Karbicombi

Leaflet accompanying the packaging: information for the user

Karbicombi, 8 mg + 12.5 mg, tablets

Karbicombi, 16 mg + 12.5 mg, tablets

Karbicombi, 32 mg + 12.5 mg, tablets

Karbicombi, 32 mg + 25 mg, tablets

candesartan cilexetil + hydrochlorothiazide

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

• The leaflet should be kept, so it can be re-read if necessary.
• In case of any doubts, the patient should consult a doctor or pharmacist.
• This medication has been prescribed to a specific person. It should not be given to others. The medication 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 or pharmacist. 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 medication contains two active substances: candesartan cilexetil and hydrochlorothiazide. These substances work together to lower blood pressure.
Candesartan cilexetil belongs to a group of medications called angiotensin II receptor antagonists. It causes blood vessels to relax and dilate, which helps to lower blood pressure.
Hydrochlorothiazide belongs to a group of medications called diuretics. It helps the body get rid of excess water and salt, such as sodium, in the urine. This helps to lower blood pressure.
The doctor may prescribe Karbicombi if blood pressure is not adequately controlled when taking 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 medication (listed in section 6);
• if the patient is allergic to sulfonamide medications. In case of doubt, the patient should consult a doctor;
• after the third month of pregnancy (it is also recommended to avoid taking Karbicombi in early pregnancy - see the 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 a long-standing low potassium level in the blood;
• if the patient has a long-standing high calcium level 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 medication 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 the following 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 had severe vomiting or has diarrhea;
• if the patient has a condition called Conn's syndrome (primary hyperaldosteronism);
• if the patient has ever had a condition 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 to become pregnant. Karbicombi should not be taken during pregnancy, and the doctor will recommend an alternative medication;
• if the patient is taking any of the following medications for high blood pressure:
• ACE inhibitors (e.g., enalapril, lisinopril, ramipril, etc.), especially if the patient has kidney problems related to diabetes,
• aliskiren.

The doctor may monitor the patient's kidney function, blood pressure, and electrolyte levels (e.g., 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 conditions, 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 that they are taking Karbicombi. Karbicombi may cause excessive lowering of blood pressure when used in combination with certain anesthetics.

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 medications

The patient should inform their doctor or pharmacist about all medications they are currently taking or have recently taken, as well as any medications they plan to take.
Karbicombi may affect the action of other medications, and other medications may affect the action of Karbicombi. In the case of certain medications, the doctor may recommend periodic blood tests.
In particular, the patient should inform their doctor about taking any of the following medications, as the doctor may need to change the dose and/or take other precautions:

• other blood pressure-lowering medications, including beta-blockers, medications containing aliskiren, diazoxide, and ACE inhibitors, such as enalapril, captopril, lisinopril, or ramipril;
• non-steroidal anti-inflammatory medications (NSAIDs), such as ibuprofen, naproxen, diclofenac, celecoxib, or etoricoxib (medications that relieve pain and inflammation);
• aspirin (in doses above 3 g per day) (medication that relieves pain and inflammation);
• potassium supplements or salt substitutes containing potassium (medications that increase potassium levels in the blood);
• calcium supplements or vitamin D;
• medications that lower cholesterol, such as colestyramine or colestipol;
• anti-diabetic medications (tablets or insulin);
• medications that control heart rhythm (anti-arrhythmic medications), such as digoxin and beta-blockers;
• medications whose action may be affected by potassium levels in the blood, such as certain antipsychotic medications;
• heparin (a blood thinner);
• diuretics (medications that increase urine production);
• laxatives;
• penicillin or cotrimoxazole (also known as trimethoprim/sulfamethoxazole) (antibiotics);
• amphotericin (a medication used to treat fungal infections);
• lithium (a medication used to treat mental disorders);
• corticosteroids, such as prednisolone;
• adrenocorticotropic hormone (ACTH);
• anti-cancer medications;
• amantadine (a medication used to treat Parkinson's disease or severe viral infections);
• barbiturates (a type of sedative, also used to treat epilepsy);
• carbenoxolone (a medication used to treat esophageal or mouth ulcers);
• anticholinergic medications, such as atropine and bipiperiden;
• cyclosporine, a medication used to prevent organ rejection;
• other medications that may enhance the blood pressure-lowering effect of Karbicombi, such as baclofen (a medication that reduces muscle tension), amifostine (an anti-cancer medication), and certain antipsychotic medications;
• 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 to become pregnant. The doctor will usually recommend stopping Karbicombi before planned pregnancy or as soon as pregnancy is confirmed and recommend an alternative medication. Karbicombi should not be taken during pregnancy, and it is not recommended to take it in early pregnancy and it should not be taken after the third month of pregnancy, as it may seriously harm the fetus.
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 an alternative medication during breastfeeding.

Driving and operating machinery

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

3. How to take Karbicombi

This medication should always be taken as recommended by the doctor. In case of doubt, the patient should consult their doctor or pharmacist.
It is essential to take Karbicombi every day.
The recommended dose of Karbicombi is usually one tablet per day.
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 medication.

Taking a higher dose of Karbicombi than recommended

In case of taking a higher dose of Karbicombi than recommended, the patient 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 Karbicombi treatment

Stopping Karbicombi treatment 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 medication, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medications, 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 are caused by hydrochlorothiazide.

The patient should stop taking Karbicombi and seek immediate medical attention 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 hives).

Karbicombi may cause a decrease in the number of white blood cells, which may be associated with a decreased resistance 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 feeling of tingling 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, urticaria, sun-induced 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.
• Numbness or tingling of the upper or lower limbs.
• Transient blurred vision.
• Heart rhythm disturbances.
• Breathing difficulties (including pneumonia and fluid 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 skin rash, which develops rapidly, with blistering or peeling of the skin and possible blistering in the mouth.

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):

• Malignant skin tumors and lip tumors (non-melanoma skin tumors).
• Diarrhea.
• Sudden short-sightedness.
• Blurred vision or eye pain due to increased pressure (possible symptoms of fluid accumulation in the vascular layer surrounding the eye - excessive accumulation of fluid 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 darkening, blisters, peeling, and nodules on the skin).

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or pharmacist. 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
Phone: +48 22 49 21 301
Fax: +48 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 the medication.

5. How to store Karbicombi

The medication should be stored out of sight and reach of children.
The medication should not be used after the expiration date stated on the packaging. The expiration date refers to the last day of the specified month.
PVC/PVDC/Aluminum blister:
The medication should not be stored at temperatures above 30°C.
OPA/Aluminum/PVC/Aluminum blister:
There are no special storage recommendations.
Medications should not be disposed of in wastewater or household waste. The patient should ask their pharmacist how to dispose of medications 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 8 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. Each tablet contains 16 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. Each tablet contains 32 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. Each tablet contains 32 mg of candesartan cilexetil and 25 mg of hydrochlorothiazide.
• Other ingredients are: lactose monohydrate, cornstarch, macrogol 8000, hydroxypropylcellulose, calcium carmellose, magnesium stearate, red iron oxide (E 172) - only in 16 mg + 12.5 mg and 32 mg + 25 mg tablets, yellow iron oxide (E 172) - only in 32 mg + 12.5 mg tablets. See section 2: "Karbicombi contains lactose".

What Karbicombi looks like and contents of the packaging

Karbicombi, 8 mg + 12.5 mg, tablets: white, biconvex, oval tablets, with a score line on one side. The score line on the tablet is only to facilitate breaking and not to divide into equal doses.
Karbicombi, 16 mg + 12.5 mg, tablets: light pink, biconvex, oval tablets, with a score line on one side. The score line on the tablet is only to facilitate breaking and not to divide into equal doses.
Karbicombi, 32 mg + 12.5 mg, tablets: yellowish-white, biconvex, oval tablets, with a score line on one side. The score line on the tablet is only to facilitate breaking and not to divide into equal doses.
Karbicombi, 32 mg + 25 mg, tablets: light pink, biconvex, oval tablets, with a score line on one side. The tablet can be divided into equal doses.
Packaging: 28, 56, or 84 (only for 8 mg + 12.5 mg and 16 mg + 12.5 mg) tablets in blisters, in a cardboard box

Marketing authorization holder

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

This medication is authorized for use in the Member States of the European Economic Area under the following names:

Date of last revision of the leaflet:17.02.2022