listed above, or if you have any doubts, speak with your doctor or pharmacist before taking this medicine.

Tests or monitoring of kidney function

During treatment with this medicine, your doctor will check how well your kidneys are working at least once a year, or more frequently if you are elderly and/or if kidney function worsens.

Children and adolescents

Komboglyze is not indicated for use in children and adolescents under 18 years of age. It is not known whether this medicine is safe and effective when used in children and adolescents under 18 years of age.

Other medicines and Komboglyze

If you are due to receive an injection of iodinated contrast medium into the bloodstream, for example for an X-ray procedure, you must stop taking Komboglyze before or during the injection. Your doctor will decide when to stop and when to restart treatment with Komboglyze.

Inform your doctor if you are currently taking, have recently taken, or might take any other medicine. You may need to have more frequent blood glucose and kidney function tests, or your doctor may decide to adjust the dose of Komboglyze. It is particularly important to mention the following:

• cimetidine, a medicine used to treat stomach problems.
• ketoconazole, used to treat fungal infections.
• bronchodilators (beta-2 agonists), used to treat asthma.
• diltiazem, used for high blood pressure.
• rifampicin, an antibiotic used to treat infections such as tuberculosis.
• corticosteroids, used to treat inflammatory diseases such as asthma and arthritis.
• carbamazepine, phenobarbital, or phenytoin, used to control seizures (epileptic fits) or chronic pain.
• medicines that increase urine production (diuretics).
• medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib).
• some medicines used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).

If you are taking any of the medicines listed above, or if you have any doubts, speak with your doctor or pharmacist before taking this medicine.

Komboglyze and alcohol

Avoid excessive alcohol consumption during treatment with Komboglyze, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”).

Pregnancy and breastfeeding

Do not take this medicine if you are pregnant or planning to become pregnant, as the medicine may affect the baby.

Do not take this medicine if you are breastfeeding or think you may need to breastfeed, as metformin passes into breast milk in small amounts.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Saxagliptin and metformin have negligible influence on the ability to drive or use machines. However, hypoglycaemia may affect the ability to drive and use machines or work with safety devices, and there is a risk of hypoglycaemia when taking this medicine in combination with medicines known to cause hypoglycaemia, such as insulin and sulphonylureas.

3. How to take Komboglyze

Always take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
If your doctor prescribes this medicine together with a sulphonylurea or insulin, remember to take that other medicine exactly as directed by your doctor to achieve the best results for your health.

How much to take

• The dose of this medicine you should take depends on your condition and the doses of metformin and/or single saxagliptin and metformin tablets you are already taking. Your doctor will tell you the exact dose of this medicine to take.
• The recommended dose is one tablet twice daily. If you have reduced kidney function, your doctor may prescribe you a lower dose.

How to take this medicine

• Take this medicine by mouth.
• Take it with meals to reduce the likelihood of stomach problems.

Diet and exercise
To control diabetes, it is necessary for you to follow a diet and engage in physical activity, even while taking this medicine. Therefore, it is important to continue following your doctor’s or nurse’s advice regarding diet and exercise. In particular, if you are following a low-calorie diet to control your weight, continue it during treatment with this medicine.

If you take more Komboglyze than you should
If you take more Komboglyze tablets than you should, contact your doctor immediately or go to hospital. Take the medicine with you.

If you forget to take Komboglyze

• If you forget to take a dose of this medicine, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take the next dose at the scheduled time.
• Do not take a double dose of this medicine to make up for a forgotten dose.

If you stop taking Komboglyze
Continue taking this medicine until your doctor tells you to stop. This helps keep your blood sugar level under control.
If you have any doubts about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking this medicine and contact your doctor immediately if you experience any of the
following serious side effects:

• Lactic acidosis: Komboglyze may cause a very rare (may affect up to 1 in 10,000 people) but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking Komboglyze and seek immediate medical attention at the nearest doctor or hospital, because lactic acidosis can lead to coma.
• Severe and persistent abdominal pain (in the stomach area), possibly radiating to the back, along with nausea and vomiting, as these may be signs of an inflamed pancreas (pancreatitis).

Contact your doctor if you experience any of the following side effects:

• Severe joint pain

Other side effects of Komboglyze include:
Common (may affect up to 1 in 10 people)

• headache
• muscle pain (myalgia)
• feeling unwell or indigestion (dyspepsia)
• urinary tract infection
• upper respiratory tract infection
• inflammation of the nose or throat, such as cold symptoms or sore throat
• inflammation of the stomach (gastritis) or intestine, sometimes due to infection (gastroenteritis)
• sinus infection, sometimes with pain and heaviness felt behind the cheeks and eyes (sinusitis)
• flatulence
• dizziness
• tiredness (fatigue)

Uncommon (may affect up to 1 in 100 people)

• joint pain (arthralgia)
• difficulty in achieving or maintaining an erection (erectile dysfunction)

Side effects during treatment with saxagliptin alone:
Common

• dizziness
• tiredness (fatigue)

Side effects during treatment with saxagliptin alone or in combination:
Not known (frequency cannot be estimated from the available data)

• constipation
• blisters on the skin (bullous pemphigoid)

Some patients experienced a slight decrease in the number of a certain type of white blood cells (lymphocytes), detected by blood tests when saxagliptin was used alone or in combination. In addition, some patients reported skin rash and skin reactions (hypersensitivity) while taking saxagliptin.
During post-marketing use of saxagliptin, additional adverse events have been reported, including severe allergic reactions (anaphylaxis), and swelling of the face, lips, tongue, and throat, which may cause difficulty breathing or swallowing. If you have an allergic reaction, stop taking this medicine immediately and contact your doctor without delay. Your doctor may prescribe a medicine to treat the allergic reaction and a different medicine for your diabetes.

Side effects during treatment with metformin alone:
Very common (may affect more than 1 in 10 people)

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

Common

• metallic taste in the mouth
• reduced or low levels of vitamin B12 in the blood: symptoms may include extreme tiredness (fatigue), sore and red tongue (glossitis), tingling (paraesthesia), or pale or yellowish skin. Your doctor may order certain tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other unrelated health problems.

Very rare

• liver problems (hepatitis)
• skin redness (rash) or itching

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Komboglyze

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and packaging after
EXP/Exp. The expiry date refers to the last day of that month.
Store below 25°C.
Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Komboglyze contains
The active substances are saxagliptin and metformin hydrochloride.
Each film-coated tablet contains 2.5 mg of saxagliptin (as hydrochloride) and 850 mg of
metformin hydrochloride.
The other components (excipients) are:

• Tablet core: povidone K30, magnesium stearate.
• Film coating: polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc (E553b), red iron oxide (E172), yellow iron oxide (E172).
• Printing ink: shellac, indigo carmine aluminum lake (E132).

Description of the appearance of Komboglyze and contents of the pack

• Komboglyze 2.5 mg/850 mg film-coated tablets (tablets) are light brown to brown, round tablets, with "2.5/850" printed on one side and "4246" on the other side, in blue ink.
• Komboglyze is available in non-perforated aluminum blisters. Packs contain 14, 28, 56 and 60 film-coated tablets in non-perforated blisters, multiple packs containing 112 (2 packs of 56) and 196 (7 packs of 28) film-coated tablets in non-perforated blisters, and 60x1 film-coated tablets in single-dose perforated blisters.

Not all pack 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
AstraZeneca UK Limited
Silk Road Business Park
Macclesfield
Cheshire
SK10 2NA
United Kingdom

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:
België/Belgique/Belgien Lietuva
AstraZeneca S.A./N.V. UAB AstraZeneca Lietuva
Tel: +32 2 370 48 11 Tel: +370 5 2660550
България Luxembourg/Luxemburg
АстраЗенека България ЕООД AstraZeneca S.A./N.V.
Тел.: +359 (2) 44 55 000 Tél/Tel: +32 2 370 48 11
Česká republika Magyarország
AstraZeneca Czech Republic s.r.o. AstraZeneca Kft.
Tel: +420 222 807 111 Tel.: +36 1 883 6500
Danmark Malta
AstraZeneca A/S Associated Drug Co. Ltd
Tlf: +45 43 66 64 62 Tel: +356 2277 8000
Deutschland Nederland
AstraZeneca GmbH AstraZeneca BV
Tel: +49 40 809034100 Tel: +31 85 808 9900
Eesti Norge
AstraZeneca AstraZeneca AS
Tel: +372 6549 600 Tlf: +47 21 00 64 00
Ελλάδα Österreich
AstraZeneca A.E. AstraZeneca Österreich GmbH
Τηλ: +30 2 106871500 Tel: +43 1 711 31 0
España Polska
AstraZeneca Farmacéutica Spain, S.A. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +34 91 301 91 00 Tel.: +48 22 245 73 00
France Portugal
AstraZeneca AstraZeneca Produtos Farmacêuticos, Lda.
Tél: +33 1 41 29 40 00 Tel: +351 21 434 61 00
Hrvatska România
AstraZeneca d.o.o. AstraZeneca Pharma SRL
Tel: +385 1 4628 000 Tel: +40 21 317 60 41
Ireland Slovenija
AstraZeneca Pharmaceuticals (Ireland) DAC AstraZeneca UK Limited
Tel: +353 1609 7100 Tel: +386 1 51 35 600
Ísland Slovenská republika
Vistor hf. AstraZeneca AB, o.z.
Sími: +354 535 7000 Tel: +421 2 5737 7777
Italia Suomi/Finland
AstraZeneca S.p.A. AstraZeneca Oy
Tel: +39 02 00704500 Puh/Tel: +358 10 23 010
Κύπρος Sverige
Αλέκτωρ Φαρµακευτική Λτδ AstraZeneca AB
Τηλ: +357 22490305 Tel: +46 8 553 26 000
Latvija United Kingdom (Northern Ireland)
SIA AstraZeneca Latvija AstraZeneca UK Ltd
Tel: +371 67377100 Tel: +44 1582 836 836

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

Patient Information Leaflet

Komboglyze 2.5 mg/1,000 mg film-coated tablets

saxagliptin/metformin hydrochloride
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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 pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What Komboglyze is and what it is used for

This medicine contains two different active substances called:
saxagliptin, belonging to a class of medicines known as DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors),
and
metformin, belonging to a class of medicines known as biguanides.
Both belong to a group of medicines called oral antidiabetics.

What Komboglyze is used for
This medicine is used to treat a type of diabetes called 'type 2 diabetes'.

How Komboglyze works
Saxagliptin and metformin work together to control blood sugar levels.
They increase insulin levels after meals and reduce the amount of sugar produced by the body.
Together with diet and physical exercise, this medicine helps lower blood sugar levels.
This medicine may be used alone or in combination with other antidiabetic medicines, including insulin.

To control diabetes, it is essential to follow a diet and engage in physical exercise, even while taking this medicine.
Therefore, it is important that you continue to follow your doctor’s or nurse’s advice regarding diet and physical activity.

2. What you should know before taking Komboglyze

Do not take Komboglyze:

• If you are allergic to saxagliptin, metformin, or any of the other ingredients of this medicine (listed in Section 6).
• If you have ever had a severe allergic reaction (hypersensitivity) to any other similar medicine you take to control your blood sugar levels. Symptoms of a severe allergic reaction may include:
  • Skin rashes.
  • Red spots or hives on the skin (urticaria).
  • Swelling of the face, lips, tongue, and throat, which may cause difficulty breathing or swallowing. If you experience these symptoms, stop taking this medicine immediately and contact your doctor or nurse without delay.
• If you have ever had a diabetic coma.
• If you have uncontrolled diabetes associated, for example, with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see below “Risk of lactic acidosis”) or ketoacidosis. Ketoacidosis is a condition in which substances called “ketone bodies” accumulate in the blood and may lead to diabetic pre-coma. Symptoms include stomach pain, rapid deep breathing, drowsiness, and breath with an unusual fruity odour.
• If you have severely reduced kidney function or liver problems.
• If you have recently had a heart attack or heart failure, or have serious circulatory problems or breathing difficulties that could indicate heart problems.
• If you have a severe infection or are dehydrated (your body has lost a lot of water).
• If you are breastfeeding (see also “Pregnancy and breastfeeding”).
• If you drink alcohol excessively (either daily or occasionally) (please see the section “Komboglyze and alcohol”).

Do not take this medicine if you have any of the conditions listed above. If you are unsure, speak with your doctor or pharmacist before taking this medicine.

Warnings and precautions

Risk of lactic acidosis

Komboglyze may cause a very rare but serious side effect called lactic acidosis, particularly if your kidneys are not functioning properly. The risk of developing lactic acidosis is higher in the presence of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see below for further information), liver problems, or any other medical condition characterised by reduced oxygen supply to part of the body (such as severe heart disease).

If you have any of the medical conditions described above, consult your doctor for further advice.

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

If you experience any of the symptoms of lactic acidosis, stop taking Komboglyze immediately and seek urgent medical attention at your nearest hospital, as lactic acidosis can lead to coma. Symptoms of lactic acidosis include:

• Vomiting
• Stomach ache (abdominal pain)
• Muscle cramps
• A general feeling of being unwell accompanied by severe tiredness
• Difficulty breathing
• Low body temperature and slower heart rate

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

Consult your doctor or pharmacist before taking Komboglyze:

• If you have type 1 diabetes (your body does not produce insulin). This medicine should not be used to treat this condition.
• If you have or have had a disease of the pancreas.
• If you are taking insulin or an antidiabetic medicine known as a “sulphonylurea”, your doctor may consider it necessary to reduce the dose of insulin or sulphonylurea when taken together with this medicine, in order to avoid low blood sugar levels.
• If you have had allergic reactions to any other medicine taken to control blood sugar levels.
• If you have a disease or are taking medicines that may lower your body’s defences against infections.
• If you have ever had heart failure or have other risk factors for developing heart failure, such as kidney problems. Your doctor will inform you about the signs and symptoms of heart failure. Contact your doctor, pharmacist, or nurse immediately if you notice any of these symptoms. Symptoms may include, but are not limited to, increasing shortness of breath, rapid weight gain, and swelling of the feet (pedal oedema).

If you are scheduled for major surgery, you must stop taking Komboglyze during the procedure and for a certain period afterwards. Your doctor will decide when you should stop and when you should restart treatment with Komboglyze.

Skin lesions are a common complication of diabetes. Skin rash has been observed with saxagliptin and with some antidiabetic medicines in the same class as saxagliptin. Follow the recommendations given to you by your doctor or nurse regarding skin and foot care. Contact your doctor if blisters appear on your skin, as this could be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop taking Komboglyze.

If you have any of the conditions listed above, or if you have any doubts, speak with your doctor or pharmacist before taking this medicine.

Tests or checks on kidney function

During treatment with Komboglyze, 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 worsens.

Children and adolescents

This medicine is not indicated for use in children and adolescents under 18 years of age. It is not known whether this medicine is safe and effective in children and adolescents under 18 years of age.

Other medicines and Komboglyze

If you are due to receive an injection of iodinated contrast medium into the bloodstream, for example during an X-ray procedure, you must stop taking Komboglyze before or during the injection. Your doctor will decide when you should stop and when you should restart treatment with Komboglyze.

Inform your doctor if you are taking, have recently taken, or might take any other medicines. You may need to monitor your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of Komboglyze. It is particularly important to mention the following:

• Cimetidine, a medicine used to treat stomach problems.
• Ketoconazole, used to treat fungal infections.
• Bronchodilators (beta-2 agonists), used to treat asthma.
• Diltiazem, used for high blood pressure.
• Rifampicin, an antibiotic used to treat infections such as tuberculosis.
• Corticosteroids, used to treat inflammatory diseases such as asthma and arthritis.
• Carbamazepine, phenobarbital, or phenytoin, used to control seizures (epileptic fits) or chronic pain.
• Medicines that increase urine production (diuretics).
• Medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib).
• Some medicines used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).

If you are taking any of the medicines listed above, or if you have any doubts, speak with your doctor or pharmacist before taking this medicine.

Komboglyze and alcohol

Avoid excessive alcohol consumption during treatment with Komboglyze, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”).

Pregnancy and breastfeeding

Do not take this medicine if you are pregnant or planning to become pregnant, as the medicine may affect the unborn child.

Do not take this medicine if you are breastfeeding or think you may need to breastfeed, as metformin passes into breast milk in small amounts.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Saxagliptin and metformin have negligible influence on the ability to drive or use machines. However, hypoglycaemia may affect your ability to drive and operate machinery, and there is a risk of hypoglycaemia when taking this medicine in combination with medicines known to cause hypoglycaemia, such as insulin and sulphonylureas.

3. How to take Komboglyze

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
If your doctor has prescribed this medicine together with a sulphonylurea or insulin, remember to take that other medicine exactly as directed by your doctor to achieve the best results for your health.

How much to take

• The dose of this medicine you should take depends on your condition and the doses of metformin and/or saxagliptin and metformin single tablets you are already taking. Your doctor will tell you the exact dose of this medicine to take.
• The recommended dose is one tablet twice daily. If you have reduced kidney function, your doctor may prescribe a lower dose.

How to take this medicine

• Take this medicine by mouth.
• Take it with meals to reduce the likelihood of stomach upset.

Diet and exercise
To control diabetes, it is necessary to follow a diet and engage in physical activity, even while taking this medicine. Therefore, it is important to continue following your doctor’s or nurse’s advice regarding diet and exercise. In particular, if you are following a low-calorie diet to control your weight, continue it during treatment with this medicine.

If you take more Komboglyze than you should
If you take more Komboglyze tablets than prescribed, contact your doctor immediately or go to hospital. Take the medicine with you.

If you forget to take Komboglyze

• If you forget to take a dose of this medicine, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take the next dose at the scheduled time.
• Do not take a double dose of this medicine to make up for a forgotten dose.

If you stop taking Komboglyze
Continue taking this medicine for as long as your doctor tells you to. This helps keep your blood sugar level under control.
If you have any doubts about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking this medicine and contact your doctor immediately if you experience any of the
following serious side effects:

• Lactic acidosis: Komboglyze may cause a very rare (may affect up to 1 in 10,000 people) but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking Komboglyze and seek immediate medical attention at the nearest doctor or hospital, because lactic acidosis can lead to coma.
• Severe and persistent abdominal pain (in the stomach area), possibly radiating to the back, as well as nausea and vomiting, as these may be signs of an inflamed pancreas (pancreatitis).

Contact your doctor if you experience any of the following side effects:

• Severe joint pain

Other side effects of Komboglyze include:
Common (may affect up to 1 in 10 people)

• headache
• muscle pain (myalgia)
• feeling unwell or indigestion (dyspepsia)
• urinary tract infection
• upper respiratory tract infection
• inflammation of the nose or throat, such as cold symptoms or sore throat
• inflammation of the stomach (gastritis) or intestine, sometimes due to infection (gastroenteritis)
• sinus infection, sometimes with pain and heaviness behind the cheeks and eyes (sinusitis)
• flatulence
• dizziness
• tiredness (fatigue)

Uncommon (may affect up to 1 in 100 people)

• joint pain (arthralgia)
• difficulty achieving or maintaining an erection (erectile dysfunction)

Side effects during treatment with saxagliptin alone:
Common

• dizziness
• tiredness (fatigue)

Side effects during treatment with saxagliptin alone or in combination:
Not known (frequency cannot be estimated from the available data)

• constipation
• blisters on the skin (bullous pemphigoid)

Some patients experienced a slight decrease in the number of a certain type of white blood cells (lymphocytes), detected by blood tests when saxagliptin was used alone or in combination. In addition, some patients reported skin rash and skin reactions (hypersensitivity) while taking saxagliptin.
During post-marketing use of saxagliptin, additional adverse events have been reported, including severe allergic reactions (anaphylaxis), and swelling of the face, lips, tongue, and throat, which may cause difficulty breathing or swallowing. If you have an allergic reaction, stop taking this medicine and contact your doctor immediately. Your doctor may prescribe a medicine to treat the allergic reaction and a different medicine for your diabetes.

Side effects during treatment with metformin alone:
Very common (may affect more than 1 in 10 people)

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

Common

• metallic taste in the mouth
• reduced or low levels of vitamin B12 in the blood: symptoms may include extreme tiredness (fatigue), sore and red tongue (glossitis), tingling sensations (paraesthesia), or pale or yellowish skin. Your doctor may prescribe certain tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other unrelated health problems.

Very rare

• liver problems (hepatitis)
• skin redness (rash) or itching

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system referred to in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Komboglyze

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and packaging following
EXP/Exp. The expiry date refers to the last day of that month.
Store below 25°C.
Do not use this medicine if you notice that the packaging is damaged or shows any signs of tampering.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Komboglyze contains
The active substances are saxagliptin and metformin hydrochloride.
Each film-coated tablet contains 2.5 mg of saxagliptin (as hydrochloride) and 1,000 mg of
metformin hydrochloride.
The other components (excipients) are:

• Tablet core: povidone K30, magnesium stearate.
• Film coating: polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc (E553b), yellow iron oxide (E172).
• Printing ink: shellac, indigo carmine aluminum lake (E132).

Description of the appearance of Komboglyze and package contents

• Komboglyze 2.5 mg/1,000 mg film-coated tablets (tablets) are pale yellow to light yellow, oval-shaped tablets, with "2.5/1000" printed on one side and "4247" on the other side in blue ink.
• Komboglyze is available in non-perforated aluminum blisters. Pack sizes contain 14, 28, 56 and 60 film-coated tablets in non-perforated blisters, multiple packs containing 112 (2 packs of 56) and 196 (7 packs of 28) film-coated tablets in non-perforated blisters, and 60x1 film-coated tablets in single-dose perforated blisters.

Not all pack 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
AstraZeneca UK Limited
Silk Road Business Park
Macclesfield
Cheshire
SK10 2NA
United Kingdom
For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:
België/Belgique/Belgien Lietuva
AstraZeneca S.A./N.V. UAB AstraZeneca Lietuva
Tel: +32 2 370 48 11 Tel: +370 5 2660550
България Luxembourg/Luxemburg
АстраЗенека България ЕООД AstraZeneca S.A./N.V.
Тел.: +359 (2) 44 55 000 Tél/Tel: +32 2 370 48 11
Česká republika Magyarország
AstraZeneca Czech Republic s.r.o. AstraZeneca Kft.
Tel: +420 222 807 111 Tel.: +36 1 883 6500
Danmark Malta
AstraZeneca A/S Associated Drug Co. Ltd
Tlf: +45 43 66 64 62 Tel: +356 2277 8000
Deutschland Nederland
AstraZeneca GmbH AstraZeneca BV
Tel: +49 40 809034100 Tel: +31 85 808 9900
Eesti Norge
AstraZeneca AstraZeneca AS
Tel: +372 6549 600 Tlf: +47 21 00 64 00
Ελλάδα Österreich
AstraZeneca A.E. AstraZeneca Österreich GmbH
Τηλ: +30 2 106871500 Tel: +43 1 711 31 0
España Polska
AstraZeneca Farmacéutica Spain, S.A. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +34 91 301 91 00 Tel.: +48 22 245 73 00
France Portugal
AstraZeneca AstraZeneca Produtos Farmacêuticos, Lda.
Tél: +33 1 41 29 40 00 Tel: +351 21 434 61 00
Hrvatska România
AstraZeneca d.o.o. AstraZeneca Pharma SRL
Tel: +385 1 4628 000 Tel: +40 21 317 60 41
Ireland Slovenija
AstraZeneca Pharmaceuticals (Ireland) DAC AstraZeneca UK Limited
Tel: +353 1609 7100 Tel: +386 1 51 35 600
Ísland Slovenská republika
Vistor hf. AstraZeneca AB, o.z.
Sími: +354 535 7000 Tel: +421 2 5737 7777
Italia Suomi/Finland
AstraZeneca S.p.A. AstraZeneca Oy
Tel: +39 02 00704500 Puh/Tel: +358 10 23 010
Κύπρος Sverige
Αλέκτωρ Φαρµακευτική Λτδ AstraZeneca AB
Τηλ: +357 22490305 Tel: +46 8 553 26 000
Latvija United Kingdom (Northern Ireland)
SIA AstraZeneca Latvija AstraZeneca UK Ltd
Tel: +371 67377100 Tel: +44 1582 836 836
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu