Cazacombi

Package Leaflet: Information for the Patient

Cazacombi, 5 mg + 12.5 mg, Film-Coated Tablets

cilazapril + hydrochlorothiazide

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is Cazacombi and what is it used for
• 2. Important information before taking Cazacombi
• 3. How to take Cazacombi
• 4. Possible side effects
• 5. How to store Cazacombi
• 6. Contents of the pack and other information

1. What is Cazacombi and what is it used for

Cazacombi is a combination of two active substances called cilazapril and hydrochlorothiazide.
Cazacombi is used to treat high blood pressure. The two active substances work together to lower blood pressure. They are used together when treatment with one of these substances is not sufficient.
Cilazapril belongs to a group of medicines called ACE inhibitors (angiotensin-converting enzyme inhibitors). Its action is to relax and widen the blood vessels. This helps to lower blood pressure and makes it easier for the heart to pump blood to all parts of the body.
Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics or diuretics. Its action is to increase the amount of urine produced. This helps to lower blood pressure.

2. Important information before taking Cazacombi

When not to take Cazacombi:

• if you are allergic to cilazapril or hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to medicines similar to Cazacombi, such as other ACE inhibitors, thiazide diuretics, or sulfonamides;
• if you have had a severe allergic reaction called angioedema after taking other ACE inhibitors, or if you have hereditary angioedema or angioedema of unknown cause. Symptoms include swelling of the face, lips, mouth, or tongue.
• if you have severe kidney disease (creatinine clearance less than 30 ml/min) or anuria (lack of urine production);
• after the third month of pregnancy (you should also avoid taking Cazacombi during early pregnancy - see sections "Pregnancy and breast-feeding");
• if you have diabetes or kidney problems and are taking a blood pressure-lowering medicine containing aliskiren;
• if you are taking sacubitril/valsartan, a medicine used to treat a certain type of long-term (chronic) heart failure in adults, as the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) increases.

If any of the above applies to you, do not take Cazacombi. If you are in doubt, consult your doctor or pharmacist before taking Cazacombi.

Warnings and precautions

Before taking Cazacombi, discuss with your doctor or pharmacist if:

• you have heart disease - Cazacombi should not be taken by patients with certain heart diseases;
• you have had a stroke or cerebral blood flow disorders;
• you have severe liver disease or jaundice;
• you have kidney disease or renal artery stenosis;
• you are undergoing dialysis;
• you have recently had vomiting or diarrhea;
• you are on a low-sodium diet;
• you are scheduled to undergo desensitization to bee or wasp venom;
• you are scheduled to undergo surgery (including dental surgery) - some anesthetics may lower blood pressure, which may become too low;
• you have fluid in the abdominal cavity (ascites);
• you have diabetes;
• you have collagen disease;
• you are undergoing LDL apheresis using dextran sulfate;
• you have gout;
• you have porphyria;
• you have had skin cancer or if an unexpected skin change occurs during treatment. Hydrochlorothiazide treatment, especially with high doses and long-term use, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). When taking Cazacombi, protect your skin from sunlight and UV radiation;
• 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 Cazacombi, seek medical attention immediately;
• you have vision loss or eye pain. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive accumulation of fluid between the choroid and sclera) or increased pressure inside the eye - these can occur within a few hours to weeks after taking Cazacombi. If left untreated, they can lead to permanent vision loss. If you have previously been allergic to penicillin or sulfonamides, you may be more likely to develop this condition.
• you are taking any of the following medicines, as the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) increases:
• racecadotril, a medicine used to treat diarrhea;
• temsirolimus, sirolimus, everolimus, and other medicines belonging to the class of mTOR inhibitors (used to prevent rejection of transplanted organs and to treat cancer);
• wildagliptin, a medicine used to treat diabetes.
• you are taking any of the following medicines used to treat high blood pressure:
• angiotensin receptor antagonist (ARB) (also known as sartans - e.g., valsartan, telmisartan, irbesartan), especially if you have diabetic kidney disease;
• aliskiren.

Your doctor may monitor your kidney function, blood pressure, and electrolyte levels (e.g., potassium) in your blood at regular intervals.
See also the information under the heading "When not to take Cazacombi".
You must inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. Cazacombi should not be taken during early pregnancy and must not be taken after the third month of pregnancy, as it may seriously harm the baby (see section "Pregnancy and breast-feeding").

Children and adolescents

Cazacombi should not be used in children and adolescents under 18 years of age.

Cazacombi and other medicines

Tell your doctor or pharmacist about all the medicines you are taking, have recently taken, or might take, including those obtained without a prescription and herbal medicines. This is because Cazacombi may affect the action of other medicines, and some medicines may affect the action of Cazacombi.
In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• all medicines used to treat high blood pressure;
• non-steroidal anti-inflammatory medicines (NSAIDs) - these include acetylsalicylic acid, indomethacin, and ibuprofen;
• insulin or other diabetes medicines;
• lithium (used to treat depression);
• corticosteroids (such as hydrocortisone, prednisolone, and dexamethasone) or other medicines that suppress the immune system;
• potassium supplements or salt substitutes containing potassium, diuretics (water tablets, especially those that spare potassium), or other medicines that may increase potassium levels in the body (such as trimethoprim and cotrimoxazole, also known as trimethoprim/sulfamethoxazole, used to treat bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent rejection of transplanted organs and to treat cancer, and heparin, a medicine used to thin the blood to prevent blood clots);
• diuretics;
• sympathomimetics;
• anesthetics, opioids;
• tricyclic antidepressants, antipsychotics;
• gold compounds (used to treat rheumatoid arthritis);
• medicines used to treat heart failure or irregular heartbeat;
• calcium supplements and vitamin D;
• cholestyramine/colestipol (used to lower blood fat levels);
• anticholinergic medicines;
• cytotoxic medicines (e.g., methotrexate, cyclophosphamide);
• iodine-containing contrast agents (given to patients before certain radiological examinations);
• certain muscle relaxants;
• amantadine;
• medicines often used to prevent rejection of transplanted organs (sirolimus, everolimus, and other medicines belonging to the class of mTOR inhibitors. See section "Warnings and precautions").

Your doctor may need to change the dose and/or take other precautions:

• if you are taking an angiotensin receptor antagonist (ARB) or aliskiren (see also the information under the heading "When not to take Cazacombi" and "Warnings and precautions").

Cazacombi with food and drink

Cazacombi can be taken with or without food.
Tell your doctor or pharmacist if you are taking potassium supplements.

Pregnancy and breast-feeding

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

Pregnancy

Tell your doctor if you are pregnant, think you may be pregnant, or are planning to become pregnant. Your doctor will usually advise you to stop taking Cazacombi before planned pregnancy and will advise you to take a different medicine instead of Cazacombi. Cazacombi should not be taken during early pregnancy and must not be taken after the third month of pregnancy, as it may seriously harm the baby (see section "Pregnancy and breast-feeding").

Breast-feeding

Tell your doctor if you are breast-feeding or plan to breast-feed. Cazacombi should not be taken during breast-feeding, especially if you are breast-feeding a newborn or premature baby. Your doctor may advise you to take a different medicine.

Driving and using machines

While taking Cazacombi, dizziness may occur. This is more likely to happen at the start of treatment. If you feel dizzy, do not drive, use tools, or operate machinery.

Cazacombi contains lactose and sodium

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, which is essentially "sodium-free".

3. How to take Cazacombi

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.
The recommended dose is one tablet per day, taken every day.

How to take the medicine

Swallow the tablet with water.
The time of taking Cazacombi does not matter. However, you should take it at the same time every day.
Cazacombi can be taken before or after food.
Do not crush or chew the tablets.

Taking more than the recommended dose of Cazacombi

If you take more than the recommended dose of Cazacombi or if someone else takes your medicine, contact your doctor or go to the nearest hospital immediately.
Take the medicine pack with you. The following symptoms may occur: dizziness, feeling of "emptiness" in the head, shallow breathing, cold and moist skin, inability to move or speak, and slow or irregular heartbeat.

Missing a dose of Cazacombi

• If you miss a dose, skip the missed dose. Then take the next dose at the usual time.
• Do not take a double dose to make up for a missed dose.

If you have any further questions about taking this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Cazacombi can cause side effects, although not everybody gets them.

Severe side effects:

If you experience a severe allergic reaction called angioedema, stop taking Cazacombi and go to your doctor immediately. Symptoms include:

• sudden swelling of the face, throat, lips, or mouth, which may cause difficulty breathing or swallowing.

Blood disorders reported with ACE inhibitors and thiazide diuretics include:

• low red blood cell count (anemia). Symptoms include feeling tired, pale skin, fast or irregular heartbeat (palpitations), and shortness of breath.
• low white blood cell count. Symptoms include increased number of infections, such as mouth, gum, throat, and lung infections.
• low platelet count. Symptoms include easy bruising and bleeding from the nose.

Other possible side effects:

Common (may affect up to 1 in 10 people):

• dizziness
• cough
• nausea
• fatigue
• headache

Uncommon (may affect up to 1 in 100 people):

• low blood pressure. This may cause weakness, dizziness, or feeling of "emptiness" in the head, blurred vision, and fainting. Excessive lowering of blood pressure in some patients may increase the risk of heart attack or stroke.
• rapid heartbeat, palpitations
• weakness
• chest pain
• breathing difficulties, including shortness of breath and tightness in the chest
• runny or blocked nose and sneezing (rhinitis)
• dryness or swelling of the mouth, mouth pain
• loss of appetite
• change in taste
• diarrhea and vomiting
• rash (which may be severe)
• muscle cramps or muscle pain, or joint pain
• impotence
• increased sweating
• sudden flushing (especially of the face)
• sleep disturbances
• decreased red blood cell count, white blood cell count, or platelet count, found in blood tests (anemia, neutropenia, agranulocytosis, and thrombocytopenia)
• abnormal levels of electrolytes (sodium, potassium, chloride, magnesium, calcium, bicarbonate) or increased levels of glucose, uric acid, cholesterol, and triglycerides, found in blood tests
• a type of severe allergic reaction (anaphylaxis)
• cerebral hypoperfusion, transient ischemic attack, ischemic stroke (may occur if blood pressure is too low)
• myocardial infarction (may occur if blood pressure is too low)
• arrhythmias
• interstitial lung disease
• pulmonary edema
• a condition similar to systemic lupus erythematosus
• tingling or numbness of the hands or feet
• wheezing
• bronchitis
• sinusitis
• irritation of the tongue
• pancreatitis - symptoms include severe abdominal pain radiating to the back
• liver or kidney function disorders (found in blood and urine tests)
• kidney disorders
• liver disorders, such as hepatitis or liver damage
• severe skin reactions, including blisters or peeling of the skin
• increased sensitivity to light
• hair loss (which may be temporary)
• loosening or separation of the nail from the nail bed
• breast enlargement in men
• depression
• confusion
• dry eyes
• yellow vision

Rare (may affect up to 1 in 10,000 people)

• acute respiratory failure (symptoms include severe shortness of breath, fever, weakness, and confusion).

Frequency not known (cannot be estimated from the available data)

• skin cancer and lip cancer (non-melanoma skin cancer)
• vision loss or eye pain due to increased pressure (possible symptoms of fluid accumulation in the vascular layer surrounding the eye - excessive accumulation of fluid between the choroid and sclera - or acute angle-closure glaucoma)

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, 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 Cazacombi

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 packaging (after "EXP"). The expiry date refers to the last day of that month.
Store in the original package to protect from moisture.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Cazacombi contains

• The active substances are cilazapril and hydrochlorothiazide. Each film-coated tablet contains 5 mg cilazapril (as cilazapril monohydrate) and 12.5 mg hydrochlorothiazide.
• The other ingredients are sodium stearylfumarate, talc, lactose monohydrate, hypromellose, corn starch; and hypromellose, talc, titanium dioxide (E 171), iron oxide red (E 172) in the tablet coating. See section 2 "Cazacombi contains lactose and sodium".

What Cazacombi looks like and contents of the pack

Pink, oval, biconvex film-coated tablets, 10.5 mm x 5.5 mm in size.
Packaging: 28 or 30 film-coated tablets in blisters, in a cardboard box.

Marketing authorization holder and manufacturer

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
Date of last revision of the leaflet:06.02.2022