Sitagliptin/metformin Combix 50 mg/1000 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Sitagliptina/Metformina Combix 50 mg/850 mg film-coated tablets EFG

Sitagliptina/Metformina Combix 50 mg/1000 mg film-coated tablets EFG

sitagliptin/metformin hydrochloride

Read this entire leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet as 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, and you should not give it to others, even if they have the same symptoms as you, since it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Sitagliptina/Metformina Combix is and what it is used for

Sitagliptina/Metformina Combix contains two different medicines called sitagliptin and metformin.

• Sitagliptin belongs to a class of medicines known as DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors).
• Metformin belongs to a class of medicines known as biguanides.

Together, they work to control blood sugar levels in adult patients with a form of diabetes called "type 2 diabetes mellitus." This medicine helps increase insulin levels produced after a meal and reduces the amount of sugar produced by your body.

Along with diet and exercise, this medicine helps lower your blood sugar level. It can be used alone or in combination with certain other diabetes medicines (insulin, sulfonylureas, or glitazones).

What is type 2 diabetes?

Type 2 diabetes is a condition in which your body does not produce enough insulin and the insulin your body does produce does not work as well as it should. Your body may also produce too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems, such as heart (cardiovascular) disease, kidney (renal) disease, blindness, and amputations.

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

Do not take Sitagliptin/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 severely reduced kidney function
• if you have uncontrolled diabetes with, for example, severe hyperglycemia (high blood glucose), 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” accumulate in the blood, which may lead to diabetic pre-coma. Symptoms include stomach pain, rapid deep breathing, drowsiness, or fruity-smelling breath
• if you have a serious infection or are dehydrated
• if you are scheduled for an X-ray requiring injection of a contrast agent. You will need to stop taking sitagliptin/metformin at the time of the scan and for 2 or more days afterwards, as directed by your doctor, depending on how well your kidneys are functioning
• if you have recently had a heart attack or have serious circulatory problems such as “shock” or difficulty breathing
• if you have liver problems (hepatic)
• if you drink alcohol excessively (either daily or occasionally)
• if you are breastfeeding.

Do not take sitagliptin/metformin if any of the above apply to you, and consult your doctor about other ways to manage your diabetes. If you are unsure, consult your doctor, pharmacist, or nurse before starting sitagliptin/metformin.

Warnings and precautions

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

If you develop blisters on the skin, this may be a sign of a condition 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 serious adverse effect called lactic acidosis, especially if your kidneys are not functioning properly. The risk of developing lactic acidosis is also increased in uncontrolled diabetes, serious infections, prolonged fasting or alcohol consumption, dehydration (see further information below), liver problems, and any medical condition in which part of the body has reduced oxygen supply (such as acute and serious heart conditions).

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

Contact your doctor immediately for advice if:

• You are known to have a genetic mitochondrial disorder (components that produce energy inside cells), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, 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: seizures, cognitive decline, movement difficulties, signs of nerve damage (e.g., pain or numbness), migraine, or deafness.

Stop taking sitagliptin/metformin temporarily if you develop a condition that could lead to dehydration (significant loss of body fluids), such as severe vomiting, diarrhea, fever, heat exposure, or if you are drinking less fluid than usual. Consult your doctor for further instructions.

Stop taking sitagliptin/metformin and contact a doctor or go to the nearest hospital immediately if you experience any symptoms of lactic acidosis, as this condition may lead to coma.

Symptoms of lactic acidosis include:

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• general feeling of discomfort with profound fatigue
• difficulty breathing
• decreased 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 sitagliptin/metformin if:

• you have or have had a pancreatic disease (such as pancreatitis)
• 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)
• you have type 1 diabetes. This condition may also be called insulin-dependent diabetes
• you have had or have a known allergic reaction to sitagliptin, metformin, or sitagliptin/metformin (see section 4)
• you are taking a sulfonylurea or insulin, or other diabetes medications together with sitagliptin/metformin, as you may experience low blood sugar levels (hypoglycemia). Your doctor may consider reducing the dose of your sulfonylurea or insulin

If you require major surgery, you should stop taking sitagliptin/metformin during the procedure and for a period afterwards. Your doctor will decide when to interrupt and restart treatment with sitagliptin/metformin.

If you are unsure whether any of the above conditions apply to you, consult your doctor or pharmacist before starting sitagliptin/metformin.

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

Children and adolescents

Children and adolescents under 18 years of age should not use this medicine. It is not effective in children and adolescents aged between 10 and 17 years. It is unknown whether this medicine is safe and effective in children under 10 years of age.

Other medicines and Sitagliptin/Metformin Combix

If you need to receive an intravenous injection of an iodine-containing contrast agent, for example during an X-ray or scan, you must stop taking sitagliptin/metformin before or at the time of the injection. Your doctor will decide when to interrupt and restart treatment with sitagliptin/metformin.

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. You may require 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, by inhalation, or by injection) used to treat inflammatory conditions 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)
• specific medicines for bronchial asthma (β-sympathomimetics)
• iodinated contrast agents or medicines containing 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 (to treat irregular heartbeat and other heart problems). Blood levels of digoxin may need to be monitored if you are taking sitagliptin/metformin.

Taking Sitagliptin/Metformin Combix with alcohol

Avoid excessive alcohol consumption 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 plan to become pregnant, consult your doctor before using 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 take sitagliptin/metformin.

Driving and using machines

The effect of this medicine on the ability to drive and use machines is negligible or none. However, dizziness and drowsiness have been reported during treatment with sitagliptin, which may affect your ability to drive and use machines.

Taking this medicine together with medicines called sulfonylureas or with insulin may cause hypoglycemia, which could impair your ability to drive and use machines or work without 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 administration instructions given by your doctor for this medicine.

If in doubt, consult your doctor or pharmacist again.

• Take one tablet:

• twice daily, orally

• with food to reduce the likelihood of stomach discomfort

• Your doctor may need to increase the dose to control blood sugar levels.

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

You must continue the diet recommended by your doctor during treatment with this medicine and take care to evenly distribute carbohydrate intake throughout the day.

It is unlikely that treatment with this medicine alone will cause abnormally low blood sugar (hypoglycemia). Low blood sugar may occur when this medicine is taken together with a medicine containing a sulfonylurea or with insulin, so your doctor may consider it necessary to reduce the dose of your sulfonylurea or insulin.

If you take more Sitagliptin/Metformin Combix than you should

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

If you take more than the prescribed dose of this medicine, contact your doctor immediately. Go to the hospital if you experience symptoms of lactic acidosis such as feeling cold or unwell, severe nausea or 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 forget to take 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 dosing schedule. 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 instructs, to help control your blood sugar levels. Do not stop taking this medicine without first consulting your doctor. If you stop treatment with sitagliptin/metformin, your blood sugar levels may rise again.

If you have any further questions about 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 everyone will experience them.

STOP taking sitagliptin/metformin and contact your doctor immediately if you experience any of the following serious adverse effects:

• Severe and persistent pain in the abdomen (stomach area), which may extend to the back, with or without nausea and vomiting, as these may be signs of inflammation of the pancreas (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 occurs, you must stop taking sitagliptin/metformin and contact a doctor or go to 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, skin blisters/skin peeling, and swelling of the face, lips, tongue, and throat that may cause difficulty breathing or swallowing, stop taking this medicine and consult your doctor immediately. Your doctor will prescribe a treatment for the allergic reaction and switch you to another medicine for diabetes.

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

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

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

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

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

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

Common: constipation

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

Common: swelling of hands or legs

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

Very common: low blood sugar levels

Uncommon: dry mouth, headache

Some patients experienced the following adverse effects during clinical studies while taking sitagliptin alone (one of the medicines contained in Sitagliptin/Metformin Combix) or during post-approval use of sitagliptin/metformin or sitagliptin alone or in combination with other diabetes medicines:

Common: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose, sore throat, osteoarthritis, arm or leg pain

Uncommon: dizziness, constipation, itching

Rare: reduction in the number of platelets

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

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

Very common: nausea, vomiting, diarrhoea, stomach pain, and loss of appetite. These symptoms may occur when you first start taking metformin and usually go away

Common: metallic taste, decreased or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling (paraesthesia), or pale or yellowish skin). Your doctor may request 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 adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Sitagliptin/Metformin Combix

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

Do not use this medicine after the expiry date stated on the blister or bottle and on the outer packaging after EXP. The expiry date refers to the last day of the month indicated.

Do not store above 30 °C.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE Point in your pharmacy. Ask your pharmacist how to properly dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Sitagliptin/Metformin Combix

• The active substances 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.
• Other components are:

Tablet core: microcrystalline cellulose, povidone (K29/32), sodium lauryl sulfate, magnesium stearate.

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

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

Nature and contents of the container

Sitagliptin/Metformin Combix 50 mg/850 mg film-coated tablets EFG: film-coated tablet, oval-shaped, biconvex, approximately 20.5 mm x 9.5 mm, pink in colour, marked with "S476" on one side and plain on the other.

Sitagliptin/Metformin Combix 50 mg/1000 mg film-coated tablets EFG: film-coated tablet, oval-shaped, biconvex, approximately 21.5 mm x 10.0 mm, brown in colour, marked with "S477" on one side and plain on the other.

Sitagliptin/Metformin Combix 50 mg/850 mg film-coated tablets EFG is available in:

• Blister composed of opaque PVC/PVDC-Aluminum

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

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

Packs of 100 and 196 tablets.

Sitagliptin/Metformin Combix 50 mg/1000 mg film-coated tablets EFG is available in:

• Blister composed of opaque PVC/PVDC-Aluminum

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

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

Packs of 100 and 196 tablets.

Only certain pack 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 most recent revision of this leaflet: July 2025

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