KARBICOMBI 16 mg/12.5 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Karbicombi 16 mg/12.5 mg tablets EFG

candesartan cilexetil/hydrochlorothiazide

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet, you may need to read it again.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

1. What is Karbicombi and what is it used for
2. What you need to know before you take Karbicombi
3. How to take Karbicombi
4. Possible side effects

5 Storage of Karbicombi

1. Contents of the pack and further information

1. What is Karbicombi and what is it used for

Your medicine is called Karbicombi. It is used to treat high blood pressure (hypertension). It contains two active substances: candesartan cilexetil and hydrochlorothiazide.

Both substances work together to lower your blood pressure.

Candesartan cilexetil belongs to a group of medicines called angiotensin II receptor antagonists. It makes your blood vessels relax and dilate. This helps to lower your blood pressure.

Hydrochlorothiazide belongs to a group of medicines called diuretics. It helps your body get rid of water and salts such as sodium in your urine. This helps to lower your blood pressure.

Your doctor may prescribe Karbicombi if your blood pressure is not adequately controlled with candesartan cilexetil or hydrochlorothiazide alone.

2. What you need to know before you take Karbicombi

Do not takeKarbicombi

• 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 sulfonamides. If you are not sure, consult your doctor.
• if you are more than 3 months pregnant (it is also better not to take Karbicombi during the first months of pregnancy - see section on Pregnancy).
• if you have severe kidney disease.
• if you have severe liver disease or biliary obstruction (problem with bile secretion from the gallbladder).
• if you have persistent low potassium levels in your blood.
• if you have persistent high calcium levels in your blood.
• if you have ever had gout.
• if you have diabetes or kidney problems and are being treated with a blood pressure medicine that contains aliskiren.

If you are not sure if you are in any of these situations, consult your doctor or pharmacist before taking Karbicombi.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Karbicombi:

• if you are diabetic.
• if you have heart, liver, or kidney problems.
• if you have recently had a kidney transplant.
• if you have had frequent or severe vomiting or have diarrhea.
• if you have a disease of the adrenal gland called Conn's syndrome (also known as primary hyperaldosteronism).
• if you have ever had a disease called systemic lupus erythematosus (SLE).
• if you have low blood pressure.
• if you have ever had a stroke.
• if you have ever had an allergy or asthma.
• if you are pregnant, think you may be pregnant, or plan to become pregnant, you must inform your doctor. Karbicombi is not recommended during pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby (see section on Pregnancy).
• if you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, especially long-term use at high doses, may increase the risk of some types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Karbicombi.
• If you have had respiratory or lung problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience shortness of breath or severe difficulty breathing after taking Karbicombi, seek medical attention immediately.
• if you experience a decrease in vision or eye pain. They could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye and can occur within hours to a week after taking this medicine. This can lead to permanent visual impairment if left untreated. If you have previously been allergic to penicillin or sulfonamide, you may be at higher risk of developing it.
• if you are taking any of the following medicines used to treat high blood pressure (hypertension):
• an ACE inhibitor (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 the information under the heading "Do not take Karbicombi".

If you are in any of these situations, your doctor may want to see you more frequently and perform more tests.

If you are going to have surgery, inform your doctor or dentist that you are taking Karbicombi. This is because Karbicombi, in combination with some anesthetics, can cause a significant drop in blood pressure.

Karbicombi may increase your skin's sensitivity to the sun.

Children and adolescents

There is no experience with the use of Karbicombi in children (under 18 years of age).

Therefore, Karbicombi should not be given to children.

Other medicines and Karbicombi

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Karbicombi may affect the way some medicines work and some medicines may affect the effect of Karbicombi. If you are using certain medicines, your doctor may need to perform blood tests from time to time.

In particular, inform your doctor if you are using any of the following medicines, as your doctor may need to change your dose and/or take other precautions:

• other medicines to lower your blood pressure, including beta-blockers, medicines that contain aliskiren, diazoxide, and the so-called ACE inhibitors such as enalapril, captopril, lisinopril, or ramipril.
• non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, or diclofenac, celecoxib, or etoricoxib (medicines to reduce pain and inflammation).
• acetylsalicylic acid, if you take more than 3 g per day (medicine to relieve pain and inflammation).
• potassium supplements or salt substitutes that contain potassium (medicines to increase potassium levels in the blood).
• calcium supplements or vitamin D.
• medicines to lower cholesterol, such as colestipol or cholestyramine.
• medicines for diabetes (tablets or insulin).
• medicines to control heart rhythm (anti-arrhythmic agents) such as digoxin and beta-blockers.
• Medicines that may be affected by potassium levels in the blood, such as some antipsychotic medicines.
• heparin (a medicine to increase blood fluidity).
• diuretics (medicines to promote urine elimination).
• laxatives.
• penicillin or co-trimoxazole, also known as trimethoprim/sulfamethoxazole (antibiotic medicines)
• amphotericin (for the treatment of fungal infections).
• lithium (a medicine for mental health problems).
• steroids such as prednisolone.
• pituitary hormone (ACTH).
• medicines for the treatment of cancer.
• amantadine (for the treatment of Parkinson's disease or severe viral infections).
• barbiturates (a type of sedative, also used to treat epilepsy).
• carbenoxolone (for the treatment of esophageal disease or oral ulcers).
• anticholinergic agents such as atropine and biperiden.
• Cyclosporin, a medicine used in organ transplantation to prevent organ rejection.
• Other medicines that may enhance the anti-hypertensive effect, such as baclofen (a medicine for the relief of spasticity), amifostine (used in cancer treatment), and some antipsychotic medicines.
• If you are taking an ACE inhibitor or aliskiren (see also information under the headings "Do not take Karbicombi" and "Warnings and precautions").

Taking Karbicombi with food, drinks, and alcohol

• You can take Karbicombi with or without food.

When Karbicombi is prescribed, consult your doctor before consuming alcohol. Alcohol may make you feel dizzy or faint

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

You should tell your doctor if you think you are pregnant (or might be). Your doctor will normally advise you to stop taking Karbicombi before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Karbicombi. Karbicombi is not recommended during pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breastfeeding

Tell your doctor if you are breastfeeding, or about to start breastfeeding. Karbicombi is not recommended for mothers who are breastfeeding, and your doctor may choose another treatment for you if you wish to breastfeed.

Driving and using machines

Some patients may feel tired or dizzy when taking Karbicombi. If this happens to you, do not drive or use tools or machines.

Karbicombi contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Karbicombi

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.

It is important that you take Karbicombi every day.

The recommended dose is one tablet once a day.

Swallow the tablet with a glass of water.

Try to take the tablet at the same time each day. This will help you remember to take it.

If you take more Karbicombi than you should

In case of overdose, contact your doctor immediately or go directly to the hospital for immediate medical attention.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Karbicombi

Do not take a double dose to make up for a forgotten dose.

Just take the next dose as normal.

If you stop taking Karbicombi

If you stop taking Karbicombi, your blood pressure may increase again. Therefore, do not stop taking Karbicombi without consulting your doctor first.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. It is important that you know what these side effects may be. Some of the side effects of Karbicombi are due to candesartan cilexetil and others are due to hydrochlorothiazide.

Stop taking Karbicombi and go to your doctor immediately if you have 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 rash).

Karbicombi may cause a decrease in white blood cells. Your resistance to infections may decrease and you may feel tired, have an infection, or have a fever. If this happens, inform your doctor. Your doctor may perform blood tests from time to time to check that Karbicombi is not affecting your blood (agranulocytosis).

Other possible side effects include:

Common(may affect up to 1 in 10 people)

• Changes in blood test results:
• A decrease in sodium levels in the blood. If severe, you may feel weak, lack energy, or have muscle cramps.
• An increase or decrease in potassium levels in the blood, especially if you already have kidney problems or heart failure. If this situation is severe, you may feel tired, weak, have irregular heartbeats, or have tingling.
• An increase in cholesterol, glucose, or uric acid levels in the blood.
• Presence of glucose in urine.
• Feeling dizzy or weak.
• Headache.
• Respiratory infection.

Uncommon(may affect up to 1 in 100 people) - Low blood pressure. This may cause you to feel dizzy or faint.

• Loss of appetite, diarrhea, constipation, stomach upset.
• Rash, hives, skin reaction caused by sensitivity to sunlight.

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

• Jaundice (yellowing of the skin and the whites of the eyes). If this happens, contact your doctor immediately.
• Effects on kidney function, especially if you already have kidney problems or heart failure.
• Difficulty sleeping, depression, or restlessness.
• Tingling or pinching in arms and legs.
• Blurred vision for a short time.
• Abnormal heartbeats.
• Breathing difficulties (including pulmonary inflammation and fluid in the lungs).
• High temperature (fever).
• Pancreatitis. This causes moderate to severe stomach pain.
• Muscle cramps.
• Damage to blood vessels that produce red or purple spots on the skin.
• A decrease in red blood cells, white blood cells, or platelets. You may feel tired, have an infection, fever, or bruise easily.
• A severe skin reaction that develops rapidly, causing blisters and peeling of the skin, and possibly ulcers 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 and muscle pain.
• Changes in liver function, including liver inflammation (hepatitis). You may feel tired, have yellowing of the skin and the whites of the eyes, and have flu-like symptoms.
• Cough.
• Nausea
• Acute breathing difficulties (signs include severe breathing difficulties, fever, weakness, and confusion).

Side effects of unknown frequency(cannot be estimated from the available data)

• Skin and lip cancer (non-melanoma skin cancer).

• Sudden onset of short-sightedness.
• Decreased vision or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma).
• Systemic lupus erythematosus and cutaneous lupus (an allergic condition that causes fever, joint pain, skin rashes that can include redness, blisters, peeling, and lumps).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system: Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Karbicombi

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

Tablets in PVC/PVDC film-coated blister packs and aluminum foil:

Do not store above 30°C.

Tablets in OPA/Al/PVC film-coated blister packs and aluminum foil:

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Return any unused medicine to your pharmacist. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Karbicombi Composition

• The active ingredients are candesartan cilexetil and hydrochlorothiazide.

Each tablet contains 16 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide.

• The other components are lactose monohydrate, corn starch, hydroxypropylcellulose, magnesium stearate, calcium carmellose, macrogol 8000, and red iron oxide E-172. See section 2: "Karbicombi contains lactose".

Appearance of Karbicombi and Container Content

Karbicombi 16 mg/12.5 mg tablets are pale pink, biconvex, oval, with a score line on one side.

The score line is used for breaking and facilitating swallowing, but not for dividing into equal doses.

Available in blisters of 14, 15, 28, 30, 56, 60, 84, 90, 98 tablets in a box.

High-density polyethylene (HDPE, white) bottle with a polypropylene (PP) tamper-evident closure: 100 film-coated tablets in a cardboard box.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

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

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

KRKA Farmacéutica, S.L., C/ Anabel Segura 10, Pta. Baja, Oficina 1, 28108 Alcobendas, Madrid, Spain

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

Date of the Last Revision of this Leaflet:February 2022

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

/