Patient Information Leaflet

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

Estequen 100mg/1,000mg modified-release tablets

sitagliptin/metformin hydrochloride

Read this leaflet carefully before you start taking this medicine, as 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, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section4.

1.What Estequen is and what it is used for

2.What you need to know before you start taking Estequen

3.How to take Estequen

4.Possible side effects

5.Storage of Estequen

6.Contents of the pack and additional information

Estequencontains two different medications, called sitagliptin and metformin.

• Sitagliptin belongs to a class of medications called DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors)
• Metformin belongs to a class of medications called biguanides.

They act together to control blood sugar levels in adult patients with a form of diabetes called “type 2 diabetes mellitus”.This medication helps to increase the levels of insulin produced after a meal and reduces the amount of sugar produced by the body.

Together with a diet and exercise, this medication helps to lower blood sugar levels.This medicationcan be used alone or with certain diabetes medications (insulin, sulfonylureas, or thiazolidinediones).

What is type 2 diabetes?

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

Do not take Estequen

• if you are allergic to sitagliptin, metformin, or any of the other ingredients in this medication (listed in section6)
• if you have severe kidney function impairment
• if you have uncontrolled diabetes, 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 ketone bodies accumulate in the blood, which can lead to diabetic precoma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or an unusual fruity odor on your breath
• if you have a severe infection or are dehydrated
• if you are scheduled to undergo a radiographythat requires the injection of a contrast agent.You will need to stop taking this medication at the time of the radiography and for 2 or more days afterwards, as instructed by your doctor, depending on your kidney function
• if you have recently had a heart attack or havesevere circulatory problems, such as “shock” or difficulty breathing
• if you have liver problems
• if you consume excessive amounts of alcohol (either daily or occasionally)
• if you are breastfeeding

Do not take this medication if any of the above circumstances apply to you and consult your doctor about other ways to control your diabetes. If you are unsure, consult your doctor, pharmacist, or nurse before starting to take this medication.

Warnings and precautions

Cases of pancreatitis have been reported in patients treated withthis medication(see section4).

If you notice blisters on your skin, it may be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop takingthis medication.

Risk of lactic acidosis

Sitagliptin/metforminmay cause a rare but 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 excessive alcohol consumption, dehydration (see below), 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).

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

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 intense vomiting, diarrhea, fever, exposure to heat, or if you drink less fluid than normal. 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 that produce 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.

Consult your doctor or pharmacist before starting to take this medication:

-if you have or have had pancreatitis (such as pancreatitis)

• if you have or have had gallstones, alcohol addiction, or have very high levels of triglycerides (a type of fat) in your blood. These medical conditions may increase your risk of developing pancreatitis (see section4)
• ifyou have type1 diabetes.This condition is also known asinsulin-dependent diabetes

• if you have or have had an allergic reaction to sitagliptin, metformin, or this medication (see section4)
• if you are taking a sulfonylurea or insulin, other diabetes medications, because you may experience hypoglycemia (low blood sugar). Your doctor may consider reducing the dose of the sulfonylurea or insulin you are taking

If you need to undergo major surgery, stop takingthis medicationwhile the procedure is being performed and for a period of time afterwards. Your doctor will decide when to stop and when to restart treatment withthis medication.

If you are unsure whether you are affected by any of the above circumstances, consult your doctor or pharmacist before starting to take this medication.

During treatment withsitagliptin/metformin, 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.

Children and adolescents

Children and adolescents under 18years should not use this medication. It is not effective in children and adolescents aged 10 to 17years. The safety and efficacy of this medication in children under 10years are unknown.

Other medications and Estequen

If you need to receive an injection of a contrast agent containing iodine, such as during a radiography or examination, stop takingsitagliptin/metforminbefore the injection or at the time of the injection. Your doctor will decide when to stop and when to restart treatment withsitagliptin/metformin.

Inform your doctor or pharmacist 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 ofsitagliptin/metformin. It is especially important to mention the following:

• medications (taken orally, inhaled, or injected) used to treat inflammatory conditions, such as asthma and arthritis (corticosteroids)
• medications that increase urine production (diuretics)
• medications used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• specific medicationsfor the treatment of bronchial asthma (β-adrenergic agonists)
• contrast agents containing iodine or medications containing alcohol
• specific medications used to treat stomach problems, such as cimetidine
• ranolazine, a medication used to treat angina pectoris
• dolutegravir, a medication used to treat HIV infection
• vandetanib, a medication used to treat a specific type of thyroid cancer (medullary thyroid cancer)
• digoxin (to treat irregular heartbeat and other heart problems). You may need to have your digoxin level checked in your blood if you are taking this medication withEstequen.

Taking Estequen with alcohol

Avoid excessive alcohol consumption while taking this medication, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medication.You should not take this medication during pregnancy or while breastfeeding. (See section2,Do not take Estequen).

Driving and operating machinery

The influence of this medication on your ability to drive and operate machinery is negligible or insignificant.However, cases of dizziness and somnolence have been reported during treatment with sitagliptin, which may affect your ability to drive and operate machinery.

Taking this medication with medications called sulfonylureas or with insulin may cause hypoglycemia, which may affect your ability to drive and operate machinery or work without a secure support.

Estequen contains sodium

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

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

Normally, you should take the tablets once a day at the time of dinner.

In some cases, your doctor may recommend that you take the tablets twice a day.

Take the tablets with food to reducethe likelihood of feeling stomach discomfort.

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

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

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

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

It is unlikely that treatment with this medication alone will cause an abnormal drop in blood sugar (hypoglycemia). A drop in blood sugar may occur when this medication is taken with a medication containing sulfonylurea or with insulin, so it is likely that your doctor will consider reducing the dose of your sulfonylurea or insulin.

If you take more Estequenthan you should

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

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

If you forgot to take Estequen

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 usual treatment.Do not take a double dose of this medication to compensate for the missed dose.

If you interrupt treatment withEstequen

Continue taking this medication all the time that your doctor tells you, to help you control your blood sugar level. Do not stop taking this medication without first consulting your doctor. If you interrupt treatment with this medication, your blood sugar may rise again.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

STOP taking sitagliptin/metformin and see your doctor immediately if you notice any of the following serious side effects:

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

Sitagliptin/metformin can cause a very rare but serious side effect (affects up to 1 in 10,000 people), called lactic acidosis (see "Warnings and precautions"). If this happens to you, you should stop taking this medicine and contact a doctor or the nearest hospital immediately, as lactic acidosis can lead to coma.

If you have a severe allergic reaction (frequency unknown: cannot be estimated from available data), including skin rash, urticaria, skin blisters/peeling 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 diabetes treatment.

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

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

Infrequent (affects 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 side effects when taking this medicine with a sulfonylurea such as glimepiride:

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

Frequent:constipation

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

Frequent: swelling of hands or feet

Some patients presented the following side 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 side effects during clinical studies while taking sitagliptin alone (one of the medicines contained in this medicine) or during use after approval of sitagliptin/metformina or sitagliptin alone or with other diabetes medicines:

Frequent:low blood sugar levels, headache,upper respiratory tract infection,nasal congestion or mucous, and sore throat, arthritis, arm or leg pain

Infrequent:dizziness, constipation, itching

Rare: reduced platelet count

Unknown frequency: kidney problems (which sometimes 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 side 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

Very rare:reduced vitamin B12 levels, hepatitis (liver problem), urticaria, skin redness (rash) or itching

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, 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 medicine.

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

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

This medication does not require special conditions for conservation.

Medications should not be disposed of 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 the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Estequen

• The active principles are sitagliptin and metformin.

Estequen50 mg/1.000 mg: Each tablet containssitagliptin hydrochloride monohydrate equivalent to50mg of sitagliptin and 1.000mg of metformin hydrochloride.

Estequen100 mg/1.000 mg: Each tablet containssitagliptin hydrochloride monohydrate equivalent to 100mg of sitagliptin and 1.000mg of metformin hydrochloride.

• The other components are:

- Prolonged-release coating of metformin: hypromellose, magnesium stearate.

- Immediate-release coating of sitagliptin: calcium phosphate, microcrystalline cellulose, stearate of fumaric acid and sodium, croscarmellose sodium (see section 2 “Estequencontains sodium”).

- In addition, the coating contains:

Estequen50 mg/1.000 mg: poly (vinyl alcohol), titanium dioxide (E171), macrogol 4000, talc

Estequen100 mg/1.000 mg: poly (partially hydrolyzed vinyl alcohol), titanium dioxide (E171), macrogol 4000, talc, yellow iron oxide (E172), red iron oxide (E172).

Appearance of the product and contents of the package

Estequen50mg/1.000mg are white, oval, biconvex tablets, 22.2 mm x 10.8 mm in size, with the inscription “50” on one face and “1000” on the other face.

Estequen100mg/1.000mg are orange, oval, biconvex tablets, 22.2 mm x 10.8 mm in size, with the inscription “100” on one face and “1000” on the other face.

PVC/PVDC/aluminum blisters.

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

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Teva Pharma, S.L.U.

c/Anabel Segura, 11 Edificio Albatros B, 1st floor

Alcobendas 28108 Madrid

Spain

Responsible 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

Last revision date of this leaflet: March 2022

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