Karbicombi

Leaflet attached to 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

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• In case of any doubts, you should consult a doctor or pharmacist.
• 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 tell 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 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 blood vessels to relax and dilate, 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.
Your doctor may prescribe Karbicombi if your blood pressure is not adequately controlled with candesartan cilexetil or hydrochlorothiazide alone.

2. Important information before taking Karbicombi

When not to take Karbicombi:

• if you are allergic to candesartan cilexetil or hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to sulfonamide medicines. If in doubt, consult your doctor;
• after the third month of pregnancy (it is also recommended to avoid taking Karbicombi in early pregnancy - see section "Pregnancy and breastfeeding");
• if you have severe kidney disease;
• if you have severe liver disease or bile duct obstruction (disorders of bile flow from the gallbladder);
• if you have a long-standing low potassium level in the blood;
• if you have a long-standing high calcium level in the blood;
• if you have ever had gout;
• if you have diabetes or kidney problems and are taking a blood pressure-lowering medicine containing aliskiren.

If in doubt whether any of the above situations apply to you, you should consult your doctor or pharmacist before taking Karbicombi.

Warnings and precautions

Before starting to take Karbicombi, you should discuss it with your doctor or pharmacist:

• if you have diabetes;
• if you have heart, liver, or kidney disease;
• if you have recently had a kidney transplant;
• if you have had severe vomiting or have diarrhea;
• if you have a disease of the adrenal glands called Conn's syndrome (or primary hyperaldosteronism);
• if you have ever had a disease called systemic lupus erythematosus;
• if you have low blood pressure;
• if you have ever had a stroke;
• if you have ever had an allergy or asthma;
• you should inform your doctor if you are planning to become pregnant (or think you may be pregnant). Karbicombi should not be taken during pregnancy, and your doctor will normally advise you to take a different medicine instead of Karbicombi. Karbicombi should not be taken during the first trimester of pregnancy, and it should not be taken after the third month of pregnancy, as it may seriously harm the baby (see section "Pregnancy and breastfeeding");
• if you have had skin cancer or if an unexpected skin change occurs during treatment. Treatment with hydrochlorothiazide, especially at 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, you should protect your skin from sunlight and UV radiation;
• if you have had breathing or lung problems after taking hydrochlorothiazide (including pneumonia or fluid accumulation in the lungs). If you experience severe shortness of breath or difficulty breathing after taking Karbicombi, you should seek medical attention immediately;
• if you have blurred vision 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 can occur within a few hours to weeks after taking Karbicombi. If left untreated, they can lead to permanent vision loss. If you have previously been allergic to penicillin or sulfonamides, you may be more prone to developing this condition;
• if you are taking any of the following medicines for high blood pressure:
• ACE inhibitors (such as enalapril, lisinopril, ramipril, etc.), especially if you have kidney problems related to diabetes,
• aliskiren.

Your doctor may monitor your kidney function, blood pressure, and electrolyte levels (such as potassium) in your blood at regular intervals.
See also the information under the heading "When not to take Karbicombi:" and "Warnings and precautions".
If you have any of the above conditions, your doctor may advise you to have more frequent check-ups and diagnostic tests.
If you are planning to have surgery, you should tell your doctor or dentist that you 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 patient group.

Karbicombi and other medicines

You should tell your doctor or pharmacist about all the medicines you are taking now or have taken recently, as well as any medicines you plan to take.
Karbicombi may affect the action of other medicines, and other medicines may affect the action of Karbicombi. In the case of certain medicines, your doctor may recommend periodic blood tests.
In particular, you should inform your doctor if you are taking any of the following medicines, as your 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 medicines (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);
• heart rhythm-regulating medicines (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);
• diuretics (water tablets);
• 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 or mouth ulcers);
• anticholinergic medicines, such as atropine and bipiperiden;
• 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 you are 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, you should discuss with your doctor the possibility of consuming alcohol, as alcohol may cause dizziness or fainting.

Pregnancy and breastfeeding

Pregnancy
You should inform your doctor if you are planning to become pregnant (or think you may be pregnant). Your doctor will normally advise you to stop taking Karbicombi before a planned pregnancy or as soon as possible after confirmation of pregnancy, and will advise you to take a different medicine instead of Karbicombi. Karbicombi should not be taken during the first trimester of pregnancy, and it should not be taken after the third month of pregnancy, as it may seriously harm the baby.
Breastfeeding
You should inform your doctor if you are breastfeeding or plan to breastfeed. Karbicombi should not be taken during breastfeeding. Your doctor may advise you to take a different medicine while breastfeeding.

Driving and using machines

Some patients taking Karbicombi may experience fatigue or dizziness. If these occur, you should not drive, use tools, or operate machinery.
Karbicombi contains lactose, a type of sugar.
If you have been told that you have an intolerance to some sugars, you should consult your doctor before taking Karbicombi.

3. How to take Karbicombi

This medicine should always be taken exactly as your doctor has told you. If you are not sure, you should ask your doctor or pharmacist.
It is important to take Karbicombi every day.
The recommended dose of Karbicombi is one tablet once daily.
The tablet should be swallowed with water.
You should try to take the tablet at the same time every day, as this will help you remember to take your medicine.

Taking a higher dose of Karbicombi than recommended

If you have taken more Karbicombi than you should, you should contact your doctor or pharmacist immediately.

Missing a dose of Karbicombi

You should not take a double dose to make up for a forgotten dose.
You should take the next dose of Karbicombi at the usual time.

Stopping treatment with Karbicombi

Stopping treatment with Karbicombi may cause your blood pressure to rise again. Therefore, you should not stop taking Karbicombi without consulting your doctor.
If you have any further questions on the use of this medicine, you should ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Karbicombi can cause side effects, although not everybody gets them.
It is important that you know what side effects may occur with Karbicombi. Some side effects of Karbicombi are caused by candesartan cilexetil, and some are caused by hydrochlorothiazide.

You should stop taking Karbicombi and seek medical help immediately if you 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 ability to fight infections and may cause fatigue, infection, or fever. If you experience such symptoms, you should tell your doctor. Your doctor may recommend periodic blood tests to check if Karbicombi is affecting your blood (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. If this decrease is significant, it may cause weakness, fatigue, or muscle cramps.
• Increased or decreased potassium levels in the blood, especially in people with existing kidney disease or heart failure. If these changes are significant, they may cause fatigue, weakness, heart rhythm disturbances, or a tingling sensation.
• 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, photosensitivity reaction.

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

• Jaundice (yellowing of the skin or eyes). If you experience such symptoms, you should contact your doctor immediately.
• Affecting kidney function, especially in people with existing kidney disease or heart failure.
• Sleep disturbances, depression, anxiety.
• Numbness or tingling 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. This may cause fatigue, infection, fever, or easy bruising.
• Severe skin rash, which develops quickly, 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 hepatitis. This may cause fatigue, yellowing of the skin and eyes, and flu-like symptoms.
• 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 cancer and lip cancer (non-melanoma skin cancer).
• 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 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 darkening, blisters, peeling, and nodules on the skin).

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your 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:
Jerozolimskie Avenue 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, you can help provide more information on the safety of this medicine.

5. How to store Karbicombi

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
PVC/PVDC/Aluminum blister:
Do not store above 30°C.
OPA/Aluminum/PVC/Aluminum blister:
No special storage precautions.

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.
• The other ingredients are: lactose monohydrate, cornstarch, macrogol 8000, hydroxypropylcellulose, calcium carmellose, magnesium stearate, iron oxide red (E 172) - only in 16 mg + 12.5 mg and 32 mg + 25 mg tablets, iron oxide yellow (E 172) - only in 32 mg + 12.5 mg tablets. See section 2: "Karbicombi contains lactose".

What Karbicombi looks like and contents of the pack

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: pale 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: pale 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) 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 medicine 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