Combodiab

Patient Information Leaflet

COMBODIAB 50 mg + 1000 mg film-coated tablets
Sitagliptin + Metformin hydrochloride
Please read the entire leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual only. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Combodiab is and what it is 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 Combodiab is and what it is used for

Combodiab contains two different active substances: 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 two substances helps regulate blood glucose levels in adult patients with diabetes known as "type 2 diabetes." This medicine helps increase insulin release after meals and reduces the amount of glucose produced by the body.
When used together with diet and exercise, this medicine helps lower blood glucose levels. It may be used as the only antidiabetic treatment or in combination with certain other antidiabetic medicines (insulin, sulfonylureas, or glitazones).

What is type 2 diabetes?
In type 2 diabetes, the body does not produce enough insulin, and the insulin that is produced does not work properly. The body may also produce too much glucose. When this occurs, sugar (glucose) accumulates in the blood. This may lead to serious health problems such as heart disease, kidney disease, vision loss, and limb amputations.

2. Important information before taking Combodiab

When not to take Combodiab:

• if the patient is allergic to sitagliptin or metformin, or to 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, for example severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, sudden 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 and which may lead to diabetic pre-coma. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness or an unusual fruity odour of the breath.

• if the patient has a severe infection or dehydration,

• if the patient is scheduled for a radiological examination with intravascular administration of contrast medium. The use of Combodiab must be temporarily discontinued during the radiological examination and for 2 or more days thereafter, as directed by the physician, depending on the patient's kidney function.

• if the patient has recently suffered 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 occasionally),

• if the patient is breastfeeding.

Do not take Combodiab if any of the above contraindications apply.
Consult a doctor to determine alternative methods of diabetes control. In case of doubt, discuss this with your doctor, pharmacist, or nurse before taking Combodiab.
Warnings and precautions
Cases of pancreatitis have been reported in patients taking Combodiab (see section 4).
If the patient develops skin blisters, this may be a symptom of a condition known as bullous pemphigoid. The doctor may advise the patient to discontinue taking Combodiab.
Risk of lactic acidosis
Combodiab may cause a very rare but serious adverse effect known as lactic acidosis, especially if the patient has impaired kidney function. The risk of lactic acidosis increases in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more detailed information below), liver dysfunction, and any medical conditions in which a part of the body is inadequately supplied with oxygen (e.g. acute severe heart disease).
If any of the above conditions apply to the patient, consult a doctor for further instructions.
Temporarily discontinue Combodiab if the patient develops a medical condition that may involve dehydration (significant loss of water from the body), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if the patient drinks less fluid than usual. Consult a doctor for further instructions.
Discontinue Combodiab and contact a doctor or the nearest hospital immediately if the patient experiences any symptoms of lactic acidosis, as this condition may lead to coma.
Symptoms of lactic acidosis include:

• vomiting,
• abdominal pain,
• muscle cramps,
• general malaise accompanied by profound fatigue,
• difficulty breathing,
• decreased body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring immediate hospital treatment.
Contact a doctor immediately for further instructions if:

• the patient has a genetically inherited mitochondrial disorder (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).
• after starting metformin, the patient experiences any of the following symptoms: seizures, worsening cognitive function, difficulty moving, signs indicating nerve damage (e.g. pain or numbness), migraine, or deafness.

Before starting Combodiab, discuss the following with your doctor or pharmacist:

• if the patient has or has had pancreatic disease (e.g. pancreatitis),
• if the patient has or has had gallstones, alcohol dependence, or very high triglyceride levels (a type of fat) in the blood. In such cases, the risk of pancreatitis may increase (see section 4).
• if the patient has type 1 diabetes, sometimes referred to as insulin-dependent diabetes.
• if the patient currently has or has previously experienced allergic reactions to sitagliptin, metformin, or Combodiab (see section 4).
• if the patient is taking a sulphonylurea derivative or insulin, antidiabetic medicines together with Combodiab, as this may lead to excessively low blood glucose levels (hypoglycaemia). The doctor may reduce the dose of the sulphonylurea derivative or insulin.

If the patient is undergoing major surgery, Combodiab must not be taken during the procedure and for some time afterwards. The doctor will decide when the patient should stop and resume treatment with Combodiab.
In case of doubt, discuss this with your doctor or pharmacist before taking Combodiab.
While being treated 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 deteriorating kidney function.
Children and adolescents
This medicine must not be used 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 unknown whether this medicine is safe and effective when used in children under 10 years of age.
Combodiab and other medicines
If the patient is to receive an iodine-containing contrast medium injected into the bloodstream, for example for an X-ray or CT scan, the patient must stop taking Combodiab before or at the latest at the time of such injection. The doctor will decide when the patient should stop and resume treatment with Combodiab.
Inform your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. The patient may require more frequent monitoring of blood glucose levels and kidney function assessments, or dose adjustments of Combodiab by the doctor. It is especially important to inform about the following medicines:

• medicines (taken orally, by inhalation, or by injection) used to treat inflammatory conditions such as asthma or arthritis (corticosteroids),
• medicines that increase urine production (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 bronchial asthma (β-sympathomimetics),
• iodine-containing contrast media or medicines containing alcohol,
• some medicines used to treat gastrointestinal problems, 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 specific type of thyroid cancer (medullary thyroid cancer),
• digoxin (used to treat heart rhythm disorders and other heart conditions). Blood digoxin levels should be monitored when Combodiab is taken with digoxin.
  Alcohol consumption with Combodiab
  Avoid consuming excessive amounts of alcohol while taking Combodiab, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before taking this medicine. This medicine must not be used during pregnancy or while breastfeeding. See section 2, When not to take Combodiab.
Driving and operating machinery
This medicine has no effect or a negligible effect on the ability to drive and operate machinery. However, when driving and operating machinery, consider that dizziness and drowsiness have been reported with sitagliptin use, which may affect the ability to drive and operate machinery.
Taking this medicine together with medicines called sulphonylurea derivatives or insulin may lead to hypoglycaemia, which in turn may affect the ability to drive and operate machinery or work without secure foot support.
Combodiab contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet; therefore, this medicine is considered "sodium-free".

3. How to take Combodiab

This medicine should always be taken as prescribed by your doctor. If in doubt, consult your
doctor or pharmacist.

• Take one tablet:
• twice daily, orally;
• with meals to reduce the likelihood of stomach upset.
• To control blood sugar levels, your doctor may increase the dose of this medicine.
• If you have impaired kidney function, your doctor may prescribe a lower dose.

While taking this medicine, continue to follow the diet recommended by your doctor and pay attention to
consuming carbohydrates evenly throughout the day.
It is unlikely that taking this medicine alone will lead to abnormally low blood sugar levels (hypoglycaemia).
Low blood sugar may occur when this medicine is taken together with a sulphonylurea derivative or insulin – in such cases, your doctor
may reduce the dose of the sulphonylurea derivative or insulin.
The break line on the tablet is not intended for splitting the tablet.
Taking more Combodiab than prescribed
If you take more than the prescribed amount of this medicine, contact your doctor immediately.
Go to hospital if symptoms of lactic acidosis occur, such as feeling cold or unwell, severe nausea or vomiting, stomach pain, unexplained weight loss, muscle cramps or rapid breathing (see section “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 Combodiab
To maintain control of blood sugar levels, take this medicine for as long as your doctor recommends. Do not stop taking this medicine without consulting your doctor first. Discontinuing Combodiab may cause blood sugar levels to rise.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
You should STOP taking Combodiab and immediately contact your doctor if any of the following serious adverse effects occur:

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

Combodiab may very rarely (may occur in up to 1 in 10,000 patients) cause a very serious adverse effect known as lactic acidosis (see section "Warnings and precautions"). If a patient develops lactic acidosis, stop taking Combodiab immediately and seek immediate medical attention from a doctor or the nearest hospital, as lactic acidosis may lead to coma.

In the event of a severe allergic reaction (frequency not known), including rash, hives, skin blisters or skin peeling, and swelling of the face, lips, tongue, or throat, which may cause difficulty in breathing or swallowing, treatment with this medicine must be discontinued and immediate medical advice sought. Your doctor may prescribe medication to treat the allergic reaction and may switch you to another medicine (change of medicine) for the treatment of diabetes.

In some patients taking metformin, the following adverse effects occurred after starting treatment with sitagliptin:

• 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, diarrhoea, constipation, drowsiness

Some patients experienced diarrhoea, nausea, bloating, constipation, stomach pain, or vomiting after starting treatment with sitagliptin in combination with metformin (common).

In some patients taking this medicine together with a sulfonylurea derivative, such as glimepiride, the following adverse effects occurred:

• Very common (may affect more than 1 in 10 people): low blood sugar levels
• Common: constipation

In some patients taking this medicine in combination with pioglitazone, the following adverse effects occurred:

• Common: swelling of hands or feet

In some patients taking this medicine in combination with insulin, the following adverse effects occurred:

• Very common: low blood sugar levels
• Uncommon: dry mouth, headache

In clinical trials, the following adverse effects occurred in some patients taking sitagliptin alone (one of the active substances in Combodiab), or after marketing when taking Combodiab alone, sitagliptin alone, or in combination with other antidiabetic medicines:

• Common: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose and sore throat, bone and joint pain, pain in arms or legs
• Uncommon: dizziness, constipation, itching
• Rare (may affect up to 1 in 1,000 people): decreased platelet count
• Frequency not known: kidney disorders (sometimes requiring dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of blistering skin condition)

In some patients taking metformin alone, the following adverse effects occurred:

• Very common: nausea, vomiting, diarrhoea, stomach pain, and loss of appetite. These symptoms may occur when starting metformin and usually resolve over time.
• Common: metallic taste, reduced or low blood levels of vitamin B12 (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling or numbness (paresthesia), or paleness or yellowing of the skin). Your doctor may order certain tests to determine the cause of symptoms, as some of them may also be caused by diabetes or other unrelated health problems.
• Very rare: hepatitis (liver disease), urticaria, skin redness (rash), or itching

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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. Adverse effects can also be reported to the responsible entity. Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Combodiab

Keep this medicine out of 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 stated month.
Store below 30°C.
Medicines must 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 hydrochloride 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 additionally 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 brown, elongated, oval film-coated tablets with a division line between "S" and "B" on one side and a division line on the other side.
Tablet diameter: 21.3 mm ± 0.5 mm.
The pack contains 56 film-coated tablets in a blister made of PVC/PVDC/Aluminium, packed in a cardboard outer container.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
BIOTON S.A.
ul. Starościńska 5
02-516 Warszawa
Poland

Manufacturers
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 further information about this medicinal product, please contact:
BIOTON S.A.
02-516 Warszawa
ul. Starościńska 5
Tel: +48 (22) 721 40 00
[email protected]

This medicinal product is authorised in the European Economic Area under the following names:
Malta: COMBODIAB 50mg/1000 mg film-coated tablets
Poland: COMBODIAB