KOMBOGLYZE 2.5 mg/1000 mg FILM-COATED TABLETS

2. What you need to know before you take 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 had a severe allergic reaction (hypersensitivity) to any other medicine used to control blood sugar.

The symptoms of a severe allergic reaction can include:

• Rash.
• Red raised patches on the skin (hives).
• Swelling of the face, lips, tongue, and throat that may cause difficulty breathing or swallowing.

If you experience any of these symptoms, stop taking this medicine and contact your doctor or healthcare professional immediately.

• 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 where 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 impairment or liver problems.
• If you have recently had a heart attack or if you have heart failure or any serious blood circulation problems or breathing difficulties that may be signs of heart problems.
• If you have a severe infection or are dehydrated (have lost a large amount of body water).
• If you are breastfeeding (see section "Pregnancy and breastfeeding").
• If you drink large amounts of alcohol (every day or only occasionally) (see section "Komboglyze with alcohol").

Do not take this medicine if you are in any of the above situations. If you are unsure, consult 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, 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 the body has a reduced supply of oxygen (such as severe and acute heart diseases).

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

Stop taking Komboglyze 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 Komboglyze 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 coma.

The symptoms of lactic acidosis include:

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

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

Consult your doctor quickly to indicate how to proceed 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).
• You experience any of the following symptoms after starting treatment with metformin: seizure, cognitive impairment, difficulty with body movements, symptoms indicating nerve damage (e.g., pain or numbness), migraine, and hearing loss.

Consult your doctor or pharmacist before starting Komboglyze

• If you have type 1 diabetes (your body does not produce any insulin). This medicine should not be used to treat this disease.
• If you have or have had pancreatitis.
• If you are taking insulin or an antidiabetic medicine known as a “sulfonylurea”, your doctor may want to reduce your dose of insulin or sulfonylurea when you take either of them with this medicine, to avoid low blood sugar levels.
• If you have had allergic reactions to any other medicine you take to control blood sugar.
• If you have a condition or are taking a medicine that may reduce your body's defenses 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. You should contact your doctor, pharmacist, or nurse immediately if you experience any of these symptoms. The symptoms can include, but are not limited to, an increasing feeling of shortness of breath, rapid weight gain, and swelling of the feet (maleolar edema).

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

Diabetic skin lesions are a common complication of diabetes. Skin rash has been observed with saxagliptin and with certain antidiabetic medicines in the same class as saxagliptin. Follow the skin and foot care recommendations given by your doctor or healthcare professional. Contact your doctor if you find blisters on your skin, as it may be a sign of a disease called bullous pemphigoid. Your doctor may ask you to stop taking Komboglyze.

If you are in any of the above situations, or if you are unsure, consult your doctor or pharmacist before using this medicine.

Kidney tests

During treatment with Komboglyze, 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.

Children and adolescents

This medicine is not recommended for use in children and adolescents under 18 years of age. It is not known if this medicine is safe and effective when used in children and adolescents under 18 years of age.

Other medicines and Komboglyze

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 Komboglyze before the injection or at the time of the injection. Your doctor will decide when you should stop taking Komboglyze and when you can restart it.

Tell your doctor or pharmacist 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 Komboglyze. It is especially important to mention the following:

• cimetidine, a medicine used to treat stomach problems.
• ketoconazole, which is used to treat fungal infections.
• bronchodilators (beta-2 agonists) used to treat asthma.
• diltiazem, which is used for high blood pressure.
• rifampicin, an antibiotic used to treat infections such as tuberculosis.
• corticosteroids, which are used to treat inflammation in diseases such as asthma and arthritis.
• carbamazepine, phenobarbital, or phenytoin, which are used to control epileptic seizures (convulsions) 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).
• certain medicines used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).

If you are in any of the above situations, or if you are unsure, consult your doctor or pharmacist before using this medicine.

Taking Komboglyze with alcohol

Avoid excessive alcohol intake while taking Komboglyze, as this can increase the risk of lactic acidosis (see section “Warnings and precautions”).

Pregnancy and breastfeeding

Do not take this medicine if you are pregnant or may become pregnant, as it may affect your baby.

Do not take this medicine if you are breastfeeding or plan to breastfeed. This is because metformin passes into human breast milk in small amounts.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

Saxagliptin and metformin have a negligible effect on the ability to drive and use machines. Hypoglycemia can affect your ability to drive and use machines or work with a firm support, and there is a risk of hypoglycemia when taking this medicine in combination with medicines with a known hypoglycemic effect, such as insulin or sulfonylureas.

3. How to take Komboglyze

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

If your doctor prescribes this medicine along with a sulfonylurea or insulin, remember to take this other medicine as your doctor has indicated to achieve the best results for your health.

How much to take

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

If you have reduced kidney function, your doctor may prescribe a lower dose.

How to take this medicine

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

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 follow the dietary and exercise recommendations given by your doctor or healthcare professional. In particular, if you are following a weight-control diet for diabetics, continue it while taking this medicine.

If you take more Komboglyze than you should

If you take more Komboglyze tablets than you should, talk to your doctor or go to the hospital immediately. Take the medicine pack 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 already time for your next dose, skip the missed dose and take the next dose at the usual time.
• Do not take a double dose of this medicine to make up for missed doses.

If you stop taking Komboglyze

Continue taking this medicine until your doctor tells you to stop. This will help you keep your blood sugar under control.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Stop taking this medicine and contact your doctor immediately if you notice any of the following serious adverse effects:

• Lactic Acidosis, Komboglyze can cause a very rare (may affect up to 1 in 10,000 people), but very serious, adverse effect called lactic acidosis (see section "Warnings and Precautions"). If this happens to you, you must stop taking Komboglyze and contact a doctor or the nearest hospital immediately, as lactic acidosis can lead to coma.
• Severe and Persistent Abdominal Pain(in the stomach area) that can reach the back, as well as nausea and vomiting, which could be a sign of having an inflamed pancreas (pancreatitis).

You should contact your doctor if you experience the following adverse effect:

• Severe Joint Pain

Other Adverse Effects of Komboglyze are:

Frequent (may affect up to 1 in 10 people)

• headache
• muscle pain (myalgia)
• nausea or indigestion (dyspepsia)
• infection of the urine transport structures (urinary tract infection)
• infection of the upper respiratory tract
• inflammation of the nose or throat like a cold or sore throat
• inflammation of the stomach (gastritis) or intestine, sometimes caused by an infection (gastroenteritis)
• infection of the sinuses, sometimes with a feeling of pain and pressure behind the cheekbones and eyes (sinusitis)
• flatulence
• dizziness
• fatigue (fatigue)

Infrequent (may affect up to 1 in 100 people)

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

Adverse Effects Observed During Treatment with Saxagliptin Alone:

Frequent

• dizziness
• fatigue (fatigue)

Adverse Effects Observed During Treatment with Saxagliptin Alone or in Combination:

Unknown (frequency cannot be estimated from available data):

• constipation
• appearance of blisters on the skin (bullous pemphigoid)

Some patients have presented a small reduction in the number of a type of white blood cell (lymphocytes) detected by blood tests while taking saxagliptin alone or in combination. Some patients have also presented eruptions and skin reactions (hypersensitivity) during treatment with saxagliptin.

During the post-authorization use of saxagliptin, additional adverse effects have been reported, including severe allergic reactions (anaphylaxis), and swelling of the face, lips, tongue, and throat that can cause difficulty breathing or swallowing. If you experience an allergic reaction, stop taking this medicine and contact your doctor immediately. Your doctor may prescribe a medicine to treat your allergic reaction and a different medicine for your diabetes.

Adverse Effects Observed During Treatment with Metformin Alone:

Very Frequent (may affect more than 1 in 10 people)

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

Frequent

• metallic taste in the mouth.
• low or decreased vitamin B12 blood levels (symptoms may include extreme fatigue (fatigue), red and painful tongue (glossitis), tingling (paresthesia) 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 unrelated health problems.

Very Rare

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

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 is not listed in this prospectus. 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. Conservation of Komboglyze

Keep this medicine out of sight and reach of children.

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

Store below 25°C.

Do not use this medicine if the packaging shows visible signs of deterioration or tampering.

Medicines should not be thrown away through drains or waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Komboglyze

The active ingredients 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.
• Coating film: polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc (E553b), yellow iron oxide (E172).
• Printing ink: shellac, aluminum carmine lake (E132).

Appearance of the Product and Package Contents

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

It is possible that in your country, only some package sizes are marketed.

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

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

Date of the Last Revision of this Prospectus:

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