Combodiab

Package Leaflet: Information for the Patient

COMBODIAB, 50 mg + 850 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.
• In case of any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their 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 type 2 diabetes mellitus. This medicine helps to increase the amount of insulin released after a meal and reduce the amount of sugar produced by the body. The medicine is used in combination with diet and exercise to reduce blood sugar levels. It can be used alone or in combination with certain other anti-diabetic medicines (insulin, sulfonylurea derivatives, 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 properly. 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, vision loss, and limb amputation.

2. Important information before taking Combodiab

When not to take Combodiab:

• if the patient is allergic to sitagliptin or metformin, or any of the other ingredients of this medicine (listed in section 6),
• if the patient has significantly reduced kidney function,
• if the patient has 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 diabetic ketoacidosis. Diabetic ketoacidosis is a condition in which substances called ketone bodies accumulate 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 the patient has a severe infection or dehydration,

• if the patient is scheduled to undergo a radiological examination with intravenous administration of a contrast agent. The patient should stop taking Combodiab during the radiological examination and for at least 2 days, according to the doctor's recommendations, depending on the patient's kidney function.
• if the patient has recently had a heart attack or has severe circulatory disorders, such as shock or breathing difficulties,
• if the patient has liver disease,
• if the patient consumes excessive amounts of alcohol (either daily or from time to time),
• if the patient is breastfeeding.

Do not take Combodiab if any of the above contraindications apply. Consult your doctor to determine other methods of controlling diabetes. In case of doubts, before taking Combodiab, discuss it with your doctor, pharmacist, or nurse.

Warnings and precautions

Patients taking Combodiab have reported cases of pancreatitis (see section 4). If the patient develops blisters on the skin, it may be a sign of a disease called pemphigoid blisters. The doctor may recommend stopping Combodiab.

Risk of lactic acidosis

Combodiab may cause a very rare but very serious side effect called lactic acidosis, especially if the patient has kidney problems. The risk of lactic acidosis increases in cases of uncontrolled diabetes, severe infection, prolonged fasting, or alcohol consumption, dehydration (see more information below), liver problems, and any conditions in which a part of the body is not adequately supplied with oxygen (e.g., severe heart disease). If any of these situations apply to the patient, they should consult their doctor for more detailed instructions.

Temporarily stop taking Combodiab if the patient has a condition that may lead to dehydration

(significant loss of body water), such as severe vomiting, diarrhea, fever, high temperature, or if the patient drinks less fluid than usual. The patient should consult their doctor for more detailed instructions.

Stop taking Combodiab and immediately contact your doctor or the nearest hospital if the patient experiences 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 slowed heart rate.

Lactic acidosis is a life-threatening condition that requires immediate hospital treatment. The patient should immediately contact their doctor to receive further instructions if:

• the patient has 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).
• the patient experiences any of the following symptoms after starting metformin: seizures, decreased cognitive abilities, difficulty moving, signs of nerve damage (e.g., pain or numbness), migraine, or hearing loss.

Before taking Combodiab, the patient should discuss the following with their doctor or pharmacist:

• if the patient has or has had pancreatitis (e.g., inflammation of the pancreas),
• if the patient has or has had gallstones, alcohol dependence, or very high triglyceride levels in the blood. In such cases, the risk of pancreatitis (see section 4) may increase.
• if the patient has type 1 diabetes. It is also known as insulin-dependent diabetes.
• if the patient has or has had allergic reactions to sitagliptin, metformin, or Combodiab (see section 4).
• if the patient is taking a sulfonylurea derivative or insulin, anti-diabetic medicines, in combination with Combodiab, as it may lead to excessive reduction of blood sugar levels (hypoglycemia). The doctor may reduce the dose of the sulfonylurea derivative or insulin.

If the patient is scheduled to undergo major surgery, they should not take Combodiab during the surgery and for some time after it. The doctor will decide when the patient should stop and resume taking Combodiab. In case of doubts, before taking Combodiab, the patient should discuss it with their doctor or pharmacist. During treatment with Combodiab, the doctor will monitor the patient's kidney function at least once a year or more frequently if the patient is elderly and/or has worsening kidney function.

Children and adolescents

This medicine should not be used in children and adolescents under 18 years of age. The medicine is not effective in children and adolescents aged 10 to 17 years. It is not known whether the medicine is safe and effective in children under 10 years of age.

Combodiab and other medicines

If the patient is to receive an intravenous contrast agent containing iodine, for example, for an X-ray examination or computed tomography, they should stop taking Combodiab before or at the latest at the time of administration. The doctor will decide when the patient should stop and resume taking Combodiab. The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. The patient may need more frequent blood sugar checks and kidney function tests or dose adjustments of Combodiab by the doctor. It is especially 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 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),
• specific medicines used to treat asthma (β-sympathomimetics),
• iodine-containing contrast agents 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 carcinoma),
• digoxin (used to treat heart rhythm disorders and other heart conditions). When taking Combodiab with digoxin, the patient's digoxin blood levels should be monitored.

Taking Combodiab with alcohol

The patient should avoid consuming excessive amounts of alcohol while taking Combodiab, as it may increase the risk of lactic acidosis (see "Warnings and precautions").

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor or pharmacist before taking this medicine. This medicine should not be used during pregnancy or 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, the patient should consider that dizziness and drowsiness have been reported in patients taking sitagliptin, which may affect the ability to drive and use machines. Taking this medicine in combination with sulfonylurea derivatives 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 of sodium (23 mg) per tablet, which means it is essentially "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.
• To control blood sugar levels, the doctor may increase the dose of Combodiab.
• If the patient has kidney problems, the doctor may prescribe a lower dose.

During treatment with this medicine, the patient should continue to follow the diet and exercise recommended by their doctor. It is unlikely that taking this medicine alone will lead to abnormally low blood sugar levels (hypoglycemia). Hypoglycemia may occur when taking this medicine in combination with a sulfonylurea derivative or insulin - in such cases, the doctor may reduce the dose of the sulfonylurea derivative or insulin. The score line on the tablet is not intended for breaking the tablet.

Taking a higher dose of Combodiab than recommended

If the patient takes more Combodiab than they should, they should immediately contact their doctor. They should go to the hospital if they experience symptoms of lactic acidosis, such as feeling cold or uncomfortable, severe nausea or vomiting, stomach pain, unexplained weight loss, muscle cramps, or rapid breathing (see "Warnings and precautions").

Missing a dose of Combodiab

If the patient misses a dose, they should take it as soon as possible. If it is almost time for the next dose, they should skip the missed dose and continue taking the medicine as usual. The patient should not take a double dose of this medicine.

Stopping treatment with Combodiab

To maintain control of blood sugar levels, the patient should take this medicine for as long as their doctor recommends. The patient should not stop taking this medicine without consulting their doctor first. Stopping treatment with Combodiab may lead to increased blood sugar levels. If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The patient should STOPtaking Combodiab and immediately contact their doctor if they experience any of the following serious side effects:

• 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 the patient, they should STOPtaking Combodiab and immediately contact their doctor or the nearest hospital, 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, as well as swelling of the face, lips, tongue, and throat, which may cause difficulty breathing or swallowing, the patient should stop taking the medicine and immediately contact their doctor. The doctor may prescribe a medicine to treat the allergic reaction and another medicine (change the medicine) to treat diabetes. Some patients taking metformin after starting sitagliptin have experienced the following side effects: Common (may affect up to 1 in 10 people): low blood sugar levels, nausea, bloating, vomiting Uncommon (may affect up to 1 in 100 people): stomach pain, diarrhea, constipation, drowsiness Some patients have experienced diarrhea, nausea, bloating, constipation, stomach pain, or vomiting after starting sitagliptin in combination with metformin (common). Some patients taking this medicine in combination with a sulfonylurea derivative, such as glimepiride, have experienced the following side effects: Very common (may affect more than 1 in 10 people): low blood sugar levels Common: constipation Some patients taking this medicine in combination with pioglitazone have experienced the following side effects: Common: swelling of the hands or feet Some patients taking this medicine in combination with insulin have experienced the following side effects: Very common: low blood sugar levels Uncommon: dry mouth, headache In clinical trials, some patients taking sitagliptin (one of the active substances of Combodiab) alone or in combination with other anti-diabetic medicines have experienced the following side effects: Common: low blood sugar levels, headache, upper respiratory tract infection, stuffy or runny nose, and sore throat Uncommon: dizziness, constipation, itching Rare (may affect up to 1 in 1,000 people): reduced platelet count Frequency not known: kidney disease (sometimes requiring dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, pemphigoid blisters (a type of blisters on the skin) Some patients taking metformin alone have experienced the following side effects: Very common: nausea, vomiting, diarrhea, stomach pain, and loss of appetite. These symptoms may occur after starting metformin and usually disappear. Common: metallic taste, reduced or low vitamin B12 levels in the blood (symptoms may include extreme fatigue, pain, and redness of the tongue, numbness or tingling, or pallor or yellowing of the skin). The doctor may order some tests to find the cause of the symptoms, as some of them may also be caused by diabetes or other unrelated health problems. Very rare: liver inflammation (liver disease), hives, skin redness (rash), or itching

Reporting side effects

If the patient experiences any side effects, including any not listed in this leaflet, they should tell their 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, more information can be collected 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. The patient should ask their pharmacist how to dispose of medicines they no longer need. This will help protect the environment.

6. Contents of the pack and other information

What Combodiab contains

• The active substances are sitagliptin and metformin. Each film-coated tablet contains sitagliptin hydrochloride monohydrate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
• The other ingredients are: povidone K29/32, microcrystalline cellulose, crospovidone (Kollidon), and sodium stearyl fumarate. The tablet coating also contains: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, yellow iron oxide (E 172), red iron oxide (E 172), and black iron oxide (E 172).

What Combodiab looks like and contents of the pack

Pink, elongated, oval film-coated tablets with a score line on one side and "SA" on the other side. The tablet diameter is 19.5 mm ± 0.5 mm. The pack contains 56 film-coated tablets in a PVC/PVDC/Aluminum blister pack in a cardboard box.

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, please contact:

BIOTON S.A.
02-516 Warsaw
ul. Starościńska 5
Tel: + 48 (22) 721 40 00
[email protected]

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

Malta: COMBODIAB 50mg/850 mg film-coated tablets
Poland: COMBODIAB
Date of last revision of the package leaflet:April 2025