Karbicombi

Package leaflet: Information for the user

Warning! Keep the leaflet. Information on the immediate packaging in a foreign language.
Karbicombi (Candesartan e Idroclorotiazide HCS)
32 mg + 12.5 mg, tablets
Candesartanum cilexetili + Hydrochlorothiazidum
Karbicombi and Candesartan e Idroclorotiazide HCS are different trade names of the same
medicinal product.
Please read this leaflet carefully before using the 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 or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Table of contents of the leaflet

1. What Karbicombi is and what it is 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 pack and other information

1 What Karbicombi is and what it is 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, thus helping to reduce blood pressure.
Hydrochlorothiazide belongs to a group of medicines called diuretics (water pills). It helps the body eliminate water and salts, such as sodium salts, through urine. This helps lower blood pressure.
Your doctor may prescribe Karbicombi if your blood pressure is not sufficiently controlled with candesartan cilexetil alone or hydrochlorothiazide alone.

2 Important information before taking Karbicombi

When not to take Karbicombi:

• if you are allergic to candesartan cilexetil or hydrochlorothiazide, or to 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 3rd month of pregnancy (it is also better to avoid using Karbicombi in early pregnancy - see section "Pregnancy and breastfeeding");
• if you have severe kidney disease;
• if you have severe liver disease or biliary obstruction (impaired bile flow from the gallbladder);
• if you have persistently low potassium levels in the blood;
• if you have persistently high calcium levels in the blood;
• if you have ever had gout;
• if you have diabetes or kidney problems and are being treated with a blood pressure-lowering medicine containing aliskiren.

If you are unsure whether any of the above situations apply to you, contact your doctor or pharmacist before taking Karbicombi.
Warnings and precautions
Before starting Karbicombi, discuss with your doctor or pharmacist:

• if you have diabetes;
• if you have heart, liver or kidney disease;
• if you have recently received a kidney transplant;
• if you have severe vomiting or diarrhea, either currently or in the past;
• if you have an adrenal gland disorder called Conn's syndrome (or primary hyperaldosteronism);
• if you have ever had 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;
• inform your doctor if you suspect (or are planning) pregnancy. Use of Karbicombi is not recommended during early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child (see section "Pregnancy and breastfeeding");
• if you have previously had skin cancer or if you develop any unexpected skin changes during treatment. Treatment with hydrochlorothiazide, especially at high doses over a long period, may increase the risk of certain types of skin and lip cancers (non-melanoma skin cancer). While taking Karbicombi, protect your skin from sunlight and UV radiation;
• if you have previously experienced breathing or lung problems (including pneumonia or fluid accumulation in the lungs) after taking hydrochlorothiazide. If you develop severe shortness of breath or difficulty breathing after taking Karbicombi, seek immediate medical help;
• if you experience blurred vision or eye pain. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive accumulation of fluid between choroid and sclera) or increased intraocular pressure – these may occur from a few hours to weeks after taking Karbicombi. If left untreated, they may lead to permanent vision loss. If you have previously had an allergic reaction to penicillin or sulfonamides, you may be at higher risk of developing this condition.
• if you are taking any of the following medicines for high blood pressure:
• ACE inhibitors (e.g. enalapril, lisinopril, ramipril, etc.), especially if you have kidney problems related to diabetes,
• aliskiren.

Your doctor may monitor your kidney function, blood pressure and blood electrolyte levels (e.g. potassium) at regular intervals.
See also information under the heading "When not to take Karbicombi".
If you have any of the conditions listed above, your doctor may recommend more frequent check-ups and diagnostic tests.
If you are scheduled for surgery, inform your doctor or dentist that you are taking Karbicombi. Karbicombi may cause excessive lowering of blood pressure when used together with certain anesthetics.
Karbicombi may cause skin photosensitivity.
Children and adolescents
There is no experience with the use of Karbicombi in children (under 18 years of age), therefore it should not be used in this patient group.
Karbicombi with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, 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 some cases, your doctor may recommend periodic blood tests.
In particular, inform your doctor if you are taking any of the following medicines, as your doctor may need to adjust the dose and/or take other precautions:

• other blood pressure-lowering medicines, including beta-blockers, medicines containing aliskiren, diazoxide, and angiotensin-converting enzyme inhibitors (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);
• acetylsalicylic acid (at doses above 3 g per day) (a pain-relieving and anti-inflammatory medicine);
• potassium supplements or potassium-containing salt substitutes (medicines that increase blood potassium levels);
• calcium supplements or vitamin D;
• cholesterol-lowering medicines such as colestipol or cholestyramine;
• antidiabetic medicines (tablets or insulin);
• medicines controlling heart rhythm (antiarrhythmics), such as digoxin and beta-blockers;
• medicines whose effects may be influenced by blood potassium levels, such as certain antipsychotics;
• heparin (a blood-thinning medicine);
• diuretics (water pills);
• laxatives;
• penicillin or cotrimoxazole also known as trimethoprim/sulfamethoxazole (antibiotics);
• amphotericin (a medicine used to treat fungal infections);
• lithium (a medicine used to treat psychiatric disorders);
• steroids, such as prednisolone;
• pituitary hormone (ACTH);
• anticancer medicines;
• amantadine (a medicine used to treat Parkinson's disease or severe viral infections);
• barbiturates (a type of sedative used also in epilepsy treatment);
• carbenoxolone (a medicine used to treat esophageal disease or oral ulcers);
• anticholinergic medicines, such as atropine and biperiden;
• cyclosporine, a medicine used to prevent rejection of transplanted organs;
• other medicines that may enhance the antihypertensive effect, such as baclofen (a muscle relaxant), amifostine (an anticancer medicine), and certain antipsychotics.
• if you are taking an ACE inhibitor or aliskiren (see also information under the headings "When not to take Karbicombi" and "Warnings and precautions").

Karbicombi with food, drink and alcohol

• Karbicombi can be taken with or without food.
• Discuss with your doctor the possibility of drinking alcohol before taking Karbicombi, as alcohol may cause fainting or dizziness.

Pregnancy and breastfeeding
Pregnancy
Inform your doctor if you suspect (or are planning) pregnancy. Your doctor will usually recommend discontinuing Karbicombi before a planned pregnancy or immediately after confirming pregnancy and will recommend another medicine instead of Karbicombi. Use of Karbicombi is not recommended during early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child.
Breastfeeding
Inform your doctor if you are breastfeeding or intend to breastfeed. Use of Karbicombi is not recommended during breastfeeding. Your doctor may recommend another medicine during breastfeeding.
Driving and using machines
Some patients may experience fatigue or dizziness while taking Karbicombi. If this occurs, do not drive, use tools or operate machinery.
Karbicombi contains monohydrate lactose
If you have been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to use Karbicombi

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Karbicombi is available in the following doses: 8 mg + 12.5 mg, 16 mg + 12.5 mg, 32 mg + 12.5 mg, 32 mg + 25 mg.
It is important to take Karbicombi every day.
The usual recommended dose of Karbicombi is one tablet once daily.
The tablet should be swallowed with water.
Try to take the tablet at the same time each day, which will help you remember to take the medicine.
Taking more Karbicombi than recommended
If you take more Karbicombi than prescribed, contact your doctor or pharmacist immediately.
Missing a dose of Karbicombi
Do not take a double dose to make up for a missed dose.
Take the next dose at the usual time.
Stopping Karbicombi treatment
Stopping treatment with Karbicombi may cause blood pressure to rise again. Therefore, do not discontinue treatment with Karbicombi without consulting your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everybody will experience them.
It is important for the patient to be aware of the possible adverse reactions. Some adverse reactions
of Karbicombi are caused by candesartan cilexetil, and some by hydrochlorothiazide.
You should stop taking Karbicombi and seek immediate medical help if any of the following
allergic reactions occur:

• 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 reduction in the number of white blood cells, which may be associated
with reduced resistance to infections and the occurrence of fatigue, infection or fever. If such
symptoms occur, inform your doctor. Your doctor may recommend periodic blood tests to check
whether Karbicombi affects blood composition (agranulocytosis).
Other possible adverse reactions include:
Common (may occur in up to 1 in 10 patients):

• Changes in blood test results:
• Decreased sodium levels in the blood. If significantly reduced, 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. If levels change significantly, fatigue, weakness, heart rhythm disturbances or tingling sensations may occur.
• Increased levels of cholesterol, glucose or uric acid in the blood.
• Presence of glucose 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.
• Loss of appetite, diarrhoea, constipation, stomach irritation.
• Skin rash, urticaria, photosensitivity rash.

Rare (may occur in up to 1 in 1000 patients):

• Jaundice (yellowing of the skin or eyes). If such symptoms occur, contact your doctor immediately.
• Effects on kidney function, especially in patients with existing kidney disease or heart failure.
• Sleep disturbances, depression, anxiety.
• Tingling or prickling sensations in the upper or lower limbs.
• Transient blurred vision.
• Heart rhythm disturbances.
• Breathing difficulties (including pneumonia and fluid in the lungs).
• High temperature (fever).
• Pancreatitis, causing moderate or severe pain in the upper abdomen.
• Muscle cramps.
• Damage to blood vessels causing red or purple spots on the skin.
• Decreased number of red blood cells, white blood cells or platelets. This may result in

fatigue, infection, fever or easy bruising.

• Severe rash developing rapidly, with blistering or peeling of the skin, possibly accompanied by blisters 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 and muscle pain.
• Changes in liver function, including hepatitis. Symptoms may include 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 available data):

• Skin and lip malignancies (non-melanoma skin cancers).
• Diarrhoea.
• Sudden onset of myopia.
• Visual impairment 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 and cutaneous lupus erythematosus (allergic reaction with accompanying fever, joint pain, skin rashes including darkening, blisters, skin peeling and nodules).

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform
your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Karbicombi

Keep this medicine 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 stated month.
Do not store above 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Karbicombi contains

• The active substances are candesartan cilexetil and hydrochlorothiazide. Each tablet contains 32 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide.
• Other components are: monohydrate lactose, corn starch, macrogol 8000, hydroxypropylcellulose, calcium carmellose, magnesium stearate, yellow iron oxide (E 172).

What Karbicombi looks like and contents of the pack
Karbicombi 32 mg + 12.5 mg, tablets: yellowish-white, biconvex, oval tablets with a division line on one side.
The division line on the tablet is intended only to facilitate breaking for easier swallowing and does not ensure equal dose division.
Packaging: 28 or 56 tablets in PVC/PVDC-Al blisters packed in a cardboard box.
For more detailed information, please contact the Marketing Authorisation Holder or the Parallel Importer.
Marketing Authorisation Holder in Italy, country of export:
HCS BV, H Kennisstraat 53, B 2650 Edegem, Belgium
Manufacturer:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
Parallel Importer:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland
Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland
Marketing Authorisation number in Italy, country of export: 041126398
Parallel Import Licence Number: 323/21
This medicinal product is authorised for marketing 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
Hungary, Slovenia Candecombi
Lithuania Canocombi