Combodiab

Package Leaflet: Information for the Patient

COMBODIAB 50 mg + 1000 mg film-coated tablets

Sitagliptin + Metformin hydrochloride

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this package leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Combodiab and what is it used for
• 2. Important information before taking Combodiab
• 3. How to take Combodiab
• 4. Possible side effects
• 5. How to store Combodiab
• 6. Contents of the pack and other information

1. What is Combodiab and what is it used for

Combodiab contains two different active substances called sitagliptin and metformin.

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

The combined action of these medicines leads to the normalization of blood sugar levels in adult patients with a type of diabetes known as "type 2 diabetes". This medicine helps to increase the amount of insulin released after a meal and decreases the amount of sugar produced by the body. When taken in combination with diet and exercise, this medicine helps to lower blood sugar levels. It can be used alone or in combination with certain other anti-diabetic medicines (insulin, sulfonylureas, or glitazones).

What is type 2 diabetes?

In type 2 diabetes, the body does not produce enough insulin, and the insulin produced does not work as it should. The body may also produce too much sugar. If this happens, sugar (glucose) builds up in the blood. This can lead to serious health problems, such as heart disease, kidney disease, loss of vision, and limb amputation.

2. Important information before taking Combodiab

When not to take Combodiab:

• if you are allergic to sitagliptin or metformin, or any of the other ingredients of this medicine (listed in section 6),
• if you have significantly reduced kidney function,
• if you have uncontrolled diabetes, such as severe hyperglycemia (high blood sugar levels), nausea, vomiting, diarrhea, sudden weight loss, or acidosis (see "Risk of lactic acidosis" below) or ketoacidosis. Ketoacidosis is a condition in which substances called ketone bodies build up in the blood and can lead to diabetic pre-coma. Symptoms include abdominal pain, rapid and deep breathing, drowsiness, or an unusual fruity odor from the mouth.

if you have a severe infection or dehydration,

• if you are going to have a radiological examination with intravenous contrast medium. You should stop taking Combodiab during the examination and for 2 or more days, as recommended 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 disease,
• if you drink excessive amounts of alcohol (either regularly or from time to time),
• if you are breastfeeding.

Do not take Combodiab if any of the above contraindications apply to you. Consult your doctor to determine other methods of controlling your diabetes. If in doubt, discuss with your doctor, pharmacist, or nurse before taking Combodiab.

Warnings and precautions

Patients taking Combodiab have reported cases of pancreatitis (see section 4). If you experience blisters on your skin, it may be a sign of a condition called bullous pemphigoid. Your doctor may advise you to stop taking Combodiab.

Risk of lactic acidosis

Combodiab may cause a very rare but very serious side effect called lactic acidosis, especially if you have kidney problems. The risk of lactic acidosis increases if you have uncontrolled diabetes, severe infection, prolonged fasting, or excessive alcohol consumption, dehydration (see below), liver problems, or any condition that affects the supply of oxygen to the body (e.g., severe heart disease). If any of these situations apply to you, consult your doctor for more detailed instructions.

Temporarily stop taking Combodiab if you have a condition that may lead to dehydration

(significant loss of body water), such as severe vomiting, diarrhea, fever, high temperature, or if you drink less fluid than usual. Consult your doctor for more detailed instructions.

Stop taking Combodiab and contact your doctor or the nearest hospital immediately if you experience

any symptoms of lactic acidosis, as this condition can lead to coma. Symptoms of lactic acidosis include:

• vomiting,
• abdominal pain,
• muscle cramps,
• general feeling of being unwell, combined with severe fatigue,
• breathing difficulties,
• decreased body temperature and slow heart rate.

Lactic acidosis is a life-threatening condition that requires immediate hospital treatment. If you experience any of the above symptoms, contact your doctor immediately. If you have a genetically inherited disease affecting the mitochondria (energy-producing structures in cells), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD), inform your doctor.

• If you experience any of the following symptoms after starting metformin: seizures, impaired cognitive function, difficulty moving, signs of nerve damage (e.g., pain or numbness), migraine, or hearing loss.

Before taking Combodiab, discuss with your doctor or pharmacist:

• if you have or have had pancreatitis (inflammation of the pancreas),
• if you have or have had gallstones, alcohol dependence, or very high levels of triglycerides (a type of fat) in the blood. In these situations, the risk of pancreatitis (see section 4) may increase.
• if you have type 1 diabetes. It is also known as insulin-dependent diabetes.
• if you have or have had allergic reactions to sitagliptin, metformin, or Combodiab (see section 4).
• if you are taking a sulfonylurea or insulin, anti-diabetic medicines, at the same time as Combodiab, as this may lead to low blood sugar levels (hypoglycemia). Your doctor may reduce the dose of the sulfonylurea or insulin.

If you are going to have a major surgical procedure, you should not take Combodiab during the procedure and for some time after it. Your doctor will decide when you should stop and restart Combodiab treatment. If in doubt, discuss with your doctor or pharmacist before taking Combodiab. During treatment with Combodiab, your doctor will monitor your kidney function at least once a year or more often if you are elderly and/or have worsening kidney function.

Children and adolescents

Do not use this medicine in children and adolescents under 18 years of age. This medicine is not effective in children and adolescents aged 10 to 17 years. It is not known whether this medicine is safe and effective when used in children under 10 years of age.

Combodiab and other medicines

If you are going to have an intravenous contrast medium containing iodine, for example, for an X-ray examination or computed tomography, you should stop taking Combodiab before or at the latest at the time of the examination. Your doctor will decide when you should stop and restart Combodiab treatment. Tell your doctor or pharmacist about all the medicines you are taking or have recently taken, as well as any medicines you plan to take. You may need more frequent blood glucose monitoring and kidney function tests or dose adjustments of Combodiab by your doctor. It is particularly important to inform about the following medicines:

• medicines (taken orally, inhaled, or injected) used to treat inflammatory diseases, such as asthma or arthritis (corticosteroids),
• diuretics (medicines that increase urine production),
• medicines used to treat pain and inflammation [non-steroidal anti-inflammatory drugs (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),

sulfonamide-containing medicines (used to treat bacterial infections),

• specific medicines used to treat asthma (β-sympathomimetics),
• iodine-containing contrast media or alcohol-containing medicines,
• certain medicines used to treat stomach disorders, such as cimetidine,
• ranolazine, a medicine used to treat angina,
• dolutegravir, a medicine used to treat HIV infection,
• vandetanib, a medicine used to treat a certain type of thyroid cancer (medullary thyroid cancer),
• digoxin (used to treat heart rhythm disorders and other heart conditions). When taking Combodiab with digoxin, monitor digoxin blood levels.

Taking Combodiab with alcohol

Avoid excessive alcohol consumption while taking Combodiab, as this may increase the risk of lactic acidosis (see "Warnings and precautions").

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Do not take this medicine during pregnancy or while breastfeeding. See section 2, When not to take Combodiab.

Driving and using machines

This medicine has no or negligible influence on the ability to drive and use machines. However, when driving or using machines, consider that dizziness and drowsiness have been reported with sitagliptin, which may affect the ability to drive and use machines. Taking this medicine with sulfonylureas or insulin may lead to hypoglycemia, which may affect the ability to drive and use machines or work without safe foot support.

Combodiab contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, which is considered to be "sodium-free".

3. How to take Combodiab

Always 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, orally;
• with meals to reduce the likelihood of stomach upset.
• Your doctor may increase the dose of Combodiab to control blood sugar levels.
• If you have kidney problems, your doctor may prescribe a lower dose.

While taking this medicine, continue to follow the diet and exercise regimen recommended by your doctor. It is unlikely that taking this medicine alone will lead to low blood sugar levels (hypoglycemia). Low blood sugar levels may occur when taking this medicine with a sulfonylurea or insulin - in this case, your doctor may reduce the dose of the sulfonylurea or insulin. The score line on the tablet is not intended to break the tablet.

Taking a higher dose of Combodiab than recommended

If you take more Combodiab than you should, contact your doctor immediately. Go to the hospital if you experience symptoms of lactic acidosis, such as feeling cold or uncomfortable, severe nausea or vomiting, abdominal pain, unexplained weight loss, muscle cramps, or rapid breathing (see "Warnings and precautions").

Missing a dose of Combodiab

If you miss a dose, take it as soon as possible. If it is almost 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.

Stopping treatment with Combodiab

To maintain control of blood sugar levels, you should continue to take this medicine for as long as your doctor recommends. Do not stop taking this medicine without consulting your doctor first. Stopping Combodiab treatment may lead to an increase in blood sugar levels. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you experience any of the following serious side effects, stop taking Combodiab and contact your doctor immediately:

• Severe and persistent abdominal pain (in the stomach area), which may radiate to the back, with or without nausea and vomiting - these may be symptoms of pancreatitis.

Combodiab may very rarely cause (may affect up to 1 in 10,000 people) a very serious side effect called lactic acidosis (see "Warnings and precautions"). If this happens to you, stop taking Combodiab and contact your doctor or the nearest hospital immediately, as lactic acidosis can lead to coma. In case of a severe allergic reaction (frequency not known), including rash, hives, blisters on the skin, or peeling of the skin, and swelling of the face, lips, tongue, or throat, which may cause difficulty breathing or swallowing, stop taking Combodiab and contact your doctor immediately. Your doctor may prescribe a medicine to treat the allergic reaction and another medicine to treat diabetes. Some patients taking metformin after starting sitagliptin experienced the following side effects:

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

Uncommonly (may affect up to 1 in 100 people): abdominal pain, diarrhea, constipation, drowsiness

Some patients experienced diarrhea, nausea, bloating, constipation, abdominal pain, or vomiting after starting sitagliptin in combination with metformin (frequently). Some patients taking Combodiab with a sulfonylurea, such as glimepiride, experienced the following side effects:

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

Frequently: constipation

Some patients taking Combodiab with pioglitazone experienced the following side effects:

Frequently: swelling of the hands or feet

Some patients taking Combodiab with insulin experienced the following side effects:

Very frequently: low blood sugar levels

Uncommonly: dry mouth, headache

In clinical trials, some patients taking sitagliptin (one of the active substances in Combodiab) alone or in combination with other anti-diabetic medicines experienced the following side effects:

Frequently: low blood sugar levels, headache, upper respiratory tract infection, stuffy or runny nose, sore throat, osteoarthritis, pain in the arms or legs

Uncommonly: dizziness, constipation, itching

Rarely (may affect up to 1 in 1,000 people): decreased platelet count

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

Some patients taking metformin alone experienced the following side effects:

Very frequently: nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These symptoms usually disappear after starting metformin.

Frequently: metallic taste, decreased or low levels of vitamin B12 in the blood (symptoms may include extreme fatigue, pain, and redness of the tongue, numbness or tingling, or pallor or yellowing of the skin). Your doctor may order tests to find the cause of the symptoms you are experiencing, as some of them may also be caused by diabetes or other unrelated health problems.

Very rarely: liver inflammation (liver disease), hives, skin rash, or itching

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Combodiab

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

Do not use this medicine after the expiry date stated on the blister and carton after "EXP". The expiry date refers to the last day of the month.

Store in a temperature below 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Combodiab contains

• The active substances are sitagliptin and metformin hydrochloride. Each film-coated tablet contains sitagliptin phosphate monohydrate equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.
• The other ingredients are: povidone K29/32, microcrystalline cellulose, crospovidone, and sodium stearyl fumarate. The tablet coating also contains: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, iron oxide red (E 172), and iron oxide black (E 172).

What Combodiab looks like and contents of the pack

Red to brownish, elongated, oval film-coated tablets with a score line between "S" and "B" on one side and a score line on the other side. The diameter of the tablet is 21.3 mm ± 0.5 mm. The pack contains 56 film-coated tablets in a PVC/PVDC/Aluminum blister pack in a carton.

Marketing authorization holder and manufacturer

Marketing authorization holder

BIOTON S.A.

ul. Starościńska 5

02-516 Warsaw

Poland

Manufacturer

SAG Manufacturing, S.L.U.

Ctra. N-I, Km 36

28750 San Agustín de Guadalix, Madrid

Spain

Galenicum Health, S.L.U.

Sant Gabriel, 50,

08950 Esplugues de Llobregat, Barcelona

Spain

For more information about this medicine, contact:

BIOTON S.A.

02-516 Warsaw

ul. Starościńska 5

Tel: + 48 (22) 721 40 00

bioinfo@bioton.com

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Malta: COMBODIAB 50mg/1000 mg film-coated tablets

Poland: COMBODIAB

Date of last revision of the package leaflet:April 2025