Karbicombi

Leaflet accompanying the packaging: information for the user

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

Karbicombi (Candesartan/HCT Krka)

32 mg + 25 mg, tablets
Candesartan cilexetil + Hydrochlorothiazide
Karbicombi and Candesartan/HCT Krka are different trade names for the same medicine.

It is essential to carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• The leaflet should be kept so that it can be re-read if necessary.
• In case of any doubts, the doctor or pharmacist should be consulted.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1 What is Karbicombi and what is it used for

Karbicombi is used to treat high blood pressure (hypertension) in adult patients. This medicine contains two active substances: candesartan cilexetil and hydrochlorothiazide. These substances together lower blood pressure.
Candesartan cilexetil belongs to a group of medicines called angiotensin II receptor antagonists.
It causes relaxation and widening of blood vessels, which helps to lower blood pressure.
Hydrochlorothiazide belongs to a group of medicines called diuretics. It helps the body get rid of excess water and salts, such as sodium, in the urine. This helps to lower blood pressure.
The doctor may prescribe Karbicombi if blood pressure is not sufficiently controlled when using only candesartan cilexetil or only hydrochlorothiazide.

2. Important information before taking Karbicombi

When not to take Karbicombi:

• if the patient is allergic to candesartan cilexetil or hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6);
• if the patient is allergic to sulfonamide medicines. In case of doubt, consult a doctor;
• after the third month of pregnancy (it is also recommended to avoid taking Karbicombi in early pregnancy - see section "Pregnancy and breastfeeding");
• if the patient has severe kidney disease;
• if the patient has severe liver disease or bile duct obstruction

(disorders of bile flow from the gallbladder);

• if the patient has persistently low potassium levels in the blood;
• if the patient has persistently high calcium levels in the blood;
• if the patient has ever had gout;
• if the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren.

In case of doubt whether any of the above situations apply to the patient, they should consult a doctor or pharmacist before taking Karbicombi.

Warnings and precautions

Before starting to take Karbicombi, the patient should discuss it with their doctor or pharmacist:

• if the patient has diabetes;
• if the patient has heart, liver, or kidney disease;
• if the patient has recently had a kidney transplant;
• if the patient has severe vomiting or diarrhea;
• if the patient has a disease of the adrenal glands called Conn's syndrome (or primary hyperaldosteronism);
• if the patient has ever had a disease called systemic lupus erythematosus;
• if the patient has low blood pressure;
• if the patient has ever had a stroke;
• if the patient has ever had an allergy or asthma;
• the patient should inform their doctor if they suspect (or plan) pregnancy. Karbicombi should not be taken in early pregnancy and should not be taken after the third month of pregnancy, as it may seriously harm the baby (see section "Pregnancy and breastfeeding");
• if the patient has a history of skin cancer or if an unexpected skin change occurs during treatment. Treatment with hydrochlorothiazide, especially in high doses and for a long time, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). During treatment with Karbicombi, the skin should be protected from sunlight and UV radiation;
• if the patient has a history of breathing or lung problems (including pneumonia or fluid accumulation in the lungs) after taking hydrochlorothiazide. If the patient experiences severe shortness of breath or difficulty breathing after taking Karbicombi, they should seek medical help immediately;
• if the patient has vision loss or eye pain. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive fluid accumulation between the choroid and sclera) or increased pressure inside the eye - they may occur within a few hours to weeks after taking Karbicombi. If left untreated, they can lead to permanent vision loss. If the patient has previously been allergic to penicillin or sulfonamides, they may be more prone to developing this disease;
• if the patient is taking any of the following medicines for high blood pressure:
• ACE inhibitors (such as enalapril, lisinopril, ramipril, etc.), especially if the patient has kidney problems related to diabetes,
• aliskiren.

The doctor may monitor kidney function, blood pressure, and electrolyte levels (such as potassium) in the blood at regular intervals.
See also the information under the heading "When not to take Karbicombi".
If the patient has any of the above diseases, the doctor may recommend more frequent check-ups and diagnostic tests.
If the patient is scheduled to undergo surgery, they should inform their doctor or dentist about taking Karbicombi. Karbicombi may cause excessive lowering of blood pressure when used in combination with certain anesthetics.
Karbicombi may cause increased sensitivity of the skin to sunlight.

Children and adolescents

There is no experience with the use of Karbicombi in children (under 18 years of age), so it should not be used in this group of patients.

Karbicombi and other medicines

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.
Karbicombi may affect the action of other medicines, and other medicines may affect the action of Karbicombi. In the case of taking certain medicines, the doctor may recommend periodic blood tests.
In particular, the patient should inform their doctor about taking any of the following medicines, as the doctor may need to change the dose and/or take other precautions:

• other blood pressure-lowering medicines, including beta-blockers, aliskiren, diazoxide, and ACE inhibitors, such as enalapril, captopril, lisinopril, or ramipril;
• non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, diclofenac, celecoxib, or etoricoxib (pain-relieving and anti-inflammatory medicines).
• aspirin (in doses over 3 g per day) (pain-relieving and anti-inflammatory medicine);
• potassium supplements or salt substitutes containing potassium (medicines that increase potassium levels in the blood);
• calcium supplements or vitamin D;
• cholesterol-lowering medicines, such as colestyramine or colestipol;
• anti-diabetic medicines (tablets or insulin);
• medicines that control heart rhythm (anti-arrhythmic medicines), such as digoxin and beta-blockers;
• medicines whose action may be affected by potassium levels in the blood, such as certain antipsychotic medicines;
• heparin (a blood-thinning medicine);
• diuretic medicines;
• laxatives;
• penicillin or cotrimoxazole (also known as trimethoprim/sulfamethoxazole) (antibiotics);
• amphotericin (a medicine used to treat fungal infections);
• lithium (a medicine used to treat mental disorders);
• corticosteroids, such as prednisolone;
• adrenocorticotropic hormone (ACTH);
• anti-cancer medicines;
• amantadine (a medicine used to treat Parkinson's disease or severe viral infections);
• barbiturates (a type of sedative, also used to treat epilepsy);
• carbenoxolone (a medicine used to treat esophageal disease or mouth ulcers);
• anticholinergic medicines, such as atropine and bipiperidine;
• cyclosporine, a medicine used to prevent organ rejection;
• other medicines that may enhance the blood pressure-lowering effect, such as baclofen (a muscle relaxant), amifostine (an anti-cancer medicine), and certain antipsychotic medicines.
• if the patient is taking an ACE inhibitor or aliskiren (see also the information under the heading "When not to take Karbicombi" and "Warnings and precautions").

Karbicombi with food, drink, and alcohol

• Karbicombi can be taken with or without food.
• Before taking Karbicombi, the patient should discuss with their doctor the possibility of consuming alcohol, as alcohol may cause dizziness or fainting.

Pregnancy and breastfeeding

Pregnancy
The patient should inform their doctor if they suspect (or plan) pregnancy. The doctor will usually recommend stopping Karbicombi before planned pregnancy or immediately after confirming pregnancy and recommend taking a different medicine instead of Karbicombi. Karbicombi should not be taken in early pregnancy and should not be taken after the third month of pregnancy, as it may seriously harm the baby.
Breastfeeding
The patient should inform their doctor if they are breastfeeding or plan to breastfeed. Karbicombi is not recommended during breastfeeding. The doctor may recommend taking a different medicine during breastfeeding.

Driving and using machines

Some patients may experience fatigue or dizziness while taking Karbicombi. If these occur, the patient should not drive vehicles, use tools, or operate machines.
Karbicombi contains lactose monohydrate,a type of sugar.
If the patient has been informed that they have intolerance to some sugars, they should consult their doctor before taking Karbicombi.

3. How to take Karbicombi

This medicine should always be taken exactly as prescribed by the doctor. In case of doubt, the patient should consult their doctor or pharmacist.
Karbicombi is available in the following strengths: 8 mg + 12.5 mg; 16 mg + 12.5 mg; 32 mg + 12.5 mg; and 32 mg + 25 mg.
It is essential to take Karbicombi every day.
The recommended dose of Karbicombi is one tablet once daily.
The tablet should be swallowed with water.
The patient should try to take the tablet at the same time every day, which will help them remember to take the medicine.

Taking a higher dose of Karbicombi than recommended

If the patient takes a higher dose of Karbicombi than recommended, they should immediately contact their doctor or pharmacist.

Missing a dose of Karbicombi

The patient should not take a double dose to make up for a missed dose.
The patient should take the next dose of Karbicombi at the usual time.

Stopping treatment with Karbicombi

Stopping treatment with Karbicombi may cause blood pressure to rise again. Therefore, the patient should not stop taking Karbicombi without consulting their doctor.
In case of any further doubts about taking this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Karbicombi can cause side effects, although not everybody gets them.
It is essential for the patient to know what side effects may occur. Some side effects of Karbicombi are caused by candesartan cilexetil, and some by hydrochlorothiazide.

The patient should stop taking Karbicombi and seek medical help immediately if they experience any of the following allergic reactions:

• difficulty breathing with or without swelling of the face, lips, tongue, and/or throat,
• swelling of the face, lips, tongue, and/or throat, which may cause difficulty swallowing,
• severe itching of the skin (with lumps).

Karbicombi may cause a decrease in the number of white blood cells, which can be associated with decreased immunity to infections and the occurrence of fatigue, infection, or fever. If such symptoms occur, the patient should inform their doctor. The doctor may recommend periodic blood tests to check if Karbicombi affects the blood count (agranulocytosis).
Other possible side effects include:

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

• Changes in blood test results:
• Decreased sodium levels in the blood. In case of significant decrease, weakness, fatigue, or muscle cramps may occur.
• Increased or decreased potassium levels in the blood, especially in people with existing kidney disease or heart failure. In case of significant changes, fatigue, weakness, heart rhythm disturbances, or a tingling sensation may occur.
• Increased cholesterol, sugar, or uric acid levels in the blood.
• Presence of sugar in the urine.
• Dizziness/spinning sensation or weakness.
• Headache.
• Respiratory tract infection.

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

• Low blood pressure. This may cause fainting or dizziness.
• Lack of appetite, diarrhea, constipation, stomach upset.
• Skin rash, hives, sun-related skin rash.

Rare (may affect up to 1 in 1,000 people):

• Jaundice (yellowing of the skin or eyes). If such symptoms occur, the patient should immediately contact their doctor.
• Affecting kidney function, especially in people with existing kidney disease or heart failure.
• Sleep disturbances, depression, anxiety.
• Tingling or prickling sensation in the arms or legs.
• Temporary blurred vision.
• Heart rhythm disturbances.
• Breathing difficulties (including pneumonia and fluid accumulation in the lungs).
• High fever (fever).
• Pancreatitis, causing moderate or severe abdominal pain.
• Muscle cramps.
• Vascular damage causing red or purple spots on the skin.
• Decreased number of red or white blood cells or platelets. Fatigue, infection, fever, or easy bruising may occur.
• Severe rash, which develops rapidly, with blistering or peeling of the skin and possible blistering in the mouth.

and/or throat.

Very rare (may affect up to 1 in 10,000 people):

• Swelling of the face, lips, tongue, and/or throat.
• Itching.
• Back pain, joint pain, and muscle pain.
• Changes in liver function, including liver inflammation. Fatigue, yellowing of the skin and eyes, and flu-like symptoms may occur.
• Cough.
• Nausea.
• Acute respiratory failure (symptoms include severe shortness of breath, fever, weakness, and confusion).

Unknown frequency (cannot be estimated from the available data):

• Skin and lip cancer (non-melanoma skin cancer).
• Diarrhea.
• Sudden short-sightedness.
• Vision loss or eye pain due to increased pressure (possible symptoms of fluid accumulation in the vascular layer surrounding the eye - excessive fluid accumulation between the choroid and sclera - or acute angle-closure glaucoma).
• Systemic lupus erythematosus and cutaneous lupus (an allergic reaction with accompanying fever, joint pain, skin rash, including discoloration, blisters, peeling, and lumps on the skin).

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Aleje Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Karbicombi

The medicine should be stored out of sight and reach of children.
The medicine should not be used after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
PVC/PVDC/Aluminum blisters: Do not store above 30°C.
OPA/Aluminum/PVC/Aluminum blisters: No special storage precautions.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Karbicombi contains

• The active substances of Karbicombi are candesartan cilexetil and hydrochlorothiazide. Each tablet contains 32 mg of candesartan cilexetil and 25 mg of hydrochlorothiazide.
• The other ingredients are: lactose monohydrate, cornstarch, hydroxypropylcellulose, magnesium stearate, calcium carmellose, macrogol 8000, red iron oxide (E 172).

What Karbicombi looks like and contents of the pack

Pale pink, biconvex, oval tablets, with a score line on one side. The tablet can be divided into equal doses.
Packaging: 30 or 60 tablets in PVC/PVDC/Aluminum or OPA/Aluminum/PVC/Aluminum blisters, in a cardboard box.
For more detailed information, the patient should contact the marketing authorization holder or parallel importer.

Marketing authorization holder in Austria, the country of export:

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer:

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

Parallel importer:

Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Austrian marketing authorization number: 1-30800

Parallel import authorization number: 114/20

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

Austria
Candesartan/HCT Krka
Bulgaria, Poland, Romania, Slovakia
Karbicombi
Czech Republic
Cancombino
Germany
Candesartan-HCTad
Greece
Candesartan+HCTZ/Krka
Cyprus
Candesartan/Hydrochlorothiazide KRKA
Ireland
Candesartan Hydrochlorothiazide Krka
Slovenia
Candecombi
Lithuania
Canocombi

Date of approval of the leaflet: 06.05.2025

[Information about the trademark]