SITAGLIPTIN/METFORMIN COMBIX 50mg/1000mg FILM-COATED TABLETS

2. What you need to know before you take Sitagliptin/Metformin Combix

Do not takeSitagliptin/Metformin Combix

• if you are allergic to sitagliptin, metformin, or any of the other ingredients of this medicine (listed in section 6)
• if you have severe kidney problems
• 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 in which substances called “ketone bodies” build up in the blood, which can lead to a pre-diabetic coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or unusual fruity odor of the breath
• if you have a severe infection or are dehydrated
• if you are going to have an X-ray where you will be injected with a contrast agent. You will need to stop taking sitagliptin/metformin at the time of the X-ray and for 2 or more days after, as directed by your doctor, depending on your kidney function
• if you have recently had a heart attack or have severe circulatory problems, such as “shock” or breathing difficulties
• if you have liver problems (hepatic problems)
• if you drink excessive amounts of alcohol (either every day or only occasionally)
• if you are breastfeeding.

Do not take sitagliptin/metformin if any of the above applies to you and consult your doctor about other ways to control your diabetes. If you are not sure, consult your doctor, pharmacist, or nurse before taking sitagliptin/metformin.

Warnings and precautions

There have been reports of pancreatitis (inflammation of the pancreas) in patients treated with sitagliptin/metformin (see section 4).

If you notice blisters on your skin, it may be a sign of a disease called bullous pemphigoid. Your doctor may ask you to stop taking sitagliptin/metformin.

Risk of lactic acidosis

Sitagliptin/metformin 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 below), liver problems, and any medical condition in which a part of the body has a reduced supply of oxygen (such as acute and severe heart problems).

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

Consult your doctor immediately if:

• You know you have a genetic disease that affects the mitochondria (the energy-producing components within cells), such as MELAS syndrome (mitochondrial encephalomyopathy, 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.

Stop taking sitagliptin/metformin 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 sitagliptin/metformin and contact a doctor or the nearest hospital immediately if you experience any of the symptoms of 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
• reduction in body temperature and heart rate

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

Consult your doctor or pharmacist before starting to take sitagliptin/metformin:

• if you have or have had pancreatitis (inflammation of the pancreas)
• if you have or have had gallstones, alcohol addiction, or very high blood levels of triglycerides (a type of fat). These medical conditions may increase your risk of developing pancreatitis (see section 4)
• if you have type 1 diabetes. This disease is also called insulin-dependent diabetes
• if you have had an allergic reaction to sitagliptin, metformin, or sitagliptin/metformin (see section 4)
• if you are taking a sulfonylurea or insulin, other diabetes medicines, as you may experience low blood sugar levels (hypoglycemia). Your doctor may consider reducing the dose of your sulfonylurea or insulin

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

If you are not sure if any of the above applies to you, consult your doctor or pharmacist before taking sitagliptin/metformin.

During treatment with sitagliptin/metformin, 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

Children and adolescents under 18 years should not use this medicine. It is not effective in children and adolescents aged 10 to 17 years. It is not known if this medicine is safe and effective when used in children under 10 years.

Other medicines and Sitagliptin/Metformin Combix

If you need to be given an injection of a contrast agent containing iodine into your bloodstream, for example, in the context of an X-ray or scan, you should stop taking sitagliptin/metformin before the injection or at the time of the injection. Your doctor will decide when you should stop taking sitagliptin/metformin 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 sitagliptin/metformin. It is especially important to mention the following:

• medicines (taken orally, inhaled, or injected) used to treat diseases that cause inflammation, such as asthma and arthritis (corticosteroids)
• 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)
• medicines used to treat bronchial asthma (beta-sympathomimetics)
• iodinated contrast agents or medicines that contain alcohol
• certain medicines used to treat stomach problems, such as cimetidine
• ranolazine, a medicine used to treat angina pectoris
• dolutegravir, a medicine used to treat HIV infection
• vandetanib, a medicine used to treat a specific type of thyroid cancer (medullary thyroid cancer)
• digoxin (for treating irregular heartbeat and other heart problems). Your doctor may need to check the level of digoxin in your blood if you are taking sitagliptin/metformin.

Taking Sitagliptin/Metformin Combix with alcohol

Avoid excessive alcohol intake while taking sitagliptin/metformin, 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 are planning to have a baby, ask your doctor for advice before taking this medicine. You should not take this medicine during pregnancy. You should not take this medicine if you are breastfeeding. See section 2, Do not takesitagliptin/metformin.

Driving and using machines

The effect of this medicine on your ability to drive or use machines is negligible or non-existent. However, there have been reports of dizziness and drowsiness during treatment with sitagliptin, which may affect your ability to drive or use machines.

Taking this medicine with sulfonylureas or insulin may cause low blood sugar levels (hypoglycemia), which may affect your ability to drive or use machines or work without a secure support.

Sitagliptin/Metformin Combix contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet, which is essentially “sodium-free”.

3. How to take Sitagliptin/Metformin Combix

Follow exactly the instructions for administration of this medicine given by your doctor.

In case of doubt, consult your doctor or pharmacist again.

• Take one tablet:

• twice a day by mouth
• with food to reduce the likelihood of stomach upset

• Your doctor may need to increase the dose to control your blood sugar levels.
• If you have reduced kidney function, your doctor may prescribe a lower dose.

You should continue with the diet recommended by your doctor during treatment with this medicine and be careful to distribute your carbohydrate intake evenly throughout the day.

It is unlikely that treatment with this medicine alone will cause you to have low blood sugar levels (hypoglycemia). Low blood sugar levels may occur when this medicine is taken with a medicine that contains a sulfonylurea or with insulin, so your doctor may consider reducing the dose of your sulfonylurea or insulin.

If you take more Sitagliptin/Metformin Combix than you should

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

If you take more than the prescribed dose of this medicine, contact your doctor immediately. Go to the hospital if you have symptoms of lactic acidosis such as feeling cold or unwell, nausea or severe vomiting, stomach pain, unexplained weight loss, muscle cramps, or rapid breathing (see section “Warnings and precautions”).

If you forget to take Sitagliptin/Metformin Combix

If you miss a dose, take it as soon as you remember. If you do not remember until the time of your next dose, skip the missed dose and continue with your regular treatment. Do not take a double dose of this medicine.

If you stop taking Sitagliptin/Metformin Combix

Keep taking this medicine for as long as your doctor recommends to help control your blood sugar levels. Do not stop taking this medicine without consulting your doctor first. If you stop taking sitagliptin/metformin, your blood sugar levels may increase again.

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 sitagliptin/metformin and go to the doctor immediately if you notice any of the following serious adverse effects:

• Severe and persistent abdominal pain (stomach area) that can reach the back with or without nausea and vomiting, as these can be signs of pancreatitis.

Sitagliptin/metformin may 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 sitagliptin/metformin and contact a doctor or the nearest hospital immediately, as lactic acidosis can lead to coma.

If you have a severe allergic reaction (frequency not known), including skin rash, hives, blisters on the skin/peeling of the skin, and swelling of the face, lips, tongue, and throat that can cause difficulty breathing or swallowing, stop taking this medicine and consult your doctor immediately. Your doctor will prescribe a medicine to treat the allergic reaction and change the medicine for the treatment of diabetes.

Some patients who took metformin have experienced the following adverse effects after starting treatment with sitagliptin:

Frequent (may affect up to 1 in 10 people): low blood sugar, nausea, gas, vomiting

Infrequent (may affect up to 1 in 100 people): stomach pain, diarrhea, constipation, drowsiness

Some patients have experienced diarrhea, nausea, gas, constipation, stomach pain, or vomiting when starting treatment with the combination of sitagliptin and metformin (frequency classified as frequent).

Some patients have experienced the following adverse effects when taking this medicine with a sulfonylurea such as glimepiride:

Very frequent (may affect more than 1 in 10 people): low blood sugar levels

Frequent: constipation

Some patients presented the following adverse effects while taking this medicine in combination with pioglitazone:

Frequent: swelling of hands or feet

Some patients presented the following adverse effects while taking this medicine in combination with insulin:

Very frequent: low blood sugar levels

Infrequent: dry mouth, headache

Some patients have experienced the following adverse effects during clinical trials while taking sitagliptin alone (one of the medicines that contains Sitagliptin/Metformin Combix) or during use after the approval of sitagliptin/metformin or sitagliptin alone or with other diabetes medicines:

Frequent: low blood sugar levels, headache, upper respiratory tract infection, congestion or nasal mucosity and sore throat, arthrosis, pain in the arm or leg

Infrequent: dizziness, constipation, itching

Rare: reduction of platelet count

Frequency not known: kidney problems (which may require dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of skin blister)

Some patients have experienced the following adverse effects after taking metformin alone:

Very frequent: nausea, vomiting, diarrhea, stomach pain, and loss of appetite. These symptoms may appear when you start taking metformin and usually disappear

Frequent: metallic taste, decrease or low levels of vitamin B12 in blood (symptoms may include extreme fatigue, pain and redness of the tongue, tingling, or pale or yellowish skin). Your doctor may ask you for some tests to determine the cause of your symptoms, as some of them may also be caused by diabetes or other unrelated health problems

Very rare: hepatitis (a liver problem), hives, skin redness (rash), or itching

Reporting of Adverse Effects

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

5. Conservation of Sitagliptin/Metformin Combix

Keep this medicine out of sight and reach of children.

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

Do not store at a temperature above 30 °C.

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and medicines you no longer need in the SIGRE Point of the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Content of the Package and Additional Information

Composition of Sitagliptin/Metformin Combix

• The active ingredients are sitagliptin and metformin.
• • Sitagliptin/Metformin Combix 50 mg/850 mg film-coated tablets EFG: each tablet contains 50 mg of sitagliptin (as hydrochloride) and 850 mg of metformin hydrochloride.
  • Sitagliptin/Metformin Combix 50 mg/1000 mg film-coated tablets EFG: each tablet contains 50 mg of sitagliptin (as hydrochloride) and 1000 mg of metformin hydrochloride.
• The other components are:

Core of the tablet: microcrystalline cellulose, povidone (K29/32), sodium lauryl sulfate, magnesium stearate.

Film coating (50 mg/850 mg): polyethylene glycol and polyvinyl alcohol copolymer grafted with polyethylene glycol (E1209), talc (E553b), titanium dioxide (E171), monoglycerides and diglycerides of fatty acids (E471), polyvinyl alcohol (E1203), and red iron oxide (E172)

Film coating (50 mg/1000 mg): polyethylene glycol and polyvinyl alcohol copolymer grafted with polyethylene glycol (E1209), talc (E553b), titanium dioxide (E171), red iron oxide (E172), monoglycerides and diglycerides of fatty acids (E471), polyvinyl alcohol (E1203), and black iron oxide (E172).

Appearance of the Product and Package Content

Sitagliptin/Metformin Combix 50 mg/850 mg film-coated tablets EFG: film-coated tablet, oval-shaped, biconvex, with approximate dimensions of 20.5 mm x 9.5 mm, pink in color, engraved with "S476" on one side and flat on the other.

Sitagliptin/Metformin Combix 50 mg/1000 mg film-coated tablets EFG: film-coated tablet, oval-shaped, biconvex, with approximate dimensions of 21.5 mm x 10.0 mm, brown in color, engraved with "S477" on one side and flat on the other.

Sitagliptin/Metformin Combix 50 mg/850 mg film-coated tablets EFG are presented in

• Blister pack composed of opaque PVC/PVDC-Aluminum

Packaging of 14, 28, 30, 56, 60, 196, and 210 tablets.

• HDPE white bottle with desiccant silica gel contained in the screw cap

Packaging of 100 and 196 tablets.

Sitagliptin/Metformin Combix 50 mg/1000 mg film-coated tablets EFG are presented in

• Blister pack composed of opaque PVC/PVDC-Aluminum

Packaging of 14, 28, 30, 56, 60, 196, and 210 tablets.

• HDPE white bottle with desiccant silica gel contained in the screw cap

Packaging of 100 and 196 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Laboratorios Liconsa S.A.

Avda. Miralcampo, nº 7, Polígono Industrial Miralcampo

19200 Azuqueca de Henares (Guadalajara)

Spain

Date of the Last Revision of this Prospectus: July 2025

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