Leaflet: information for the user

Metformin COMBIX 850 mg film-coated tablets EFG

Metformin hydrochloride

Read this leaflet carefully before you start taking the medicine.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others even if their symptoms are the same. It may harm them.
• If you think you have suffered a side effect, you can report it directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects, you can help provide more information on the safety of this medicine.

1. What isMetformin COMBIXand what is it used for

2. What you need to know before you take Metformin COMBIX

3. How to takeMetformin COMBIX

4. Possible side effects

5. Storage ofMetformin COMBIX

6. Further information

Metformina COMBIX is a medication for treating diabetes. It belongs to a group of medications called biguanides (a class of oral antidiabetic medications).

Insulin is a hormone produced by the pancreas that makes the body capture glucose (sugar) from the blood. The body uses glucose to produce energy or to store it for future use.

If you have type 2 diabetes, your pancreas does not produce enough insulin or your body cannot use the insulin it produces effectively. This causes a high concentration of glucose in the blood. Metformina COMBIX helps to reduce blood glucose to a normal concentration as possible.

If an overweight adult takes Metformina COMBIX for a prolonged period, it also helps to reduce the risk of complications associated with diabetes.

Metformina COMBIX is used to treat patients with type 2 diabetes (also known as "non-insulin-dependent diabetes") when diet and physical exercise alone have not been sufficient to control their blood glucose concentration. It is used especially in overweight patients.

Adults can take Metformina COMBIX alone or accompanied by other diabetes medications (oral medications or insulin).

Children aged 10 years and older, and adolescents, can take Metformina COMBIX alone or accompanied by insulin.

Do not take Metformina COMBIX

• if you are allergic (hypersensitive) to metformin or to any of the other components of Metformina COMBIX.
• if you have liver problems.
• if you have a severe reduction in kidney function;
• 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 disorder in which substances called "ketone bodies" accumulate in the blood, which can lead to diabetic precoma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or if your breath develops an unusual fruity odor.
• if you have lost too much water from your body (dehydration), for example due to prolonged or intense diarrhea, or if you have vomited several times in a row. Dehydration can trigger kidney problems, which can put you at risk of developing lactic acidosis (see below "Be careful with Metformina COMBIX").
• if you have a severe infection, for example a lung, bronchial, or kidney infection. Severe infections can trigger kidney problems, which can put you at risk of developing lactic acidosis (see below "Be careful with Metformina COMBIX").
• if you are receiving treatment for heart failure or have recently had a heart attack, if you have severe circulation problems or if you have difficulty breathing. This can make it difficult to supply oxygen to tissues, which can put you at risk of developing lactic acidosis (see below "Be careful with Metformina COMBIX").
• if you drink a large amount of alcohol.
• if you are breastfeeding.

If any of these circumstances apply to you, consult your doctor before starting to take this medication.

Make sure to consult your doctor if:

• You need an examination such as an X-ray or a scan that involves the injection of a contrast medium containing iodine into your bloodstream.
• You need a major surgical intervention.

You should stop taking Metformina COMBIX for a certain period before and after the examination or surgical intervention. Your doctor will decide on alternative treatment during this time. It is essential that you follow your doctor's instructions precisely.

Warnings and precautions

Risk of lactic acidosis

Metformina Combix 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 with uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see below "Be careful with Metformina COMBIX"), liver problems, and any medical condition in which a part of the body has a reduced oxygen supply (such as acute and severe heart disease).

Consult your doctor for further instructions if any of the above applies to you.

Consult your doctor immediately to determine how to proceed if:

• You know you have a genetic disorder that affects the mitochondria (the components that produce energy inside cells), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes) or maternal diabetes and hearing loss (MIDD).
• You experience any of the following symptoms after starting treatment with metformin: convulsions, cognitive impairment, difficulty with motor movements, symptoms indicative of nerve damage (e.g., pain or numbness), migraine, and hearing loss.

Stop taking Metformina COMBIX for a short period if you have a condition that may be associated with dehydration(significant loss of body fluids), such as intense vomiting, diarrhea, fever, exposure to heat, or if you drink less than normal. Consult your doctor for further instructions.

Stop taking Metformina COMBIX and contact a doctor or the nearest hospital immediately if you experience any of the symptoms that cause lactic acidosis,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
• reduced body temperature and heart rate

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

If you need to undergo major surgery, you should stop taking Metformina COMBIX while the procedure is being performed and for a period after it. Your doctor will decide when to interrupt treatment with Metformina COMBIX and when to resume it.

Metformin alone does not cause hypoglycemia (low blood sugar). However, if you take metformin with other diabetes medications that can cause hypoglycemia symptoms, such as weakness, dizziness, increased sweating, increased heart rate, visual disturbances, or difficulty concentrating, it is usually helpful to eat or drink something containing sugar.

During treatment with Metformina COMBIX, 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 deteriorating.

Other medications and Metformina COMBIX

If you need to receive an injection of a contrast medium containing iodine into your bloodstream, for example, in the context of an X-ray or examination, you should stop taking Metformina Combix before the injection or at the time of the injection. Your doctor will decide when to interrupt treatment with Metformina COMBIX and when to resume it.

Inform your doctor if you are taking, have taken recently, or may need to take any other medication. You may need more frequent blood glucose and kidney function tests, or your doctor may need to adjust the dose of Metformina COMBIX. It is especially important to mention the following:

• diuretics (medications that increase urine production)
• medications used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• certain medications used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)

• Corticosteroids (used to treat various conditions, such as severe skin inflammation or asthma)
• Beta-2 agonists such as salbutamol or terbutaline (used to treat asthma)

Taking Metformina COMBIX with alcohol

Avoid excessive alcohol consumption while taking Metformina COMBIX, as this can increase the risk of lactic acidosis (see "Warnings and precautions").

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medication.

During pregnancy, you need insulin to treat your diabetes. Inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant, so that your treatment can be changed.

Do not take this medication if you are breastfeeding or plan to breastfeed your baby.

Driving and operating machinery

Metformin alone does not cause hypoglycemia (low blood sugar). This means that it will not affect your ability to drive or operate machinery.

However, be careful if you take Metformina COMBIX with other diabetes medications that can cause hypoglycemia (such as sulfonylureas, insulin, or glinides). Hypoglycemia symptoms include weakness, dizziness, increased sweating, increased heart rate, visual disturbances, or difficulty concentrating. Do not drive or operate machinery if you start to feel these symptoms.

If you drive a vehicle or operate machinery, be aware of hypoglycemia symptoms (low blood sugar). Your concentration or reaction time may be reduced if you experience hypoglycemia. Never drive a vehicle or operate machinery if you think you are going to experience hypoglycemia. If you experience hypoglycemia frequently or find it difficult to recognize, consult your doctor to see if you can drive or operate machinery.

Additionally, visual disturbances due to possible hyperglycemia may also affect your ability to drive or operate machinery.

Follow exactly the administration instructions for Metformina COMBIX indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

Remember to take your medication.

Metformina COMBIX cannot replace the benefits of a healthy lifestyle. Continue following any dietary instructions given by your doctor and practice regular exercise.

Usual dose

Adults usually start with 500 mg or 850 mg of metformin, two or three times a day. The maximum daily dose is 3,000 mg divided into three doses.

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

The initial dose for children over 10 years old and adolescents is one tablet once a day, during or after meals. After 10-15 days of treatment, your doctor will adjust the dose. The maximum recommended dose in children is 2 g per day, divided into 2 or 3 doses. Treatment of children between 10 and 12 years old is only recommended under specific advice from your doctor, as clinical experience in this patient group is limited.

If you are also using insulin, your doctor will instruct you on how to start taking metformin.

Monitoring

Your doctor will instruct you to start treatment with a low dose of this medication and gradually increase it depending on the effects shown by blood tests.

How to take Metformina Combix

The tablets should be swallowed whole, without chewing and with a sufficient amount of liquid. When you have to take two or more tablets a day, you should take them separately, i.e., in the morning, at noon or at night.

If you estimate that the action of Metformina COMBIX is too strong or too weak, inform your doctor or pharmacist.

If you take more Metformina COMBIX than you should

If you have taken more metformin than you should, you may experience lactic acidosis. The symptoms of lactic acidosis are vomiting, abdominal pain with cramps, a feeling of discomfort with intense fatigue and difficulty breathing. Consult your doctor or pharmacist immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Metformina COMBIX

Do not take a double dose to compensate for the missed doses. Take the next dose at the usual time.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

If you interrupt treatment with Metformina Combix

If you interrupt treatment with metformin, your blood glucose levels may become uncontrolled, as well as the long-term effects of diabetes such as eye, kidney and vascular problems.

Like all medicines, Metformin COMBIX can cause side effects, although not everyone will experience them.

Metformin COMBIX can cause a very rare but serious side effect (may affect up to 1 in 10,000 people), called lactic acidosis (see "Warnings and precautions" section), If this happens to you,you should stop taking Metformin Combix and contact a doctor or the nearest hospital immediately,since lactic acidosis can lead to coma.

Very common (may affect more than 1 in 10 patients):

• Digestive problems such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These side effects occur more frequently when starting treatment. Help distribute the dose throughout the day and if you take the tablets during or immediately after a meal. If symptoms persist, discontinue treatment and consult your doctor.

Common (may affect between 1 and 10 in 100 patients):

• Changes in taste.

Rare (may affect fewer than 1 in 10,000 patients):

• Lactic acidosis. It is a rare but serious complication, especially if your kidneys do not function properly. The symptoms of lactic acidosis are nonspecific (see "Warnings and precautions" section).Skin reactions such as skin redness (erythema), itching, or itchy rash (urticaria).
• Low vitamin B12 levels in the blood.

Unknown frequency (cannot be estimated from available data):

• Abnormal liver function test results or hepatitis (inflammation of the liver: this can cause fatigue, loss of appetite, weight loss, with or without yellowing of the skin or the white of the eyes). If this happens to you, stop taking this medication.

Children and adolescents

Limited clinical data showed that side effects in children and adolescents were similar in nature and severity to those observed in adults.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

No special storage conditions are required.

Keep out of the reach and sight of children.

Expiration Date

Do not use Metformina COMBIX after the expiration date that appears on the packaging after “CAD”. The expiration date is the last day of the month indicated.

Do not dispose of medications through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Metformina COMBIX

• The active ingredient is hydrochloride of metformin. Each film-coated tablet contains 850 mg of hydrochloride of metformin.
• The other components are:

• Tablet core: hypromellose (E464), povidone, magnesium stearate.
• Tablet coating: hypromellose (E464), macrogol, titanium dioxide (E171).

Appearance of the product and contents of the package

Metformina COMBIX is presented in the form of film-coated tablets, white to off-white in color, round, biconvex, and smooth on both faces.

Metformina COMBIX is packaged in PVC/Aluminum blisters or white opaque high-density polyethylene bottles with a white opaque polypropylene cap with desiccant and is presented in packages of 50 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

LABORATORIOS COMBIX, S.L.U

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcon (Madrid), Spain

Responsible for manufacturing

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Pharmex Advanced Laboratories S.L.

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

This leaflet was approved in March 2025

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/