Package Insert: Information for the Patient

Metsunix 50 mg/500 mg Modified-Release Tablets

Metsunix 50 mg/1.000 mg Modified-Release Tablets

Metsunix 100 mg/1.000 mg Modified-Release Tablets

sitagliptin/metformin hydrochloride

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, 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 adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert.See section 4.

Metsunix contains 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 work 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.

Along with diet and exercise, this medication helps to lower blood sugar levels. This medication can 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 Metsunix

• if you are allergic to sitagliptin, metformin, or any of the other components of this medication (listed in section 6).
• if you have severe kidney function reduction.
• 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 substances called "ketone bodies" accumulate in the blood, which can lead to diabetic precoma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or if your breath develops an unusual fruity odor.
• if you have a severe infection or are dehydrated.
• if you are scheduled to undergo a radiography that 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 the functioning of your kidneys.
• if you have recently had a heart attack or have severe circulatory problems, such as "shock" or difficulty breathing.
• if you have liver problems (hepatic).
• if you drink excessive alcohol (whether 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

Consult your doctor, pharmacist, or nurse before starting to take this medication.

Cases of pancreatitis have been reported in patients treated with this medication (see section 4).

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

Risk of lactic acidosis

This medication may cause a rare but serious side effect called lactic acidosis, especially if your kidneys do not function 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 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 this medication 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 this medication 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.
• abdominal pain (stomach 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.
• 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 section 4).
• if you have type 1 diabetes. This disease is also known as insulin-dependent diabetes.
• if you have or have had an allergic reaction to sitagliptin, metformin, or the combination of sitagliptin/metformin (see section 4).
• if you are taking a sulfonylurea or insulin, other diabetes medications, as you may experience low blood sugar (hypoglycemia). Your doctor may consider reducing the dose of the sulfonylurea or insulin you are taking.

If you need to undergo major surgery, stop taking this medication while the procedure is being performed and for a period of time afterwards. Your doctor will decide when to interrupt treatment with this medication and when to restart it.

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 with this medication, 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 deteriorating.

Children and adolescents

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

Other medications and Metsunix

If you need to receive an injection of a contrast agent containing iodine, such as during a radiography or examination, stop taking this medication before the injection or at the time of the injection. Your doctor will decide when to interrupt treatment with this medication and when to restart it.

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 of this medication. It is especially important to mention the following:

• medications (taken orally, inhaled, or injected) used to treat inflammatory diseases, 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 medications used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).
• medications specifically used to treat bronchial asthma (β-adrenergic agonists).
• iodinated contrast agents 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.

Taking Metsunix 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. Do not take this medication during pregnancy or while breastfeeding. See section 2, Do not take Metsunix.

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 insulin may cause hypoglycemia, which may affect your ability to drive and operate machinery or work without a secure support.

Metsunix 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 indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again. Your doctor will tell you how many tablets of this medication you should take and when you should take them.

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

You should normally take the tablets once a day, with dinner.

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

Always take the tablets with food to reduce the possibility of stomach pain.

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

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

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

You should 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 Metsunix than 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, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Metsunix

If you forget to take a dose, take it as soon as you remember. If you do not remember until your next dose time, skip the missed dose and continue with your regular treatment. Do not take a double dose to compensate for missed doses.

If you interrupt treatment with Metsunix

Continue taking this medication all the time your doctor tells you to, 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 level may increase 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 this medicine 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 of the pancreas).

This medicine can cause a very rare but serious side effect (can affect up to 1 in 10,000 people), called lactic acidosis (see "Warnings and precautions"). If this happens to you,you must 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 since it cannot be estimated from available data), including skin rash, urticaria, blisters on the skin/skin peeling 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:

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

Uncommon (can 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 common).

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

Very common (can affect more than 1 in 10 people): low blood sugar.

Common: constipation.

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

Common: swelling of hands or feet.

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

Very common: low blood sugar.

Uncommon: dry mouth, headache.

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

Common: low blood sugar, headache, upper respiratory tract infection, congestion or nasal mucus, and sore throat, arthritis, arm or leg pain.

Uncommon: 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 blister on the skin).

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

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

Common: 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 possible side effects that do not appear in this prospectus. 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 container after CAD. The expiration date is the last day of the month indicated.

This medication does not require special conservation conditions.

Medications should not be disposed of through drains or in the trash. Dispose of the containers and medications you no longer need at the SIGRE collection point of the pharmacy. Ask your pharmacist how to dispose of the containers and medications you no longer need.This will help protect the environment.

Composition of Metsunix

The active principles are sitagliptin and metformin.

Metsunix 50 mg/500 mg: Each tablet contains sitagliptin hydrochloride monohydrate (equivalent to 50 mg of sitagliptin) and 500 mg of metformin hydrochloride.

Metsunix 50 mg/1.000 mg: Each tablet contains sitagliptin hydrochloride monohydrate (equivalent to 50 mg of sitagliptin) and 1.000 mg of metformin hydrochloride.

Metsunix 100 mg/1.000 mg: Each tablet contains sitagliptin hydrochloride monohydrate (equivalent to 100 mg of sitagliptin) and 1.000 mg of metformin hydrochloride.

The other components (excipients) are:

• Extended-release metformin coating:hypromellose, magnesium stearate.
• Immediate-release sitagliptin coating: calcium hydrogen phosphate, microcrystalline cellulose, stearic acid and sodium fumarate, and croscarmellose sodium (see section 2 “Metsunix contains sodium”).
• Additionally,the film coatingcontains:
• • Metsunix 50 mg/500 mg and Metsunix 100 mg/1.000 mg: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, talc, yellow iron oxide (E172), and red iron oxide (E172).
  • Metsunix 50 mg/1.000 mg: polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, and talc.

Appearance of the product and contents of the package

Metsunix 50 mg/500 mg: Orange-coated, oval, biconvex tablet, 17.2 mm x 8.4 mm in size.

Metsunix 50 mg/1.000 mg: White-coated, oval, biconvex tablet, 22.2 mm x 10.8 mm in size, marked with the number “50” on one side and “1000” on the other.

Metsunix 100 mg/1.000 mg: Orange-coated, oval, biconvex tablet, 22.2 mm x 10.8 mm in size, marked with the number “100” on one side and “1000” on the other.

PVC/PVDC-Aluminum blisters. Packages of 28, 30, 56, and 60 modified-release tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Adamed Laboratorios, S.L.U.

c/ de las Rosas de Aravaca, 31 - 2nd floor

28023 Madrid

Responsible for manufacturing

Adamed Pharma S.A.

ul. Marszalka Józefa Pilsudskiego 5

95-200 Pabianice

Poland

This medicinal product is authorizedinthe member states of the European Economic Area with the following names:

Last revision date of this leaflet: February 2022

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