Package Insert: Information for the Patient

Karbicombi 32 mg/12.5 mg Tablets EFG

candesartán cilexetilo/hidroclorotiazida

Read this package insert carefully before starting to take this medication, because

it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. What is Karbicombi and how is it used

2.What you need to knowbefore starting to take Karbicombi

3. How to take Karbicombi

4. Possible adverse effects

5. Storage of Karbicombi

6.Contents of the package and additional information

Your medication is called Karbicombi. It is used for the treatment of high blood pressure (hypertension). It contains two active ingredients: candesartan cilexetilo and hydrochlorothiazide.

Both work together to lower your blood pressure.

Candesartan cilexetilo belongs to a group of medications called angiotensin II receptor antagonists. It makes your blood vessels relax and dilate. This facilitates a decrease in your blood pressure.

Hydrochlorothiazide belongs to a group of medications called diuretics. It promotes your body to eliminate water and salt, such as sodium, in your urine. This facilitates a decrease in your blood pressure.

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

Do not takeKarbicombi

• if you are allergic to candesartan cilexetilo or hydrochlorothiazide or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to sulfonamides. If you are unsure whether you are in this situation, consult your doctor.
• if you are more than 3 months pregnant (it is also best not to take Karbicombi in the first months of pregnancy – see Pregnancy section).
• if you have severe kidney disease.
• if you have severe liver disease or bile duct obstruction (problem with the bile flowing out of the gallbladder).
• if you have persistent low levels of potassium in the blood.
• if you have persistent high levels of calcium in the blood.
• if you have ever had gout.
• if you have diabetes or kidney insufficiency and are being treated with a blood pressure-lowering medicine containing aliskiren.

If you are unsure whether 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 have diabetes.
• if you have heart, liver or kidney problems.
• if you have recently had a kidney transplant.
• if you have frequent or severe vomiting or have diarrhea.
• if you have a condition called Conn's syndrome (also known as primary aldosteronism).
• if you have ever had a condition called systemic lupus erythematosus (SLE).
• if you have low blood pressure.
• if you have ever had a stroke.
• if you have had an allergy or asthma.
• if you are pregnant, think you may be pregnant or plan to become pregnant, inform your doctor. Candesartan/hydrochlorothiazide is not recommended during the first 3 months of pregnancy and should not be administered after the third month of pregnancy because it may cause serious harm to your baby (see Pregnancy section).
• if you have had skin cancer or if you develop an unexpected skin lesion during treatment. The treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). Protect your skin from the sun and UV rays while taking Karbicombi.
• if you have had respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience severe shortness of breath or difficulty breathing after taking Karbicombi, seek medical attention immediately.
• if you experience a decrease in vision or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye and may occur within a few hours to a week after taking this medicine. This may lead to permanent visual impairment if not treated. If you have previously had an allergy to penicillin or sulfonamide, you may be at a higher risk of developing it.
• if you are taking any of the following medicines used to treat high blood pressure (hypertension):
• a renin-angiotensin-aldosterone system (RAAS) inhibitor (e.g. enalapril, lisinopril, ramipril etc.), particularly if you have kidney problems related to diabetes,
• aliskiren.

Your doctor may monitor your renal function, blood pressure, and electrolyte levels in the blood (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 to undergo surgery, inform your doctor or dentist that you are taking Karbicombi. This is because Karbicombi, in combination with some anesthetics, may cause an excessive 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).

Therefore, Karbicombi should not be administered to children.

Other medicines and Karbicombi

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine.

Karbicombi may affect the way some medicines work and some medicines may affect the effect of Karbicombi. If you are taking certain medicines, your doctor may need to perform blood tests at regular intervals.

Especially, inform your doctor if you are taking any of the following medicines, as your doctor may need to modify your dose and/or take other precautions:

• other medicines to lower your blood pressure, including beta-blockers, medicines containing aliskiren, diazoxide, and the so-called RAAS 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).
• aspirin, if you take more than 3 g per day (medicine to relieve pain and inflammation).
• potassium supplements or salt substitutes containing potassium (medicines to increase potassium levels in the blood).
• calcium supplements or vitamin D.
• medicines to lower cholesterol, such as colestipol or colestiramine.
• medicines for diabetes (tablets or insulin).
• medicines to control heart rhythm (antiarrhythmic 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 excretion).
• 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 cancer treatment.
• 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 mouth ulcers).
• anticholinergic agents such as atropine and biperiden.
• ciclosporin, a medicine used in organ transplantation to prevent organ rejection.
• Other medicines that may enhance the antihypertensive effect, such as baclofen (a medicine for muscle spasticity), amifostin (used in cancer treatment) and some antipsychotic medicines.
• If you are taking an RAAS inhibitor or aliskiren (see also the 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 you are prescribed Karbicombi, consult your doctor before taking alcohol. Alcohol may cause dizziness or fainting.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

You should inform your doctor if you think you are pregnant (or may be). Your doctor will usually advise you to stop taking Karbicombi before becoming pregnant or as soon as you know you are pregnant and recommend that you take another medicine instead of Karbicombi.Karbicombi is not recommended during pregnancy, and it should not be taken if you are more than three months pregnant, as it may cause serious harm to your baby (see Pregnancy section).

Breastfeeding

Inform your doctor if you are breastfeeding or plan to start breastfeeding. Karbicombi is not recommended for breastfeeding mothers, and your doctor may choose another treatment for you if you want to breastfeed.

Driving and operating machines

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

Karbicombi contains lactose

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

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, ask your doctor or pharmacist.

It is essential to continue taking 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 every day. This will help you remember to take it.

If you take more Karbicombi than you should

In case of an 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 Toxicological Information Service, phone 91 562 04 20 indicating the medication and the amount ingested.

If you forgot to take Karbicombi

Do not take a double dose to compensate for the missed dose.

Simply take the next dose.

If you interrupt treatment with Karbicombi

If you stop taking Karbicombi, your blood pressure may increase again. Therefore, do not stop taking Karbicombi before consulting your doctor.

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

Like all medicines, this medicine can have side effects, although not everyone will experience them. It is important that you know which side effects could occur. Some side effects of Karbicombi are due to candesartán cilexetilo and others are due to hydrochlorothiazide.

Stop taking Karbicombi and see your doctor 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 skin itching (skin 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 fever. If this occurs, inform your doctor. It is possible that your doctor will perform blood tests from time to time to check that Karbicombi is not affecting your blood (agranulocytosis).

Other possible side effects include:

Frequent(may affect up to 1 in 10 people)

-Changes in blood test results:

-A reduction in sodium levels in the blood. If severe, you may feel weak, lack energy, or experience muscle cramps.

-An increase or decrease in potassium levels in the blood, especially if you already have kidney problems or heart failure. If this is severe, you will feel tired, weak, experience irregular heartbeats, or numbness.

-An increase in cholesterol, glucose, or uric acid levels in the blood.

-Presence of glucose in the urine.

-Dizziness or weakness.

-Headache.

-Respiratory infection.

Infrequent(may affect up to 1 in 100 people)

-Low blood pressure. This may cause dizziness or fainting.

-Loss of appetite, diarrhea, constipation, stomach irritation.

-Skin rash, hives, photosensitivity reaction.

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

-Jaundice (yellowing of the skin and white of the eyes). If this occurs, contact your doctor immediately.

-Effects on kidney function, especially if you already have kidney problems or heart failure.

-Difficulty sleeping, depression, or restlessness.

-Itching or prickling in arms and legs.

-Blurred vision for a short period of time.

-Abnormal heartbeats.

-Difficulty breathing (including pulmonary inflammation and fluid in the lungs).

-Fever.

-Pancreatitis. This causes moderate to severe stomach pain.

-Muscle cramps.

-Vascular damage that produces red or purple spots on the skin.

-Decrease in red blood cells, white blood cells, or platelets. You may feel tired, have an infection, fever, or easily bruise.

-Severe skin reaction that develops rapidly, causing blisters and skin peeling, and possibly mouth ulcers.

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 will feel tired, have a yellowish discoloration of the skin and white of the eyes, and experience flu-like symptoms.

-Cough.

-Nausea.

• Acute respiratory distress (symptoms include severe difficulty breathing, fever, weakness, and confusion).

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

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

-Sudden myopia.

-Decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) or acute angle-closure glaucoma).

-SLE and cutaneous lupus (allergic condition that causes fever, joint pain, skin eruptions that may include redness, blisters, exfoliation, and nodules).

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system: Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

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

Do not store at a temperature above 30°C.

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

This medication does not require any special storage temperature.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and the

medicines that you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and the medicines that you no longer need. By doing so, you will help protect the environment.

Composition of Karbicombi

• The active principles are candesartan cilexetilo and hydrochlorothiazide.

Each tablet contains 32 mg of candesartan cilexetilo and 12.5 mg of hydrochlorothiazide.

• The other components are lactose monohydrate, cornstarch, hydroxypropylcellulose,

magnesium stearate, calcium carmelose, macrogol 8000, and yellow iron oxide E-172.See section 2: “Karbicombi contains lactose”.

Appearance of Karbicombi and contents of the package

Karbicombi 32 mg/12.5 mg tablets are yellowish white, biconvex, oval, with a notch on one side.

The notch serves to split and facilitate swallowing but not to divide into equal doses.

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

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible manufacturer

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

You can request more information about this medication 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 medication is authorized in the member states of the European Economic Area with the following names:

Date of the last review of this prospectus:February 2022

Detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/