Perindopril + indapamide krka

Package leaflet: Information for the patient

Perindopril + Indapamide Krka, 8 mg + 2.5 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 further questions, 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 someone else, even if their symptoms are similar.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of 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 for the treatment of high blood pressure (arterial hypertension).

Why Perindopril + Indapamide Krka is used
Perindopril belongs to a group of medicines called angiotensin-converting enzyme (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. 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 lowers blood pressure, and their combined action improves blood pressure control.

Perindopril + Indapamide Krka is intended for patients who have previously been treated with perindopril at a dose of 8 mg and indapamide at a dose of 2.5 mg as separate medicines. Such patients may take one tablet of Perindopril + Indapamide Krka 8 mg + 2.5 mg, which contains both active substances, instead of taking separate tablets.

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 sulphonamide-type medicine; or to any of the other ingredients of this medicine (listed in section 6);
• If the patient has previously experienced the following symptoms while taking ACE inhibitors: wheezing, facial or tongue swelling, intense itching, or severe skin rashes; or if such symptoms have occurred in the patient or a family member under any circumstances (a condition known as angioedema);
• In patients with severe liver disease or hepatic encephalopathy (brain function disorders);
• In patients with severe kidney disease causing reduced blood flow to the kidneys (renal artery stenosis);
• If the patient is undergoing dialysis or another form of blood filtration. Depending on the equipment used, Perindopril + Indapamide Krka may not be suitable;
• In cases of abnormally high or low blood potassium levels;
• In patients with suspected untreated or uncontrolled heart failure (symptoms may include significant 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, as this increases the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat).

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

• If the patient has aortic valve stenosis (narrowing of the main artery leaving the heart) or hypertrophic cardiomyopathy (a heart muscle disorder) 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 disease 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 disease;
• If the patient has connective tissue diseases (skin disorders), 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 using 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, which may cause difficulty 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.

Your doctor may recommend regular monitoring of kidney function, blood pressure, and blood
electrolyte levels (e.g. potassium).
See also the 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 your doctor without delay. See also section 4.
Always inform your doctor if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. 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 "Pregnancy and breastfeeding").
You should also inform your doctor or medical staff if:

• You are planning to have anaesthesia and/or surgery,
• You have recently had diarrhoea, vomiting or dehydration,
• You are scheduled for dialysis or LDL cholesterol apheresis (a procedure to remove cholesterol from the blood using a special device),
• You are undergoing desensitisation treatment for bee or wasp venom,
• You are scheduled for a diagnostic procedure involving intravenous administration of iodine-containing contrast agents (substances that help visualise organs such as kidneys or stomach on X-ray images),
• You experience vision disturbances or eye pain in one or both eyes during treatment with Perindopril + Indapamide Krka. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive fluid accumulation 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 sulphonamides or penicillin may be at higher risk of developing this condition. Stop taking Perindopril + Indapamide Krka and contact your doctor.

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 who do not have diabetes or kidney dysfunction;
• Potassium supplements (including salt substitutes), potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium salts, or 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 in cancer treatment);
• 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 in heart failure treatment: eplerenone and spironolactone at doses of 12.5 mg to 50 mg per day;
• A medicine containing sacubitril and valsartan (used in chronic heart failure treatment). See sections "When not to use Perindopril + Indapamide Krka" and "Warnings and precautions".
• Anaesthetic medicines;
• 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 to 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 lung infection),
• Vinpocetine (used for symptomatic cognitive disorders in the elderly, including memory loss),
• Bepridil (used for angina),
• Medicines used for heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, bretylium),
• Cisapride, difenoxin (used for gastrointestinal disorders),
• Digoxin or other cardiac glycosides (used to treat heart conditions),
• Baclofen (used for muscle stiffness in conditions such as multiple sclerosis),
• Antidiabetic medicines, such as insulin, metformin or gliptins,
• Calcium, including calcium supplements,
• Stimulant laxatives (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 psychiatric 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 joint inflammation), e.g. sodium aurothiomalate,
• A medicine commonly used to treat diarrhoea (racecadotril),
• Medicines 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 a dose adjustment and/or 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 you suspect or plan to become pregnant, 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 a planned pregnancy or as soon as possible after pregnancy is confirmed, and will recommend an alternative medicine. Perindopril + Indapamide Krka is not recommended in 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 an alternative medicine if you wish to breastfeed.
Driving and operating machinery
Perindopril + Indapamide Krka generally does not affect alertness, but in some patients, individual reactions such as dizziness or weakness due to low blood pressure may occur. 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; therefore, it can essentially be considered "sodium-free".

3. How to use Perindopril + Indapamide Krka

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

Taking more Perindopril + Indapamide Krka than prescribed
If you take too many tablets, contact your doctor immediately or go to the nearest hospital emergency department.
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 the amount of urine produced by the kidneys), lie down flat 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 treatment with Perindopril + Indapamide Krka
Since treatment for high blood pressure usually lasts for life, you should consult your doctor before stopping the treatment.
If you have any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If the patient experiences any of the following adverse reactions, which may be
serious, treatment with this medicine must be discontinued immediately and medical advice must be sought without delay:

• 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 section 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 the 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 severe 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 with a tendency to allergic or asthmatic reactions, headache, visual disturbances, dizziness, fatigue (asthenia), tinnitus, vertigo (spinning sensation), tingling and numbness, dyspnoea, 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 tiredness, low blood potassium levels.

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

• mood changes, sleep disturbances, depression, urticaria, purpura (small 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, transient after discontinuation of treatment, low blood sodium levels, which may lead to dehydration and low blood pressure; drowsiness, fainting, palpitations (awareness of heartbeat), tachycardia (rapid heart rate), 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), symptoms of the disease 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 plasma calcium levels, low blood chloride levels, low blood magnesium levels, reduced or absent urine output, sudden redness of the face and neck, acute kidney failure;
• dark-coloured 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 blood cell and red blood cell counts, decreased haemoglobin concentration, decreased haematocrit, decreased platelet count, liver function disorders.

Not known (frequency 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, myopia, blurred vision, visual impairment or eye pain due to
  elevated 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 the 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, the patient should inform their doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring of 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 to provide more information on the safety of the medicine.

5. How to store Perindopril + Indapamide Krka

Keep this medicine out of the 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 30 °C.
Store in the original packaging to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Package contents and other information

What Perindopril + Indapamide Krka contains

• The active substances are perindopril with tert-butylamine and indapamide. Each tablet contains 8 mg of perindopril with tert-butylamine, equivalent to 6.68 mg of perindopril and 2.5 mg of indapamide.
• Other ingredients: calcium chloride dihydrate, lactose monohydrate, crospovidone, microcrystalline cellulose, sodium hydrogen carbonate, colloidal anhydrous 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 a score line on one side. The score line is intended only to facilitate breaking the tablet for ease of swallowing and does not ensure equal division of the dose.
Pack sizes: 14, 20, 28, 30, 50, 56, 60, 90 or 100 tablets in blisters packed 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 European Economic Area countries, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Tel. 22 57 37 500