Perindopril + indapamide krka

Package leaflet: Information for the patient

Perindopril + Indapamide Krka, 4 mg + 1.25 mg, tablets
tert-butylamini perindoprilum + indapamidum
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Perindopril + Indapamide Krka is and what it is used for

What Perindopril + Indapamide Krka is
Perindopril + Indapamide Krka is a combination of two active substances, perindopril and indapamide. Perindopril + Indapamide Krka is an antihypertensive medicine used in the treatment of high blood pressure (hypertension).

What Perindopril + Indapamide Krka is used for
Perindopril belongs to a group of medicines called angiotensin-converting enzyme inhibitors (ACE inhibitors). These medicines work by dilating blood vessels, which makes it easier for the heart to pump blood through them. Indapamide is a diuretic medicine. 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 urine production. Each of the active substances reduces blood pressure, and their combined action improves blood pressure control.

2. Important information before using Perindopril + Indapamide Krka

When not to use Perindopril + Indapamide Krka:

• If the patient is allergic to perindopril or any other ACE inhibitor; or to indapamide or any other sulfonamide-type drug; or to any of the other ingredients of this medicine (listed in section 6);
• If the patient previously experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin rash while taking ACE inhibitors; or if such symptoms occurred in the patient or a family member under any other circumstances (a condition called angioedema);
• In patients with severe liver disease or hepatic encephalopathy (brain function disorders);
• If the patient has severe kidney disease causing reduced blood flow to the kidneys (renal artery stenosis);
• If the patient is undergoing dialysis or other blood filtration methods. Depending on the equipment used, Perindopril + Indapamide Krka may not be suitable;
• In case of increased or decreased blood potassium levels;
• In patients with suspected untreated or uncontrolled heart failure (symptoms may include fluid retention and breathing difficulties);
• After the 3rd month of pregnancy (use of Perindopril + Indapamide Krka is also not recommended in early pregnancy – see "Pregnancy and breastfeeding");
• If the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medicine containing aliskiren;
• If the patient has taken or is currently using sacubitril with valsartan, a medicine used to treat certain types of chronic (long-term) heart failure in adults, because the risk of angioedema (rapid swelling of tissues under the skin, e.g. in the throat) increases.

Warnings and precautions
Before starting treatment with Perindopril + Indapamide Krka, discuss the following with your doctor or pharmacist:

• If the patient has aortic valve stenosis (narrowing of the main artery valve leaving the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the artery supplying blood to the kidney);
• If the patient has heart failure or any other heart conditions;
• If the patient has kidney diseases or is undergoing dialysis;
• If the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• If the patient has liver diseases;
• If the patient has connective tissue diseases (skin diseases), such as systemic lupus erythematosus or systemic sclerosis;
• If the patient has atherosclerosis (hardening of the arterial walls);
• If the patient has hyperparathyroidism (overactivity of the parathyroid glands);
• If the patient has gout;
• If the patient has diabetes;
• If the patient is on a low-salt diet or uses salt substitutes containing potassium;
• If the patient is taking lithium or potassium-sparing diuretics (spironolactone, triamterene) – their use should be avoided with Perindopril + Indapamide Krka (see "Perindopril + Indapamide Krka and other medicines");
• If the patient is elderly;
• If the patient has previously experienced photosensitivity reactions;
• If the patient develops a severe allergic reaction with swelling of the face, lips, mouth, tongue, or throat, causing difficulty in swallowing or breathing (angioedema) – swelling may occur at any time during treatment. If such symptoms occur, stop treatment immediately and contact a doctor without delay;
• If the patient is taking any of the following medicines used to treat high blood pressure:
  • An angiotensin II receptor antagonist (AIIRA), also known as a sartan – for example, valsartan, telmisartan, irbesartan, especially if the patient has kidney problems related to diabetes,
  • Aliskiren. The doctor may recommend regular monitoring of kidney function, blood pressure, and blood electrolyte levels (e.g. potassium). See also section "When not to use Perindopril + Indapamide Krka".
• If the patient is of Black race – in such cases, there may be a higher risk of angioedema and the medicine may be less effective in lowering blood pressure compared to patients of other races;
• If the patient is undergoing dialysis using high-flux membranes;
• If the patient is taking any of the following medicines, which increase the risk of angioedema (rapid swelling of the skin, e.g. in the throat):
  • Racecadotril (used to treat diarrhoea),
  • Sirolimus, everolimus, temsirolimus, and other medicines belonging to the so-called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment),
  • Linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the group of drugs called gliptins (used in diabetes treatment).

Angioedema
Angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat, and difficulty swallowing or breathing) has been reported in patients treated with ACE inhibitors, including Perindopril + Indapamide Krka. This reaction may occur at any time during treatment. If such symptoms occur, stop taking Perindopril + Indapamide Krka immediately and contact a doctor without delay. See also section 4.
It is essential to inform the doctor about pregnancy, suspected pregnancy, or planned pregnancy. Use of Perindopril + Indapamide Krka is not recommended during the first trimester of pregnancy and must not be taken after the 3rd month of pregnancy, as it may seriously harm the unborn child (see "Pregnacy and breastfeeding").
Inform your doctor or medical staff if you are:

• Planning anaesthesia and/or surgery,
• Recently had diarrhoea, vomiting, or dehydration,
• Planning dialysis or LDL cholesterol apheresis (a procedure to remove cholesterol from the blood using a special device),
• Planning allergen immunotherapy for bee or wasp venom,
• Planning a diagnostic procedure involving intravenous administration of iodine-containing contrast agents (substances that help visualize organs such as kidneys or stomach on X-ray images),
• Experiencing vision disturbances or pain in one or both eyes while taking Perindopril + Indapamide Krka. These may be symptoms of fluid accumulation in the avascular membrane surrounding the eye (excessive fluid buildup between choroid and sclera) or glaucoma, increased pressure in one or both eyes – which may occur from several hours to weeks after taking Perindopril + Indapamide Krka. Patients with a history of allergy to sulfonamides or penicillin may be at higher risk of developing this condition. Stop using Perindopril + Indapamide Krka and consult a doctor immediately.

The medicine contains an active substance (indapamide) that may lead to positive results in doping tests.
Children and adolescents
Perindopril + Indapamide Krka must not be used in children and adolescents.
Perindopril + Indapamide Krka and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Avoid taking Perindopril + Indapamide Krka with:

• Lithium (used to treat depression),
• Aliskiren (a medicine used to treat high blood pressure) in patients without diabetes or kidney dysfunction;
• Potassium supplements (including salt substitutes), potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium salts, and other medicines that may increase

potassium levels in the body (such as heparin, a medicine used to thin the blood to prevent clots; trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole, used for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ rejection);

• Estramustine (used to treat cancer);
• Other medicines used to treat high blood pressure: ACE inhibitors and angiotensin II receptor antagonists.

Other medicines may affect treatment with Perindopril + Indapamide Krka. Inform your doctor if you are taking any of the following medicines, as special care may be needed:

• Other medicines used to treat high blood pressure; including angiotensin II receptor antagonists (AIIRAs) or aliskiren (see also sections "When not to use Perindopril + Indapamide Krka" and "Warnings and precautions"), or diuretics (medicines that increase urine output by the kidneys);
• Potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses from 12.5 mg to 50 mg per day;
• A combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to use Perindopril + Indapamide Krka" and "Warnings and precautions".
• Anaesthetics;
• Iodine-containing contrast agents;
• Procainamide (used to treat heart rhythm disorders),
• Allopurinol (used to treat gout),
• Terfenadine or astemizole, mizolastine (antihistamines used for hay fever or allergies),
• Corticosteroids used to treat various diseases, including severe asthma and rheumatoid arthritis,
• Immunosuppressive medicines used to treat autoimmune diseases or prevent organ rejection after transplantation (e.g. cyclosporine, tacrolimus),
• Anticancer medicines,
• Intravenous erythromycin, moxifloxacin, sparfloxacin (antibiotics),
• Halofantrine (used for certain types of malaria),
• Pentamidine (used for pneumonia),
• Vinpocetine (used for cognitive disorders in the elderly, including memory loss),
• Bepridil (used for angina pectoris),
• Medicines used for heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, bretylium),
• Cisapride, difenamid (used to treat gastrointestinal disorders),
• Digoxin or other cardiac glycosides (used to treat heart diseases),
• Baclofen (used for muscle stiffness in diseases such as multiple sclerosis),
• Antidiabetic medicines, such as insulin, metformin, or gliptins,
• Calcium, including calcium supplements,
• Laxatives stimulating peristalsis (e.g. senna),
• Non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or salicylates in high doses (e.g. acetylsalicylic acid),
• Intravenous amphotericin B (used for severe fungal infections),
• Medicines used for mental disorders such as depression, anxiety, schizophrenia [e.g. tricyclic antidepressants, neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol)],
• Tetracosactide (used for Crohn's disease),
• Vasodilating medicines, including nitrates,
• Intravenous gold (used for arthritis), e.g. sodium aurothiomalate,
• A medicine most commonly used to treat diarrhoea (racecadotril),
• Medicines most commonly used to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, or other medicines belonging to the so-called mTOR inhibitors). See section "Warnings and precautions",
• Medicines used to treat low blood pressure, shock, or asthma (e.g. ephedrine, noradrenaline, or adrenaline).

Your doctor may recommend changing the dose and/or taking additional precautions:

• If the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "When not to use Perindopril + Indapamide Krka" and "Warnings and precautions").

Perindopril + Indapamide Krka with food and drink
It is recommended to take Perindopril + Indapamide Krka before a meal.
Pregnancy and breastfeeding
During pregnancy, breastfeeding, or if pregnancy is suspected or planned, consult your doctor or pharmacist before using this medicine.
Pregnancy
Inform your doctor if you are pregnant, suspect pregnancy, or plan to become pregnant. Your doctor will usually advise stopping Perindopril + Indapamide Krka before planned pregnancy or as soon as possible after pregnancy is confirmed, and will recommend an alternative medicine. Use of Perindopril + Indapamide Krka is not recommended during early pregnancy and must not be taken after the 3rd month of pregnancy, as it may have very harmful effects on the developing baby if used during this period.
Breastfeeding
Inform your doctor if you are breastfeeding or plan to breastfeed. Perindopril + Indapamide Krka is not recommended during breastfeeding, and your doctor may prescribe another medicine if you wish to breastfeed.
Driving and operating machinery
Perindopril + Indapamide Krka usually does not affect alertness, but some patients may experience individual reactions such as dizziness or weakness due to lowered blood pressure. If such symptoms occur, the ability to drive or operate machinery may be impaired.
Perindopril + Indapamide Krka contains lactose and sodium
If the patient has an intolerance to certain sugars, consult a doctor before starting this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet and can therefore be considered essentially "sodium-free".

3. How to take Perindopril + Indapamide Krka

This medicine should always be taken exactly as prescribed by your doctor or pharmacist.
If in doubt, consult your doctor or pharmacist.
The recommended dose is one tablet once daily.
Your doctor may decide to adjust the dosage in case of concomitant kidney function disorders.
It is recommended to take one tablet in the morning, before a meal.
Swallow the tablet with a glass of water.

Taking more Perindopril + Indapamide Krka than prescribed
If you have taken too many tablets, contact your doctor immediately or go to the emergency department of the nearest hospital.
The most likely symptom of overdose is low blood pressure.
In case of a significant drop in blood pressure (accompanied by nausea, vomiting, cramps, dizziness, drowsiness, disorientation, or changes in urine output), lie down on your back with your legs raised above the level of your torso.

Missing a dose of Perindopril + Indapamide Krka
It is important to take the medicine every day, as the effectiveness of hypertension treatment depends on regular use. However, if you miss a dose of Perindopril + Indapamide Krka, take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

Stopping Perindopril + Indapamide Krka
Since treatment for high blood pressure usually lasts for life, you should consult your doctor before stopping the medication.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
If the patient experiences any of the following adverse reactions, which may be
severe, stop taking this medicine and contact a doctor immediately:

• severe dizziness or fainting due to low blood pressure (common – may occur in less than 1 in 10 patients);
• bronchospasm (feeling of tightness in the chest, wheezing and shortness of breath; uncommon – may occur in less than 1 in 100 patients);
• swelling of the face, lips, mouth, tongue or throat, difficulty breathing – sudden allergic reaction with breathlessness, rash (angioedema, see section “Warnings and precautions” in point 2); uncommon – may occur in less than 1 in 100 patients;
• severe skin reactions, including erythema multiforme (skin rash often starting with red, itchy spots on the face, arms or legs) or severe skin rash, urticaria, redness of the entire skin surface, intense itching, blistering, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions (very rare – may occur in less than 1 in 10,000 patients);
• cardiovascular disorders (heart rhythm disturbances, angina pectoris (chest pain radiating to the jaw and back, caused by physical exertion), myocardial infarction); very rare – may occur in less than 1 in 10,000 patients;
• weakness of arms or legs, or speech disturbances, which may be signs of stroke (very rare – may occur in less than 1 in 10,000 patients);
• pancreatitis, which may cause severe upper abdominal pain radiating to the back and general malaise (very rare – may occur in less than 1 in 10,000 patients);
• yellowing of the skin or eyes (jaundice), which may be a sign of liver inflammation (very rare – may occur in less than 1 in 10,000 patients);
• life-threatening heart rhythm disturbances (frequency unknown);
• brain disease caused by liver disease (hepatic encephalopathy; frequency unknown);
• muscle weakness, cramps, tenderness or muscle pain, particularly if the patient also feels unwell or has a high temperature, which may be due to abnormal muscle breakdown (frequency unknown).

The following adverse reactions have been reported:
Common (may occur in less than 1 in 10 patients):

• skin reactions in patients prone to allergic and asthmatic reactions, headache, visual disturbances, dizziness, asthenia (weakness), tinnitus, vertigo (spinning sensation), prickling and tingling sensations, shortness of breath, cough, gastrointestinal disorders (nausea, epigastric pain, loss of appetite, vomiting, abdominal pain, taste disturbances, dryness of the oral mucosa, dyspepsia, diarrhoea, constipation), muscle cramps, allergic reactions (such as skin rashes, itching), feeling of fatigue, low blood potassium levels.

Uncommon (may occur in less than 1 in 100 patients):

• mood changes, sleep disturbances, depression, urticaria, purpura (red spots on the skin), clusters of blisters, kidney function disorders, excessive sweating, impotence (inability to achieve or maintain erection), erectile dysfunction, increased eosinophil count (a type of white blood cell), changes in laboratory test results: high blood potassium levels, which may resolve after discontinuation of treatment, low blood sodium levels, which may cause dehydration and low blood pressure, drowsiness, fainting, palpitations (awareness of heartbeat), tachycardia (rapid heartbeat), hypoglycaemia (very low blood sugar levels), vasculitis (inflammation of blood vessels), photosensitivity reactions (increased skin sensitivity to sunlight), joint pain, muscle pain, chest pain, malaise, peripheral oedema, fever, increased blood urea levels, increased blood creatinine levels, falls;
• if the patient has systemic lupus erythematosus (a type of collagenosis), disease symptoms may worsen.

Rare (may occur in less than 1 in 1,000 patients):

• exacerbation of psoriasis, changes in laboratory test results: increased liver enzyme activity, high serum bilirubin levels, increased calcium levels in plasma, low blood chloride levels, low blood magnesium levels, reduced or absent urine output, sudden redness of the face and neck, acute kidney failure,
• dark urine, nausea or vomiting, muscle cramps, disorientation and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion).

Very rare (may occur in less than 1 in 10,000 patients):

• confusion, eosinophilic pneumonia (a rare form of pneumonia), nasal obstruction or rhinitis (inflammation of the nasal mucosa), blood test abnormalities such as decreased white and red blood cell counts, decreased haemoglobin concentration, decreased haematocrit, decreased platelet count, liver function disorders.

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

• abnormal heart function detected in ECG examination, changes in laboratory test results: high uric acid levels and high blood glucose levels, short-sightedness, blurred vision, visual impairment or eye pain due to increased pressure (possible symptoms of fluid accumulation in the avascular membrane surrounding the eye – excessive fluid accumulation between the choroid and sclera – or acute angle-closure glaucoma),
• cyanosis, numbness and pain in fingers or toes (Raynaud's phenomenon).

Blood, kidney, liver or pancreas disorders and changes in laboratory test results (blood tests) may occur. The doctor may recommend blood tests to monitor the patient's health.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Perindopril + Indapamide Krka

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Do not store above 25 °C.
Store in the original packaging to protect from moisture.
Medicines must not be disposed of via the sewage system or in household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Perindopril + Indapamide Krka contains

• The active substances are perindopril with tert-butylamine and indapamide. Each tablet contains 4 mg of perindopril with tert-butylamine, equivalent to 3.34 mg of perindopril, and 1.25 mg of indapamide.
• Other components: calcium chloride hexahydrate, lactose monohydrate, crospovidone, microcrystalline cellulose, sodium bicarbonate, colloidal hydrated silica, magnesium stearate. See section 2 "Perindopril + Indapamide Krka contains lactose and sodium".

What Perindopril + Indapamide Krka looks like and contents of the pack
White to almost white, round, slightly biconvex tablets with bevelled edges and a division line on one side.
The division line on the tablet is intended only to facilitate breaking for ease of swallowing and does not ensure equal dosing.
Pack sizes: 14, 20, 28, 30, 50, 56, 60, 90 or 100 tablets in blister packs contained in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

For further information on product names in other countries of the European Economic Area, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5 Street
02-235 Warsaw, Poland
Tel. 22 57 37 500