Estequen 50 mg/1,000 mg modified-release tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Estequen 50mg/1.000mg modified-release tablets

Estequen 100mg/1.000mg modified-release tablets

sitagliptin/metformin hydrochloride

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

• Keep this leaflet. 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 must not be given to other people, even if they have the same symptoms as you, because it could 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 Estequen is and what it is used for
2. What you need to know before taking Estequen
3. How to take Estequen
4. Possible side effects
5. How to store Estequen
6. Contents of the pack and other information

1. What Estequen is and what it is used for

Estequen 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. This medicine 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 produces 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) diseases, kidney (renal) diseases, blindness, and amputations.

2. What you need to know before taking Estequen

Do not take Estequen

• 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, 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 severe infection or are dehydrated
• if you are undergoing an X-ray procedure requiring injection of a contrast agent. You will need to stop taking this medicine at the time of the procedure and for 2 or more days afterwards, as directed by your doctor, depending on how well your kidneys are functioning
• if you recently had a heart attack or have serious circulatory problems, such as “shock” or difficulty breathing
• if you have liver problems
• if you drink alcohol excessively (either daily or occasionally)
• if you are breastfeeding.

Do not take this medicine 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 this medicine.

Warnings and precautions

Cases of inflammation of the pancreas (pancreatitis) have been reported in patients treated with this medicine (see section 4).

If you develop blisters on your skin, this may be a sign of a disease called bullous pemphigoid. Your doctor may ask you to stop taking this medicine.

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, severe infections, prolonged fasting, 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 diseases).

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

Temporarily stop taking sitagliptin/metformin if you develop a condition that may 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 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.

Contact your doctor promptly for guidance 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, difficulty with body movements, signs of nerve damage (e.g., pain or numbness), migraine, or hearing loss.

Consult your doctor or pharmacist before starting this medicine:

• if you have or have had a pancreatic disease (such as pancreatitis)

  • 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 condition may also be called insulin-dependent diabetes

• if you have had an allergic reaction to sitagliptin, metformin, or this medicine (see section 4)

• if you are taking a sulfonylurea or insulin, or other diabetes medicines at the same time, 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 must stop taking this medicine during the procedure and for a period afterwards. Your doctor will decide when to interrupt and when to restart treatment with this medicine.

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

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 declining.

Children and adolescents

Children and adolescents under 18 years of age must 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 when used in children under 10 years of age.

Other medicines and Estequen

If you need to receive an injection of an iodine-containing contrast agent into your bloodstream, 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 when to 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 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, by inhalation, or 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 taken with this medicine.

Taking Estequen with alcohol

Avoid excessive alcohol consumption while taking this medicine, 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 or pharmacist before using this medicine. You must not take this medicine during pregnancy or while breastfeeding. (See section 2, Do not take Estequen).

Driving and using machines

The effect of this medicine on the ability to drive and use machines is negligible or minor. 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 may affect your ability to drive and use machines or work without secure support.

Estequen contains sodium

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

3. How to take Estequen

Follow exactly the administration instructions for this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again. Your doctor will tell you how many tablets to take and when to take them.

The maximum daily dose is 100 mg of sitagliptin and 2,000 mg of metformin.

Usually, you should take the tablets once daily at dinner time.

In some cases, your doctor may recommend taking the tablets twice daily.

Take the tablets with food to reduce the likelihood of stomach discomfort.

Swallow the tablets whole with a glass of water; do not chew them.

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

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

You must continue the diet recommended by your doctor during treatment with this medicine and ensure that carbohydrate intake is evenly distributed throughout the day.

It is unlikely that treatment with this medicine alone will cause abnormally low blood sugar (hypoglycemia). However, 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 Estequen than you should

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”).

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

If you forget to take Estequen

If you forget to take a dose, take it as soon as you remember. If you only remember when it is time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose of this medicine to make up for a missed dose.

If you stop taking Estequen

Keep taking this medicine for as long as your doctor prescribes it, to help control your blood sugar levels. Do not stop taking this medicine without first consulting your doctor. If you stop treatment with this medicine, your blood sugar levels may rise again.

If you have any further questions about using this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences 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 radiate 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 this medicine 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: cannot be estimated from available data), including skin rash, hives, skin blistering or peeling, or swelling of the face, lips, tongue, or throat that may cause difficulty breathing or swallowing, stop taking this medicine and contact your doctor immediately. Your doctor will prescribe treatment for the allergic reaction and switch you to another medicine for the treatment of 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, 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 (classified as common).

Some patients 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 when taking this medicine in combination with pioglitazone:

Common: swelling of hands or legs

Some patients experienced the following adverse effects when 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 this medicine) 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, pain in the arm or leg
Uncommon: dizziness, constipation, itching
Rare: reduction in platelet count
Frequency not known: kidney problems (sometimes requiring 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, diarrhea, stomach pain, and loss of appetite. These symptoms may occur when you first start taking metformin and usually resolve over time
Common: metallic taste, low or decreased levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), red and painful tongue (glossitis), tingling (paresthesia), or pale or yellowish skin). Your doctor may arrange some tests to determine the cause of your symptoms, as some of these may also be caused by diabetes or other unrelated health conditions
Very rare: hepatitis (a liver problem), hives, skin redness (rash), or itching

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are possible adverse effects 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 Estequen

Keep this medicine out of sight and reach of children.

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

Do not store above 25°C.

Medicines must not be disposed of via wastewater or household waste. Unused medicines and their containers should be returned to the SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of any unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Estequen

• The active substances are sitagliptin and metformin.

Estequen 50 mg/1,000 mg: Each tablet contains sitagliptin monohydrochloride monohydrate equivalent to 50 mg of sitagliptin and 1,000 mg of metformin hydrochloride.

Estequen 100 mg/1,000 mg: Each tablet contains sitagliptin monohydrochloride monohydrate equivalent to 100 mg of sitagliptin and 1,000 mg of metformin hydrochloride.

• The other components are:

• Metformin extended-release layer: hypromellose, magnesium stearate.

• Sitagliptin immediate-release layer: calcium hydrogen phosphate, microcrystalline cellulose, sodium stearyl fumarate, sodium croscarmellose (see section 2, "Estequen contains sodium").

• In addition, the coating contains:

Estequen 50 mg/1,000 mg: poly(vinyl alcohol), titanium dioxide (E171), macrogol 4000, talc.

Estequen 100 mg/1,000 mg: partially hydrolysed poly(vinyl alcohol), titanium dioxide (E171), macrogol 4000, talc, yellow iron oxide (E172), red iron oxide (E172).

Appearance of the product and contents of the pack

Estequen 50 mg/1,000 mg are white, oval-shaped, biconvex tablets, 22.2 mm x 10.8 mm in size, marked with "50" on one side and "1000" on the other.

Estequen 100 mg/1,000 mg are orange, oval-shaped, biconvex tablets, 22.2 mm x 10.8 mm in size, marked with "100" on one side and "1000" on the other.

PVC/PVDC/aluminium blisters.

Pack sizes of 14, 28, 30, 56, 60, 98, 112, 180 and 200 modified-release tablets.

Only certain pack sizes may be commercially available.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Teva Pharma, S.L.U.
C/Anabel Segura, 11 Edificio Albatros B, 1st floor
Alcobendas 28108 Madrid
Spain

Manufacturer

Adamed Pharma S.A.
ul. Marszalka Józefa Pilsudskiego 5
95-200 Pabianice,
Poland

Merckle GmbH
Graf-Arco-Str. 3
89079 Ulm
Germany

Merckle GmbH
Ludwig-Merckle-Strasse 3
89143 Blaubeuren
Germany

Date of the most recent revision of this leaflet: April 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/)