SITAGLIPTIN/METFORMIN OPKO 50 mg/850 mg FILM-COATED TABLETS

Introduction

Package Leaflet:information for the patient

Sitagliptin/MetforminOPKO 50 mg/850 mg film-coated tablets EFG

Sitagliptin/Metformin OPKO 50 mg/1000 mg film-coated tablets EFG

sitagliptin/metformin hydrochloride

Read all of this 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 further questions, ask your doctor, pharmacist, or nurse.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Sitagliptin/Metformin OPKO is and what it is used for
2. What you need to know before you take Sitagliptin/Metformin OPKO
3. How to take Sitagliptin/Metformin OPKO
4. Possible side effects

5 Storage of Sitagliptin/Metformin OPKO

1. Package contents and additional information

1. What Sitagliptin/Metformin OPKO is and what it is used for

Sitagliptin/Metformin OPKO contains two different medicines called sitagliptin and metformin.

• sitagliptin belongs to a class of medicines called DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors)
• metformin belongs to a class of medicines called biguanides.

They work together to control blood sugar levels in adult patients with a form of diabetes called “type 2 diabetes mellitus”. This medicine helps increase the amount of insulin 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 with certain diabetes medicines (insulin, sulfonylureas, or glitazones).

What is type 2 diabetes?

Type 2 diabetes is a disease 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 (cardiac) problems, kidney (renal) problems, blindness, and amputations.

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

Do not take Sitagliptin/Metformin OPKO

• if you are allergic to sitagliptin or 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 an unusual fruity odor to your 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 this medicine 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)
• if you drink excessive amounts of alcohol (either every day or only occasionally)
• if you are breast-feeding.

Do not take this medicine 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 this medicine.

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 OPKO.

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

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

Stop taking Sitagliptin/Metformin OPKO 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 OPKO 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 should be treated in a hospital.

Consult your doctor promptly to advise you on how to proceed if:

• You know you have a genetic disorder that affects the mitochondria (the energy-producing components within cells), such as MELAS syndrome (mitochondrial encephalomyopathy, 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: seizure, cognitive impairment, difficulty with body movements, symptoms indicative of nerve damage (e.g., pain or numbness), migraine, and deafness.

Consult your doctor or pharmacist before taking Sitagliptin/Metformin OPKO:

• if you have or have had pancreatitis (inflammation of the pancreas)
• if you have or have had gallstones, alcohol dependence, 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 known as 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 it necessary to reduce the dose of the sulfonylurea or insulin you are taking

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 this medicine.

During treatment with this medicine, 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 of age 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 of age.

Other medicines andSitagliptin/Metformin OPKO

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 this medicine before or at the time of the injection. Your doctor will decide when you should stop taking this medicine 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 your digoxin levels if you are taking Sitagliptin/Metformin.

TakingSitagliptin/Metformin OPKOalcohol

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

Pregnancy andbreast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. You should not take this medicine during pregnancy. Do not take this medicine if you are breast-feeding. See section 2 “Do not take Sitagliptin/Metformin OPKO”.

Driving and using machines

The effect of this medicine on your ability to drive and 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 and use machines.

Taking this medicine with sulfonylureas or insulin may cause hypoglycemia, which may affect your ability to drive and use machines or work without a secure support.

Sitagliptin/Metformin OPKOcontains sodium

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

3. How to take Sitagliptin/Metformin OPKO

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

• Take one tablet:
• • twice a day by mouth
  • with food to reduce the chance 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 (hypoglycemia). Low blood sugar can occur when this medicine is taken with a sulfonylurea or insulin, so your doctor may consider it necessary to reduce the dose of your sulfonylurea or insulin.

If you take more Sitagliptin/Metformin OPKO than you should

If you take more of 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”).

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 forget to take Sitagliptin/Metformin OPKO

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 normal treatment schedule. Do not take a double dose to make up for missed doses.

If you stop taking Sitagliptin/Metformin OPKO

Keep taking this medicine for as long as your doctor tells you to, so it can help control your blood sugar levels. Do not stop taking this medicine without first talking to your doctor. If you stop taking Sitagliptin/Metformin, your blood sugar levels may increase again.

If you have any further questions on the use of this medicine, 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 takingSitagliptina/MetforminaOPKO and go to the doctor immediatelyif 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 (inflammation of the pancreas).

Sitagliptina/Metformina 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 this medicineand 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/desquamation 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 sitagliptina:

Frequent(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 sitagliptina and metformina (frequency classified as frequent).

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

Very Common(may affect more than 1 in 10 people):

• low blood sugar levels

Frequent(may affect up to 1 in 10 people):

• constipation

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

Frequent(may affect up to 1 in 10 people):

• swelling of hands or feet

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

Very Common(may affect more than 1 in 10 people):

• low blood sugar levels

Uncommon(may affect up to 1 in 100 people):

• dry mouth,
• headache

Some patients have experienced the following adverse effects during clinical studies while taking sitagliptina alone (one of the medicines that contains this medicine) or during use after the approval of Sitagliptina/Metformina or sitagliptina alone or with other diabetes medicines:

Frequent(may affect up to 1 in 10 people):

• low blood sugar levels,
• headache,
• upper respiratory tract infection,
• nasal congestion or runny nose and sore throat,
• arthrosis,
• pain in the arm or leg

Uncommon(may affect up to 1 in 100 people):

• dizziness,
• constipation,
• itching

Rare(may affect up to 1 in 1000 people):

• reduction in platelet count

Frequency not known(cannot be estimated from the available data):

• 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 Common(may affect more than 1 in 10 people):

• nausea,
• vomiting,
• diarrhea,
• stomach pain and loss of appetite.

These symptoms may appear when you start taking metformin and usually disappear

Frequent(may affect up to 1 in 10 people):

• metallic taste
• decrease or low levels of vitamin B12 in blood (symptoms may include extreme fatigue).
• pain and redness of the tongue (glossitis)
• tingling (paresthesia) or pale or yellowish skin)
• Your doctor may request tests to determine the cause of your symptoms because some of them can also be caused by diabetes or other unrelated health problems.

Very Rare(may affect more than 1 in 10,000 people):

• 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, pharmacist, or nurse, 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. Storage of Sitagliptina/Metformina OPKO

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

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

Do not store above 30°C.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and medicines that you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Sitagliptina/Metformina OPKO

• The active ingredients are sitagliptina and metformina

• Each film-coated tablet contains sitagliptina tartrate hemihydrate equivalent to 50 mg of sitagliptina and 850 mg of metformina hydrochloride.
• Each film-coated tablet contains sitagliptina tartrate hemihydrate equivalent to 50 mg of sitagliptina and 1000 mg of metformina hydrochloride

• The other components are:

• Tablet core: microcrystalline cellulose (E460), povidone K-30 (E1201), sodium croscarmellose (E468), sodium lauryl sulfate, and sodium stearyl fumarate,
• Film coating: polyvinyl alcohol (E1203), macrogol 3350 (E1521), talc (E553b), titanium dioxide (E171), red iron oxide (E172), black iron oxide (E172).

Appearance of the Product and Package Contents

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

Film-coated tablet, pink in color, capsule-shaped, and with the inscription “K21” on one side and smooth on the other side.

Dimensions – Length: 20.1 mm ± 0.2 mm; Width: 9.8 mm ± 0.2 mm

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

Film-coated tablet, capsule-shaped, red in color, and with the inscription “K22” on one side and smooth on the other side.

Dimensions – Length: 21.4 mm ± 0.2 mm; Width: 10.5 mm ± 0.2 mm

Cold-formed laminated blister pack (OPA/ALU/PVC) with aluminum foil. Packages of 56 and 196 film-coated tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

OPKO Health Spain S.L.U.

Pl. Europa 13-15, 08908

L'Hospitalet de Llobregat, (Barcelona)

Spain

Manufacturer

Synoptis Industrial Sp. z o.o

ul. Rabowicka 15, Swarzedz,

62-020, Poland

Date of the Last Revision of thisProspectus: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/)