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 to 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 salts, 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 prolonged low potassium level in the blood;
• if the patient has a prolonged 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 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 adrenal gland disorder called Conn's syndrome (or 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 are pregnant or planning to become pregnant. Karbicombi should not be taken during pregnancy, especially after the third month, as it may harm the fetus (see the 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 patient should protect their skin 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 experiences 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 within 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 condition.
• if the patient is taking any of the following medications for high blood pressure:
• ACE inhibitors (such as enalapril, lisinopril, ramipril, etc.), especially if the patient has diabetes-related kidney problems;
• aliskiren.

The doctor may monitor the patient's 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:" and "Warnings and precautions".
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 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 patient group.

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 medications for high blood pressure, 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 for pain and inflammation);
• aspirin (in doses over 3 g per day) (medication for pain and inflammation);
• potassium supplements or salt substitutes containing potassium (medications that increase potassium levels in the blood);
• calcium supplements or vitamin D;
• medications for lowering cholesterol, such as colestyramine or colestipol;
• anti-diabetic medications (tablets or insulin);
• medications for controlling heart rhythm (anti-arrhythmic medications), such as digoxin and beta-blockers;
• medications that may affect potassium levels in the blood, such as certain antipsychotic medications;
• heparin (blood thinner);
• diuretics (diuretic medications);
• laxatives;
• penicillin or cotrimoxazole (also known as trimethoprim/sulfamethoxazole) (antibiotics);
• amphotericin (medication for fungal infections);
• lithium (medication for mental disorders);
• steroids, such as prednisolone;
• adrenocorticotropic hormone (ACTH);
• anti-cancer medications;
• amantadine (medication for Parkinson's disease or severe viral infections);
• barbiturates (type of sedative medication, also used to treat epilepsy);
• carbenoxolone (medication for esophageal disease or mouth ulcers);
• anticholinergic medications, such as atropine and bipiperidine;
• cyclosporine, a medication used to prevent organ rejection;
• other medications that may enhance the blood pressure-lowering effect, such as baclofen (medication for muscle relaxation), amifostine (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 the possibility of consuming alcohol with their doctor, 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 taking a different medication instead of Karbicombi. Karbicombi should not be taken during pregnancy, especially after the third month, as it may harm the fetus.
Breastfeeding
The patient should inform their doctor if they are breastfeeding or plan to breastfeed. Karbicombi should not be taken during breastfeeding. The doctor may recommend taking a different medication during breastfeeding.

Driving and operating machinery

Some patients may experience fatigue or dizziness while taking Karbicombi. If these 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 directed 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 to help remember to take the medication.

Taking a higher dose of Karbicombi than recommended

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

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 everyone will experience them.
It is essential for the patient to know which 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 skin itching (with hives).

Karbicombi may cause a decrease in the number of white blood cells, which can be associated with 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 occur in up to 1 in 10 patients):

• 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 patients with existing kidney disease or heart failure. In case of significant changes, fatigue, weakness, heart rhythm disturbances, or 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 occur in up to 1 in 100 patients):

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

Rare (may occur in up to 1 in 1,000 patients):

• Jaundice (yellowing of the skin or eyes). If such symptoms occur, the patient should contact their doctor immediately.
• Affecting kidney function, especially in patients 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 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 skin rash, which develops rapidly, with blistering or peeling of the skin and possible blistering in the mouth.

Very rare (may occur in up to 1 in 10,000 patients):

• 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 available data):

• Malignant skin tumors and lip tumors (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 (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 the 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.
Reporting side effects will help gather more information 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 taken 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 precautions.
Medications should not be disposed of in wastewater or household waste. The patient should ask their pharmacist how to dispose of unused medications. 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 dividing line on one side. The dividing line on the tablet is only to facilitate breaking and does not divide the tablet into equal doses.
Karbicombi, 16 mg + 12.5 mg, tablets: light pink, biconvex, oval tablets, with a dividing line on one side. The dividing line on the tablet is only to facilitate breaking and does not divide the tablet into equal doses.
Karbicombi, 32 mg + 12.5 mg, tablets: yellowish-white, biconvex, oval tablets, with a dividing line on one side. The dividing line on the tablet is only to facilitate breaking and does not divide the tablet into equal doses.
Karbicombi, 32 mg + 25 mg, tablets: light pink, biconvex, oval tablets, with a dividing 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 doses) 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 marketing in the Member States of the European Economic Area under the following names:

Date of last revision of the leaflet:17.02.2022