Perindopril and indapamide Zentiva

Patient Information Leaflet: Information for the User

Perindopril and Indapamide Zentiva 4 mg+1.25 mg tablets

Generic medicine
Please read all of this leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Never give it to other people, even if their symptoms seem identical to yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Perindopril and Indapamide Zentiva 4 mg+1.25 mg is and what it is used for
2. What you need to know before taking Perindopril and Indapamide Zentiva 4 mg+1.25 mg
3. How to take Perindopril and Indapamide Zentiva 4 mg+1.25 mg
4. Possible side effects
5. How to store Perindopril and Indapamide Zentiva 4 mg+1.25 mg
6. Contents of the pack and other information

1. What Perindopril and Indapamide Zentiva 4 mg+1.25 mg is and what it is used for

Perindopril and Indapamide Zentiva 4 mg+1.25 mg is a combination of two active substances, perindopril and indapamide.
It is an antihypertensive medicine used in the treatment of high blood pressure (hypertension).
Perindopril belongs to a class of medicines called ACE inhibitors. These medicines work by dilating blood vessels, making it easier for the heart to pump blood through them.
Indapamide is a diuretic. Diuretics increase the amount of urine produced by the kidneys. However, indapamide differs from other diuretics in that it causes only a slight increase in the amount of urine produced.
Each active substance reduces blood pressure, and together they act to control blood pressure.

2. What you need to know before taking Perindopril and Indapamide Zentiva 4 mg+1.25 mg

Do not take Perindopril and Indapamide Zentiva 4 mg+1.25 mg

• if you are allergic to perindopril or to any other ACE inhibitor;
• if you are allergic to indapamide or to any other sulfonamide;
• if you are allergic to any of the other ingredients of this medicine (listed in section 6);
• if you have previously experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin rashes related to prior treatment with ACE inhibitors, or if you or a family member has ever had such symptoms under any circumstances (a condition called angioedema);
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren;
• if you have severe liver disease or suffer from a condition called hepatic encephalopathy (a degenerative brain disorder);
• if you have severe kidney disease, particularly with reduced blood flow to the kidneys (renal artery stenosis);
• if you are undergoing dialysis or any form of blood filtration. Depending on the equipment used,
  treatment with Perindopril and Indapamide Zentiva may not be suitable for you,
• if you have low plasma potassium levels,
• if you suspect you have untreated decompensated heart failure (severe fluid retention, breathing difficulties),
• if you are more than 3 months pregnant. (It is advisable to avoid Perindopril and Indapamide Zentiva 4 mg+1.25 mg even in early pregnancy – see section “Pregnancy and Breast-feeding”),
• if you are breast-feeding,
• if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as the risk of angioedema (rapid subcutaneous swelling, e.g., in the throat) may increase.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Perindopril and Indapamide Zentiva 4 mg+1.25 mg:

• if you have aortic stenosis (narrowing of the main artery leaving the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the artery supplying blood to the kidneys);
• if you suffer from heart failure or other heart problems;
• if you have kidney problems or are on dialysis;
• if you have abnormally high levels of a hormone called aldosterone in the blood (primary aldosteronism);
• if you have liver problems;
• if you have a connective tissue disease (skin disease) such as systemic lupus erythematosus (a specific chronic inflammation) or scleroderma;
• if you suffer from atherosclerosis (hardening of the arteries);
• if you have hyperparathyroidism (overactivity of the parathyroid glands);
• if you suffer from gout;
• if you have diabetes;
• if you are on a salt-restricted diet or use potassium-containing salt substitutes;
• if you are taking lithium or potassium-sparing medicines (spironolactone, triamterene) or potassium supplements, as their use with Perindopril and Indapamide Zentiva 4 mg+1.25 mg should be avoided (see “Taking Perindopril and Indapamide Zentiva 4 mg+1.25 mg with other medicines”);
• if you are elderly;
• if you have experienced photosensitivity reactions;
• if you develop vision disturbances or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased intraocular pressure, which may occur within hours or weeks of taking Perindopril and Indapamide Zentiva. This may lead to permanent vision loss if not treated. If you previously had an allergy to penicillin or sulfonamides, you may be at higher risk of developing such reactions.
• if you are taking any of the following medicines for high blood pressure:
• an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans – e.g., valsartan, telmisartan, irbesartan), particularly if you have diabetes-related kidney problems;
• aliskiren.
  Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g., potassium) at regular intervals. See also the section "Do not take Perindopril and Indapamide Zentiva".
• if you are of African descent, as you may have a higher risk of angioedema and this medicine may be less effective in lowering your blood pressure compared to non-black patients;
• if you are a patient undergoing haemodialysis with high-flux membranes;
• if you are taking any of the following medicines, which increase the risk of angioedema:
• racecadotril (used to treat diarrhoea),
• sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of so-called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment),
• vildagliptin, a medicine used to treat diabetes.

Angioedema
Angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat, causing difficulty in swallowing or breathing) has been reported in patients treated with ACE inhibitors, including perindopril + indapamide. This may occur at any time during treatment. If you develop such symptoms, stop treatment with Perindopril and Indapamide Zentiva and contact a doctor immediately. See also section 4.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Perindopril and Indapamide Zentiva 4 mg+1.25 mg is not recommended during early pregnancy and must not be taken after the first 3 months of pregnancy, as it may cause serious harm to the unborn child (see “Pregnancy and breast-feeding”).
If you are taking Perindopril and Indapamide Zentiva 4 mg+1.25 mg, inform your general practitioner or medical staff:

• if you are scheduled for anaesthesia and/or surgery,
• if you have recently had diarrhoea or vomiting, or if you are dehydrated,
• if you are scheduled for dialysis or LDL apheresis (blood purification to remove cholesterol using a machine),
• if you are undergoing desensitisation treatment to reduce the effects of an allergy to bee or wasp stings,
• if you are scheduled for a medical examination requiring injection of an iodinated contrast medium (a substance used to make organs such as kidneys or stomach visible on X-rays),
• if you experience vision changes or pain in one or both eyes while taking Perindopril and Indapamide Zentiva. This could indicate the development of glaucoma, increased pressure in one or both eyes. Stop treatment with Perindopril and Indapamide Zentiva and consult a doctor.

Athletes should be aware that Perindopril and Indapamide Zentiva 4 mg+1.25 mg contains an active substance (indapamide) that may lead to a positive result in anti-doping tests.

Children and adolescents
Perindopril and Indapamide Zentiva 4 mg+1.25 mg must not be administered to children or adolescents.

Other medicines and Perindopril and Indapamide Zentiva 4 mg+1.25 mg
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Do not take Perindopril and Indapamide Zentiva 4 mg+1.25 mg with:

• lithium (used to treat manic disorder and depression);
• aliskiren (a medicine used to treat hypertension) if you do not have diabetes or kidney problems;
• potassium-sparing diuretics (such as triamterene, amiloride), potassium salts (including salt substitutes), and other medicines that may increase blood potassium levels (such as heparin, a medicine used to thin the blood to prevent clotting; trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole for bacterial infections);
• estramustine (used in cancer therapy);
• other medicines used to treat high blood pressure: angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers.

Treatment with Perindopril and Indapamide Zentiva 4 mg+1.25 mg may be affected by other medicines.
Your doctor may need to adjust the dose and/or take other precautions. Make sure to inform your doctor if you are taking any of the following medicines, as special attention may be required:

• other medicines for high blood pressure, including an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also “Do not take Perindopril and Indapamide Zentiva 4 mg+1.25 mg” and “Warnings and precautions”) or diuretics (medicines that increase urine production by the kidneys);
• potassium-sparing diuretics used in heart failure treatment: eplerenone and spironolactone at doses between 12.5 mg and 50 mg daily;
• medicines mainly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus and other so-called mTOR inhibitors). See section “Warnings and precautions”;
• sacubitril/valsartan (used for long-term treatment of heart failure). See sections “Do not take Perindopril and Indapamide Zentiva 4 mg+1.25 mg” and “Warnings and precautions”;
• anaesthetics;
• iodinated contrast agents;
• moxifloxacin, sparfloxacin (antibiotics used to treat infections);
• methadone (used for addiction treatment);
• procainamide (for irregular heartbeat);
• allopurinol (for gout treatment);
• mizolastine, terfenadine or astemizole (antihistamines for hay fever or allergies);
• corticosteroids used to treat various conditions including severe asthma and rheumatoid arthritis;
• immunosuppressants used to treat autoimmune diseases or to prevent transplant rejection (e.g., cyclosporine, tacrolimus);
• injectable erythromycin (an antibiotic);
• halofantrine (used to treat certain types of malaria);
• pentamidine (used to treat pneumonia);
• injectable gold (used to treat rheumatoid polyarthritis);
• vincamine (used to treat symptomatic cognitive disorders in the elderly, including memory loss);
• bepridil (used to treat angina pectoris);
• sultopride (for psychosis treatment);
• medicines used to treat heart rhythm disorders (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol);
• cisapride, difemanil (used to treat gastrointestinal and digestive problems);
• digoxin or other cardiac glycosides (for heart problems);
• baclofen (to treat muscle stiffness in conditions such as multiple sclerosis);
• medicines for diabetes such as insulin, metformin or gliptins;
• calcium, including calcium supplements;
• stimulant laxatives (e.g., senna);
• Non-Steroidal Anti-Inflammatory Drugs (e.g., ibuprofen) or high-dose salicylates (e.g., aspirin);
• injectable amphotericin B (for severe fungal infections);
• medicines for mental disorders such as depression, anxiety, schizophrenia (e.g., tricyclic antidepressants, neuroleptics);
• tetracosactide (for Crohn’s disease);
• trimethoprim (for infection treatment);
• vasodilators, including nitrates (substances that widen blood vessels);
• medicines used to treat low blood pressure, shock, or asthma (e.g., ephedrine, noradrenaline or adrenaline).

Perindopril and Indapamide Zentiva 4 mg+1.25 mg with food and drink
It is preferable to take Perindopril and Indapamide Zentiva 4 mg+1.25 mg before a meal.

Pregnancy and breast-feeding
If you are pregnant, think you may be pregnant, planning a pregnancy, or are breast-feeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
Inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Perindopril and Indapamide Zentiva 4 mg+1.25 mg before starting a pregnancy or as soon as you know you are pregnant, and will recommend an alternative medicine. Perindopril and Indapamide Zentiva 4 mg+1.25 mg is not recommended during early pregnancy and must not be taken after the first 3 months of pregnancy, as it may cause serious harm to the unborn child if taken beyond the third month of pregnancy.

Breast-feeding
Inform your doctor immediately if you are breast-feeding or planning to start. You must not take Perindopril and Indapamide Zentiva 4 mg+1.25 mg while breast-feeding. Your doctor may choose an alternative treatment if you wish to breast-feed, especially if your baby is a newborn or was born prematurely.
Inform your doctor immediately.

Driving and using machines
Perindopril and Indapamide Zentiva 4 mg+1.25 mg normally does not affect alertness, but in some patients, side effects such as dizziness or fatigue related to blood pressure reduction may occur. If you experience such symptoms, your ability to drive or operate machinery may be impaired.

Perindopril and Indapamide Zentiva 4 mg+1.25 mg contains lactose monohydrate
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Perindopril and Indapamide Zentiva 4 mg+1.25 mg

Take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, consult your doctor or pharmacist.
The recommended dose is one tablet daily.
Your doctor may decide to adjust the dose if you have renal impairment. Take the tablet preferably in the morning and before a meal.
Swallow the tablet with a glass of water.
The tablet can be divided into equal doses.

If you take more Perindopril and Indapamide Zentiva 4 mg+1.25 mg than you should
If you have taken an excessive amount of tablets, contact your doctor immediately or go immediately to the nearest emergency department. The most likely effect in case of overdose is a drop in blood pressure. If a marked drop in blood pressure occurs (associated with nausea, vomiting, cramps, dizziness, drowsiness, mental confusion, changes in the amount of urine produced by the kidneys), it may help to lie down with your legs raised.

If you forget to take Perindopril and Indapamide Zentiva 4 mg+1.25 mg
It is important to take the medicine every day, as regular treatment is more effective. However, if you forget to take a dose of Perindopril and Indapamide Zentiva 4 mg+1.25 mg, take the next dose at your usual time.
Do not take a double dose to make up for the forgotten dose.

If you stop taking Perindopril and Indapamide Zentiva 4 mg+1.25 mg
Since treatment for high blood pressure is usually lifelong, you must speak with your doctor before stopping this medicine.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking the medicine immediately and contact your doctor straight away if you experience any of the
following:

• Severe dizziness or fainting due to low blood pressure (common – may affect up to 1 in 10 people),
• Bronchospasm (tightness in the chest, wheezing and breathlessness) (uncommon – may affect up to 1 in 100 people),
• Swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (see section 2 “Warnings and precautions”) (uncommon – may affect up to 1 in 100 people),
• Severe skin reactions, including erythema multiforme (a rash that often starts with itchy red patches on the face, arms or legs) or severe rash, hives, widespread skin redness, severe itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome) or other allergic reactions (very rare – may affect up to 1 in 10,000 people),
• Cardiovascular disorders [irregular heartbeat, angina pectoris (chest, jaw and back pain caused by physical exertion), heart attack] (very rare – may affect up to 1 in 10,000 people),
• Weakness in arms or legs, or speech problems which could be signs of a possible stroke (very rare – may affect up to 1 in 10,000 people),
• Inflammation of the pancreas which may cause severe abdominal pain and backache accompanied by feeling unwell (very rare – may affect up to 1 in 10,000 people),
• Yellowing of the skin or eyes (jaundice), which could be a sign of hepatitis (very rare – may affect up to 1 in 10,000 people),
• Life-threatening irregular heartbeat (frequency not known – frequency cannot be estimated from available data),
• Brain disorder caused by liver disease (hepatic encephalopathy) (frequency not known – frequency cannot be estimated from available data).

In decreasing order of frequency, possible side effects include:
Common (may affect up to 1 in 10 people):

• Skin reactions in people predisposed to allergies and asthmatic reactions,
• Headache,
• Dizziness,
• Vertigo,
• Tingling sensation (paraesthesia),
• Visual disturbances,
• Tinnitus (ringing or noise in the ears),
• Cough,
• Shortness of breath (dyspnoea),
• Gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, indigestion or difficulty digesting, diarrhoea, constipation),
• Allergic reactions (such as skin rashes, itching),
• Muscle cramps,
• Feeling of tiredness.

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

• Mood changes,
• Sleep disorders,
• Hives (urticaria),
• Purpura (small red spots on the skin),
• Clustered blisters,
• Kidney problems,
• Impotence,
• Sweating, increased eosinophils (a type of white blood cells),
• Changes in laboratory parameters: high blood potassium levels (reversible upon discontinuation), low blood sodium levels,
• Drowsiness,
• Fainting,
• Palpitations (awareness of heartbeat),
• Tachycardia (fast heartbeat),
• Hypoglycaemia (low blood sugar levels) in diabetic patients,
• Vasculitis (inflammation of blood vessels),
• Dry mouth,
• Photosensitivity reactions (increased skin sensitivity to sunlight),
• Arthralgia (joint pain),
• Myalgia (muscle pain),
• Chest pain,
• Malaise,
• Peripheral oedema,
• Fever,
• Increased blood urea,
• Increased blood creatinine,
• Falls.

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

• Worsening of psoriasis,
• Changes in laboratory parameters: increased liver enzyme levels, elevated serum bilirubin levels,
• Fatigue.

Very rare (may affect up to 1 in 10,000 people):

• Confusion,
• Eosinophilic pneumonia (a rare type of pneumonia),
• Very concentrated urine (dark-coloured), feeling unwell, muscle cramps, confusion and seizures, possibly due to inappropriate secretion of ADH (antidiuretic hormone). If you experience these symptoms, contact your doctor immediately.
• Rhinitis (blocked or runny nose),
• Severe kidney problems,
• Changes in blood parameters, such as reduced numbers of white and red blood cells, lower haemoglobin, reduced platelet count, high blood calcium levels, abnormal liver function.

Not known (frequency cannot be estimated from available data):

• Abnormal ECG pattern,
• Changes in laboratory parameters: low potassium levels, high uric acid levels and high blood sugar levels,
• Decreased vision (myopia),
• Blurred vision,
• Abnormal colour vision,
• Numbness and pain in fingers or toes (Raynaud's phenomenon),
• Decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma),
• If you suffer from systemic lupus erythematosus (a connective tissue disease), this may worsen.

Haematological, renal, hepatic or pancreatic disorders and changes in laboratory parameters (blood tests) may
occur. Your doctor may prescribe laboratory tests to monitor your condition.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Perindopril and Indapamide Zentiva 4 mg+1.25 mg

Keep this medicine out of the sight and reach of children.
Do not store above 30°C.
Do not use this medicine after the expiry date which is stated on the carton and blister after the word
“EXP”. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Perindopril and Indapamide Zentiva 4 mg+1.25 mg contains

• The active substances are perindopril tert-butylamine and indapamide. One tablet contains 4 mg of perindopril tert-butylamine, equivalent to 3.338 mg of perindopril, and 1.25 mg of indapamide.
• The other components are: microcrystalline cellulose, monohydrate lactose, anhydrous colloidal silica, and magnesium stearate.

Description of the appearance of Perindopril and Indapamide Zentiva 4 mg+1.25 mg and contents of the
package
Perindopril and Indapamide Zentiva 4 mg+1.25 mg tablets are white, capsule-shaped tablets, with a break line on both sides, a "+" marked on both sides of the break line, and smooth on the back, with a length of 8.0±0.2 mm and a width of 4.0±0.2 mm.
The tablet can be divided into equal doses.
Tablets are available in blisters of 10, 20, 30 or 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Zentiva Italia S.r.l.
Viale L. Bodio n. 37/B
20158 Milan
Italy

Manufacturer:
Atlantic Pharma – Produções Farmacêuticas SA
Rua da Tapada Grande, 2
Abrunheira, 2710–089 Sintra
Portugal

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

Package leaflet: Information for the user

Perindopril and Indapamide Zentiva 8 mg+2.5 mg tablets

Generic medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Never give it to other people, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Perindopril and Indapamide Zentiva 8 mg+2.5 mg is and what it is used for
2. What you need to know before taking Perindopril and Indapamide Zentiva 8 mg+2.5 mg
3. How to take Perindopril and Indapamide Zentiva 8 mg+2.5 mg
4. Possible side effects
5. How to store Perindopril and Indapamide Zentiva 8 mg+2.5 mg
6. Contents of the pack and other information

1. What Perindopril and Indapamide Zentiva 8 mg+2.5 mg is and what it is used for

Perindopril and Indapamide Zentiva 8 mg+2.5 mg is a combination of two active substances, perindopril and indapamide. It is an antihypertensive medicine used in the treatment of high blood pressure (hypertension).
Perindopril and Indapamide Zentiva 8 mg+2.5 mg is prescribed for patients who are already being treated with perindopril 8 mg and indapamide 2.5 mg as separate tablets; such patients may instead be given one tablet of Perindopril and Indapamide Zentiva 8 mg+2.5 mg containing both active substances.
Perindopril belongs to a class of medicines called ACE inhibitors. These medicines work by dilating blood vessels, making it easier for the heart to pump blood through them.
Indapamide is a diuretic. Diuretics increase the amount of urine produced by the kidneys. However, indapamide differs from other diuretics in that it causes only a slight increase in the amount of urine produced.
Each active substance reduces blood pressure, and together they act to control blood pressure.

2. What you need to know before taking Perindopril and Indapamide Zentiva 8 mg+2.5 mg

Do not take Perindopril and Indapamide Zentiva 8 mg+2.5 mg

• if you are allergic to perindopril or any other ACE inhibitor,
• if you are allergic to indapamide or to any other sulfonamide,
• if you are allergic to any of the other ingredients of this medicine (listed in section 6),
• if you have previously experienced symptoms such as wheezing, swelling of the face or tongue, intense itching, or severe skin rashes related to prior treatment with ACE inhibitors, or if you or a family member has experienced such symptoms under any circumstances (a condition called angioedema),
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren,
• if you have severe liver disease or suffer from a condition called hepatic encephalopathy (a degenerative brain disorder),
• if you have severe kidney disease, particularly with reduced blood flow to the kidneys (renal artery stenosis),
• if you are undergoing dialysis or any type of blood filtration. Depending on the equipment used, treatment with Perindopril and Indapamide Zentiva may not be suitable for you,
• if you have low plasma potassium levels,
• if you suspect you have untreated decompensated heart failure (severe fluid retention, breathing difficulties),
• if you are more than 3 months pregnant. (It is best to avoid Perindopril and Indapamide Zentiva 8 mg+2.5 mg even in the early stages of pregnancy – see section “Pregnancy and Breast-feeding”),
• if you are breastfeeding,
• if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as the risk of angioedema (rapid swelling under the skin, for example in the throat) may increase.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Perindopril and Indapamide Zentiva 8 mg+2.5 mg:

• if you have aortic stenosis (narrowing of the main artery leaving the heart) or hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidneys),
• if you suffer from heart failure or other heart problems,
• if you have kidney problems or are on dialysis,
• if you have abnormally high levels of a hormone in the blood called aldosterone (primary aldosteronism),
• if you have liver problems,
• if you have a collagen disease (skin disease) such as systemic lupus erythematosus (a special type of chronic inflammation) or scleroderma,
• if you suffer from atherosclerosis (hardening of the arteries),
• if you have hyperparathyroidism (overactivity of the parathyroid glands),
• if you suffer from gout,
• if you have diabetes,
• if you are on a low-salt diet or use salt substitutes containing potassium,
• if you are taking lithium or potassium-sparing medicines (spironolactone, triamterene) or potassium supplements, as their use with Perindopril and Indapamide Zentiva 8 mg+2.5 mg should be avoided (see “Taking Perindopril and Indapamide Zentiva 8 mg+2.5 mg with other medicines”),
• if you are elderly,
• if you have experienced photosensitivity reactions,
• if you develop vision changes or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased intraocular pressure and may occur within hours or weeks of taking Perindopril and Indapamide Zentiva. This may lead to permanent vision loss if not treated. If you previously had an allergy to penicillin or sulfonamides, you may be at higher risk of developing one.
• if you are taking any of the following medicines used to treat high blood pressure:
• an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans – for example valsartan, telmisartan, irbesartan), 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 section "Do not take Perindopril and Indapamide Zentiva",
• if you are of African origin, as you may have a higher risk of angioedema and this medicine may be less effective in lowering your blood pressure compared to non-black patients,
• if you are a patient undergoing hemodialysis with high-flux membranes,
• if you are taking any of the following medicines, which increase the risk of angioedema:
• racecadotril (used to treat diarrhoea),
• sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment),
• vildagliptin, a medicine used to treat diabetes.

Angioedema
Angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat with difficulty swallowing or breathing) has been reported in patients treated with ACE inhibitors, including perindopril + indapamide. This may occur at any time during treatment. If you develop such symptoms, stop treatment with Perindopril and Indapamide Zentiva and contact a doctor immediately. See also section 4.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Perindopril and Indapamide Zentiva 8 mg+2.5 mg is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the unborn child if taken during this period (see “Pregnancy and breast-feeding”).
If you are taking Perindopril and Indapamide Zentiva 8 mg+2.5 mg, inform your doctor or medical staff:

• if you are scheduled for anaesthesia and/or surgery,
• if you have recently had diarrhoea or vomiting, or if you are dehydrated,
• if you are scheduled for dialysis or LDL apheresis (blood purification to remove cholesterol using a machine),
• if you are undergoing desensitisation treatment to reduce the effects of an allergy to bee or wasp stings,
• if you are scheduled for a medical examination requiring injection of an iodinated contrast agent (a substance that makes organs such as kidneys or stomach visible on X-rays),
• if you experience vision changes or pain in one or both eyes while taking Perindopril and Indapamide Zentiva. This could be a sign of developing glaucoma, increased pressure in one or both eyes. Stop treatment with Perindopril and Indapamide Zentiva and consult a doctor.

Athletes should be aware that Perindopril and Indapamide Zentiva 8 mg+2.5 mg contains an active substance (indapamide) that may lead to a positive result in anti-doping tests.

Children and adolescents
Perindopril and Indapamide Zentiva 8 mg+2.5 mg must not be given to children or adolescents.

Other medicines and Perindopril and Indapamide Zentiva 8 mg+2.5 mg
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

You must not take Perindopril and Indapamide Zentiva 8 mg+2.5 mg with:

• lithium (used to treat manic disorder and depression),
• aliskiren (a medicine used to treat high blood pressure) if you do not have diabetes or kidney problems,
• potassium-sparing diuretics (such as triamterene, amiloride), potassium salts (including salt substitutes), and other medicines that may increase blood potassium levels (such as heparin, a medicine used to thin the blood to prevent clotting; trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole for bacterial infections),
• estramustine (used in cancer therapy),
• other medicines used to treat high blood pressure: angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers.

Treatment with Perindopril and Indapamide Zentiva 8 mg+2.5 mg may be affected by other medicines. Your doctor may need to adjust your dose and/or take other precautions. Make sure to inform your doctor if you are taking any of these medicines, as special monitoring may be required:

• other medicines for treating high blood pressure, including an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also section "Do not take Perindopril and Indapamide Zentiva 8 mg+2.5 mg" and "Warnings and precautions") or diuretics (medicines that increase urine production by the kidneys),
• potassium-sparing diuretics used in the treatment of heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg daily,
• medicines mainly used to treat diarrhoea (racecadotril) or to prevent rejection after organ transplantation (sirolimus, everolimus, temsirolimus and other medicines belonging to the class of so-called mTOR inhibitors). See section “Warnings and precautions”,
• sacubitril/valsartan (used for long-term treatment of heart failure). See sections "Do not take Perindopril and Indapamide Zentiva 8 mg/2.5 mg” and “Warnings and precautions”,
• anaesthetics,
• iodinated contrast agents,
• moxifloxacin, sparfloxacin (antibiotics: medicines used to treat infections),
• methadone (used to treat addiction),
• procainamide (for treating irregular heartbeat),
• allopurinol (for treating gout),
• mizolastine, terfenadine or astemizole (antihistamines for hay fever or allergies),
• corticosteroids used to treat various conditions including severe asthma and rheumatoid arthritis,
• immunosuppressants used to treat autoimmune diseases or after transplants to prevent rejection (e.g. cyclosporine, tacrolimus),
• injectable erythromycin (an antibiotic),
• halofantrine (used to treat certain types of malaria),
• pentamidine (used to treat pneumonia),
• injectable gold (used to treat rheumatoid polyarthritis),
• vincamine (used to treat symptomatic cognitive disorders in the elderly, including memory loss),
• bepridil (used to treat angina pectoris),
• sultopride (for treating psychosis),
• medicines used to treat heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol),
• cisapride, difemanil (used to treat gastric and digestive problems),
• digoxin or other cardiac glycosides (for treating heart problems),
• baclofen (to treat muscle stiffness in conditions such as multiple sclerosis),
• medicines for treating diabetes such as insulin, metformin or gliptins,
• calcium, including calcium supplements,
• stimulant laxatives (e.g. senna),
• Non-Steroidal Anti-Inflammatory Drugs (e.g. ibuprofen) or high-dose salicylates (e.g. aspirin),
• injectable amphotericin B (for treating serious fungal infections),
• medicines for treating mental disorders such as depression, anxiety, schizophrenia (e.g. tricyclic antidepressants, neuroleptics),
• tetracosactide (for treating Crohn's disease),
• trimethoprim (for treating infections),
• vasodilators including nitrates (substances that widen blood vessels),
• medicines used to treat low blood pressure, shock or asthma (e.g. ephedrine, noradrenaline or adrenaline).

Perindopril and Indapamide Zentiva 8 mg+2.5 mg with food and drink
It is preferable to take Perindopril and Indapamide Zentiva 8 mg+2.5 mg before a meal.

Pregnancy and breast-feeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breast-feeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
Inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Perindopril and Indapamide Zentiva 8 mg+2.5 mg before starting pregnancy or as soon as you know you are pregnant, and will recommend an alternative medicine. Perindopril and Indapamide Zentiva 8 mg+2.5 mg is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the unborn child if taken beyond the third month of pregnancy.

Breast-feeding
Inform your doctor immediately if you are breast-feeding or planning to start breast-feeding. You must not take Perindopril and Indapamide Zentiva 8 mg+2.5 mg while breast-feeding. Your doctor may choose an alternative treatment for you if you wish to breast-feed, especially if your baby is a newborn or was born prematurely.
Inform your doctor immediately.

Driving and using machines
Perindopril and Indapamide Zentiva 8 mg+2.5 mg normally does not affect alertness, but in some patients different reactions such as dizziness or fatigue may occur due to blood pressure reduction. If you experience such symptoms, your ability to drive or operate machinery may be impaired.

Perindopril and Indapamide Zentiva 8 mg+2.5 mg contains lactose monohydrate
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Perindopril and Indapamide Zentiva 8 mg+2.5 mg

Take this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.
The recommended dose is one tablet daily.
Take the tablet preferably in the morning and before a meal.
Swallow the tablet with a glass of water.
The tablet may be divided into equal doses.

If you take more Perindopril and Indapamide Zentiva 8 mg+2.5 mg than you should
If you have taken an excessive amount of tablets, contact your doctor immediately or go immediately to the nearest emergency department.
The most likely effect in case of overdose is a drop in blood pressure. If a marked decrease in blood pressure occurs (associated with nausea, vomiting, cramps, dizziness, drowsiness, confusion, changes in the amount of urine produced by the kidneys), lying down with legs elevated may be helpful.

If you forget to take Perindopril and Indapamide Zentiva 8 mg+2.5 mg
It is important to take the medicine every day, as regular treatment is more effective. However, if you forget to take a dose of Perindopril and Indapamide Zentiva 8 mg+2.5 mg, take the next dose at your usual time.
Do not take a double dose to make up for the forgotten dose.

If you stop taking Perindopril and Indapamide Zentiva 8 mg+2.5 mg
Since treatment for high blood pressure is usually lifelong, you must speak with your doctor before stopping this medicine.

If you have any doubts about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking the medicine immediately and contact your doctor straight away if you experience any of the
following:

• Severe dizziness or fainting due to low blood pressure (common – may affect up to 1 in 10 people),
• Bronchospasm (tightness of the chest, wheezing and shortness of breath) (uncommon – may affect up to 1 in 100 people),
• Swelling of the face, lips, mouth, tongue or throat, difficulty in breathing (angioedema) (see section 2 “Warnings and precautions”) (uncommon – may affect up to 1 in 100 people),
• Severe skin reactions including erythema multiforme (a skin rash that often starts with itchy red patches on the face, arms or legs) or severe rash, hives, redness of the skin all over the body, severe itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome) or other allergic reactions (very rare – may affect up to 1 in 10,000 people),
• Cardiovascular disorders [irregular heartbeat, angina pectoris (pain in the chest, jaw and back caused by physical exertion), heart attack] (very rare – may affect up to 1 in 10,000 people),
• Weakness in arms or legs, or speech problems which could be signs of a possible stroke (very rare – may affect up to 1 in 10,000 people),
• Inflammation of the pancreas which may cause severe abdominal pain and backache accompanied by feeling unwell (very rare – may affect up to 1 in 10,000 people),
• Yellowing of the skin or eyes (jaundice) which may be a sign of hepatitis (very rare – may affect up to 1 in 10,000 people),
• Life-threatening irregular heartbeat (not known – frequency cannot be estimated from the available data),
• Brain disease caused by liver disease (hepatic encephalopathy) (not known – frequency cannot be estimated from the available data).

Undesirable effects in decreasing order of frequency may include:
Common (may affect up to 1 in 10 people):

• Skin reactions in people predisposed to allergies and asthmatic reactions,
• Headache,
• Dizziness,
• Vertigo,
• Tingling,
• Visual disturbances,
• Tinnitus (noise in the ears),
• Cough,
• Shortness of breath (dyspnoea),
• Gastrointestinal disorders (nausea, vomiting, abdominal pain, taste disturbances, dyspepsia or difficulty in digestion, diarrhoea, constipation),
• Allergic reactions (such as skin rashes, itching),
• Muscle cramps,
• Feeling of fatigue.

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

• Mood changes,
• Sleep disorders,
• Urticaria,
• Purpura (small red spots on the skin),
• Blisters in clusters,
• Kidney disorders,
• Impotence,
• Sweating, increased eosinophils (a type of white blood cells),
• Changes in laboratory parameters: high blood potassium levels (reversible upon discontinuation), low blood sodium levels,
• Drowsiness,
• Fainting,
• Palpitations (awareness of heartbeat),
• Tachycardia (fast heartbeat),
• Hypoglycaemia (low blood sugar levels) in diabetic patients,
• Vasculitis (inflammation of blood vessels),
• Dry mouth,
• Photosensitivity reactions (increased skin sensitivity to sunlight),
• Arthralgia (joint pain),
• Myalgia (muscle pain),
• Chest pain,
• Malaise,
• Peripheral oedema,
• Fever,
• Increased blood urea,
• Increased blood creatinine,
• Falls.

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

• Worsening of psoriasis,
• Changes in laboratory parameters: increased liver enzyme levels, elevated serum bilirubin levels,
• Fatigue.

Very rare (may affect up to 1 in 10,000 people):

• Confusion,
• Eosinophilic pneumonia (a rare type of pneumonia),
• Very concentrated urine (dark in colour), sensation or state of malaise, muscle cramps, confusion and seizures, possibly due to inappropriate ADH (antidiuretic hormone) secretion. If you experience these symptoms, contact your doctor immediately.
• Rhinitis (blocked or runny nose),
• Severe kidney problems,
• Changes in blood parameters such as reduced numbers of white and red blood cells, lower haemoglobin, reduced platelet count, high blood calcium levels, abnormal liver function.

Not known (frequency cannot be estimated from the available data):

• Abnormal ECG trace,
• Changes in laboratory parameters: low potassium levels, high uric acid levels and high blood sugar levels,
• Decreased vision (myopia),
• Blurred vision,
• Abnormal colour vision,
• Numbness and pain in fingers or toes (Raynaud's phenomenon),
• Decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma),
• If you suffer from systemic lupus erythematosus (a connective tissue disease), this may worsen.

Haematological, renal, hepatic or pancreatic disorders and changes in laboratory parameters (blood tests) may occur. Your doctor may prescribe laboratory tests to monitor your condition.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Perindopril and Indapamide Zentiva 8 mg+2.5 mg

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the carton and blister after the word "EXP". The expiry date refers to the last day of the month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Perindopril and Indapamide Zentiva 8 mg+2.5 mg contains

• The active substances are perindopril tert-butylamine and indapamide. One tablet contains 8 mg of perindopril tert-butylamine, equivalent to 6.676 mg of perindopril, and 2.5 mg of indapamide.
• The other components are: microcrystalline cellulose, monohydrate lactose, anhydrous colloidal silica and magnesium stearate.

Description of the appearance of Perindopril and Indapamide Zentiva 8 mg+2.5 mg and contents of the pack
Perindopril and Indapamide Zentiva 8 mg+2.5 mg are circular, white to almost white tablets with a break line on one side, with a length of 8.0±0.2 mm.
The tablets are available in blisters in packs of 30 tablets.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Zentiva Italia S.r.l.
Viale L. Bodio n. 37/B
20158 Milano
Italy
Manufacturer:
Atlantic Pharma – Produções Farmacêuticas SA
Rua da Tapada Grande, 2
Abrunheira, 2710 – 089 Sintra
Portugal
This medicinal product is authorized in the European Economic Area Member States under the following names: