METFORMINA PHARMA COMBIX 1000 mg FILM-COATED TABLETS

2. What you need to know before you take Metformin Pharma Combix

Do nottakeMetformin PharmaCombix

• if you are allergic (hypersensitive) to metformin or any of the other ingredients of this medicine (listed in section 6)

• if you have liver problems
• if you have severe kidney function impairment
• 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 a pre-diabetic coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness or an unusual fruity odor in your breath
• if you have lost a lot of water from your body (dehydration), for example due to prolonged or severe diarrhea, or if you have vomited several times in a row. Dehydration can trigger kidney problems, which can put you at risk of developing lactic acidosis (see "Warnings and precautions")
• if you have a severe infection, for example an infection that affects your lungs, bronchi, or kidneys. Severe infections can trigger kidney problems, which can put you at risk of developing lactic acidosis (see "Warnings and precautions")
• if you are receiving treatment for acute heart failure or if you have recently had a heart attack, if you have severe circulation problems (such as shock) or if you have difficulty breathing. This can lead to a lack of oxygenation in the tissues, which can put you at risk of developing lactic acidosis (see "Warnings and precautions" below)
• if you drink a lot of alcohol.

If any of the above applies to you, consult your doctor before starting to take this medicine.

Make sure to consult your doctor

• if you need an examination such as an X-ray or a scan that involves injecting a contrast medium into your blood that contains iodine
• if you need major surgery.

You should stop taking metformin for a certain period before and after the examination or surgery. Your doctor will decide if you need any other treatment during this time. It is important that you follow your doctor's instructions precisely.

Warnings and precautions

Risk of lactic acidosis

Metformin can cause a very rare but very serious side effect called lactic acidosis, especially if your kidneys do not work properly. The risk of developing lactic acidosis is also increased with uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see more information below), liver problems, and any medical disorder in which a part of the body has a reduced oxygen supply (such as acute and severe heart disease).

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

Consult your doctor immediately 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, myopathy, lactic acidosis, and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD).
• You present any of the following symptoms after starting treatment with metformin: seizure, cognitive impairment, difficulty with body movements, symptoms indicative of nerve damage (e.g., pain or numbness), migraine, and hearing loss.

Stop takingmetforminand contact a doctor or the nearest hospital immediately if you experience any of the symptoms that produce lactic acidosis, as this disorder can lead to a coma.

The symptoms of lactic acidosis include:

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

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

Stop taking metformin for a short period if you have a disorder 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.

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

Metformin alone does not cause hypoglycemia (a blood sugar concentration that is too low). However, if you take metformin with other diabetes medicines that can cause hypoglycemia (such as sulfonylureas, insulin, meglitinides), there is a risk of hypoglycemia. If you experience symptoms of hypoglycemia, such as weakness, dizziness, increased sweating, increased heart rate, vision disorders, or difficulty concentrating, it is usually helpful to eat or drink something that contains sugar.

During treatment with metformin, your doctor will check your kidney function regularly, at least once a year, or more frequently if you are an elderly person and/or if your kidney function is deteriorating.

Other medicines andMetformin PharmaCombix

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

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

• 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 to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)
• beta-2 agonists, such as salbutamol or terbutaline (used to treat asthma)
• corticosteroids (used to treat various conditions, such as severe skin inflammation or asthma)
• medicines that may alter the amount of metformin in your blood, especially if you have reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib)
• other medicines used to treat diabetes.

TakingMetformin PharmaCombix with alcohol

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

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor, as changes may be needed in your treatment or your blood glucose levels may need to be monitored.

It is not recommended to take this medicine if you are breastfeeding or plan to breastfeed your baby.

Driving and using machines

Metformin alone does not cause hypoglycemia (a blood sugar concentration that is too low). This means it will not affect your ability to drive or use machines.

However, be careful if you take metformin with other diabetes medicines that can cause hypoglycemia (such as sulfonylureas, insulin, meglitinides). The symptoms of hypoglycemia include weakness, dizziness, increased sweating, increased heart rate, vision disorders, or difficulty concentrating. Do not drive or use machines if you start to feel these symptoms.

3. How to take Metformin Pharma Combix

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Metformin cannot replace the benefits of a healthy lifestyle. Continue to follow any dietary advice your doctor has given you and exercise regularly.

Recommended dose

Children aged 10 years and older, and adolescents

They usually start with 500 mg or 850 mg of metformin once a day. The maximum daily dose is 2,000 mg divided into 2 or 3 doses. Treatment of children between 10 and 12 years is only recommended under specific advice from your doctor, as clinical experience in this patient group is limited.

Adults

They usually start with 500 mg or 850 mg of metformin, 2 or 3 times a day. The maximum daily dose is 3,000 mg divided into 3 doses.

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

If you are also given insulin, your doctor will tell you how to start taking metformin.

Monitoring

• Your doctor will regularly perform blood glucose tests and adjust your metformin dose according to your blood glucose levels. Make sure to talk to your doctor regularly. This is particularly important for children, adolescents, or if you are an elderly person.
• Your doctor will also check how well your kidneys are working, at least once a year, or more frequently if you are an elderly person or if your kidneys are not working normally.

How to take Metformin Pharma Combix

Take metformin with meals or after meals. This will prevent you from suffering from side effects that affect your digestion. Do not chew or crush the tablets. Swallow each tablet with a glass of water.

• If you take one dose a day, take it in the morning (at breakfast).
• If you take two doses a day, take them in the morning (at breakfast) and at night (at dinner).
• If you take three doses a day, take them in the morning (at breakfast), at noon (at lunch), and at night (at dinner).

If, after some time, you think the effect of metformin is too strong or too weak, consult your doctor or pharmacist.

If you take more Metformina Pharma Combix than you should

If you have taken more metformin than you should, you may suffer from lactic acidosis. The symptoms of lactic acidosis are non-specific, such as vomiting, stomach pain (abdominal pain) with muscle cramps, a general feeling of discomfort with intense fatigue, and difficulty breathing. Additional symptoms may include a decrease in body temperature and heart rate. If you experience any of these symptoms, you should seek medical attention immediately, as lactic acidosis can lead to a coma. Stop takingmetforminimmediately and contact your doctor or the nearest hospital as soon as possible.

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Metformina Pharma Combix

Do not take a double dose to make up for forgotten doses. Take the next dose at the usual time.

If you have any further questions on the use of 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. The following side effects may occur:

Metformin can cause a very rare but very serious side effect called lactic acidosis (see section "Warnings and precautions"). If this happens to you, you should stop taking metformin and contact a doctor or the nearest hospital immediately, as lactic acidosis can lead to a coma.

Very common side effects (may affect more than 1 in 10 people):

• digestive problems, such as nausea, vomiting, diarrhea, stomach pain (abdominal pain), and loss of appetite. These side effects occur more frequently at the start of treatment with metformin. Spreading the doses throughout the day and taking metformin with food or immediately after a meal can help reduce these side effects. If the symptoms persist, stop taking metformin and consult your doctor.

Common side effects (may affect up to 1 in 10 people):

• changes in taste
• low or decreased vitamin B12 levels in the blood (symptoms may include extreme fatigue, red and painful tongue, numbness or tingling, or pale or yellowish skin). Your doctor may schedule some tests to find the reason for your symptoms because some of them may be caused by diabetes or other unrelated health problems.

Very rare side effects (may affect up to 1 in 10,000 people):

• lactic acidosis. It is a very rare but serious complication, especially if your kidneys do not work properly. The symptoms of lactic acidosis are non-specific (see section "Warnings and precautions")
• abnormalities in liver function tests or hepatitis (inflammation of the liver; this can cause fatigue, loss of appetite, weight loss, with or without a yellowish tint to the skin or the whites of the eyes). If this happens to you, stop takingmetforminand talk to your doctor
• skin reactions such as skin redness (erythema), itching, or an itchy rash (urticaria).

Children and adolescents

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Metformin Pharma Combix

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

If a child is being treated with metformin, it is advised that parents and caregivers supervise how this medicine is used.

No special storage conditions are required.

Do not use this medicine after the expiry date which is stated on the carton and blister after "EXP". The expiry date is the last day of the month shown.

Medicines should not be disposed of via wastewater or household waste. Place the carton and any remaining medicine in the SIGRE collection point at your pharmacy. Ask your pharmacist how to dispose of the carton and any remaining medicine. This will help protect the environment.

6. Container Content and Additional Information

Composition ofMetformin PharmaCombix 1,000 mg

• The active ingredient is metformin hydrochloride. One film-coated tablet of Metformin Pharma Combix 1,000 mg contains 1,000 mg of metformin hydrochloride, equivalent to 780 mg of metformin base.
• The other components are: povidone, magnesium stearate, hypromellose, and macrogol.

Appearance of the Product and Container Content

Film-coated tablets.

Metformin Pharma Combix 1,000 mg film-coated tablets EFG are white to yellowish, biconvex, oval-shaped film-coated tablets with the inscription MC on one side and a functional score on the other. The tablet can be divided into equal doses.

Metformin Pharma Combix 1,000 mg is available in packages of 30, 50, or 60 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Combix Laboratories, S.L.U.

C/ Badajoz 2, Building 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Galenicum Health, S.L.

Avda. Cornellá 144, 7th-1st,

Lekla Building

Esplugues de Llobregat

08950 Barcelona

Spain

Or

SAG Manufacturing S.L.U.

Crta. N-I, Km 36,

San Agustín de Guadalix,

28750 Madrid

Spain

Date of the Last Revision of this Prospectus: 03/2025

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/