Perindopril + Indapamide Krka

Package Leaflet: Information for the Patient

Perindopril + Indapamide Krka, 4 mg + 1.25 mg, Tablets

tert-Butylamine Perindopril + Indapamide

Read the Package Leaflet Carefully Before Taking the Medication, as it Contains Important Information for the Patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medication has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is Perindopril + Indapamide Krka and What is it 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. Package Contents and Other Information

1. What is Perindopril + Indapamide Krka and What is it Used For

What is Perindopril + Indapamide Krka

Perindopril + Indapamide Krka is a combination of two active substances, perindopril and indapamide. Perindopril + Indapamide Krka is an antihypertensive medication used to treat high blood pressure (hypertension).

What is Perindopril + Indapamide Krka Used For

Perindopril belongs to a group of medications called angiotensin-converting enzyme inhibitors (ACE inhibitors). The mechanism of action of these medications involves dilating blood vessels, making it easier for the heart to pump blood through them. Indapamide is a diuretic. Diuretics increase the amount of urine excreted by the kidneys. However, indapamide differs from other diuretics in that it only causes a slight increase in urine production. Each of the active substances lowers blood pressure, and their combined effect improves blood pressure control.

2. Important Information Before Taking Perindopril + Indapamide Krka

When Not to Take Perindopril + Indapamide Krka:

• If the patient is allergic to perindopril or any other ACE inhibitor; or to indapamide or any other sulfonamide or to any of the other ingredients of this medication (listed in section 6);
• If the patient has experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin rashes while taking ACE inhibitors in the past;
• In patients with severe liver disease or hepatic encephalopathy (liver dysfunction);
• If the patient has severe kidney disease that reduces blood flow to the kidneys (renal artery stenosis);
• If the patient is undergoing dialysis or blood filtration using a method other than hemodialysis. Depending on the device used, Perindopril + Indapamide Krka may not be suitable for the patient;
• In case of increased or decreased potassium levels in the blood;
• In patients with suspected untreated or uncontrolled heart failure (symptoms may include water retention and breathing difficulties);
• Above 3 months of pregnancy (it is also recommended to avoid taking Perindopril + Indapamide Krka in early pregnancy - see "Pregnancy and Breastfeeding");
• If the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medication containing aliskiren;
• If the patient has taken or is currently taking sacubitril with valsartan, a medication used to treat a certain type of chronic heart failure in adults, as the risk of angioedema (rapid swelling of tissues under the skin, such as the throat) increases.

Warnings and Precautions

Before starting treatment with Perindopril + Indapamide Krka, discuss it with your doctor or pharmacist:

• if the patient has aortic stenosis (narrowing of the main artery valve) or hypertrophic cardiomyopathy (heart muscle disease) or renal artery stenosis (narrowing of the artery supplying the kidney);
• if the patient has heart failure or any other heart disease;
• if the patient has kidney disease or is undergoing dialysis;
• if the patient has an abnormally high level of a hormone called aldosterone in the blood (primary aldosteronism);
• if the patient has liver disease;
• 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 arteries);
• if the patient has hyperparathyroidism (overactive 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) - avoid taking them with Perindopril + Indapamide Krka (see "Perindopril + Indapamide Krka and Other Medications");
• if the patient is elderly;
• if the patient has had allergic reactions to light;
• if the patient has had a severe allergic reaction with swelling of the face, lips, mouth, tongue, or throat, which can cause difficulty swallowing or breathing (angioedema) - swelling can occur at any time during treatment. If such symptoms occur, discontinue treatment and consult a doctor immediately;
• if the patient is taking any of the following medications used to treat high blood pressure:
• angiotensin II receptor antagonist (AIIRA), also known as a sartan - e.g., valsartan, telmisartan, irbesartan, especially if the patient has kidney dysfunction related to diabetes;
• aliskiren. The doctor may recommend regular monitoring of kidney function, blood pressure, and electrolyte levels (e.g., potassium) in the blood. See also the subsection "When Not to Take Perindopril + Indapamide Krka".
• if the patient is black - in this case, there may be a higher risk of angioedema, and the medication may be less effective in lowering blood pressure than in patients of other races;
• if the patient is undergoing dialysis using a high-flux membrane;
• if the patient is taking any of the following medications, which increase the risk of angioedema (rapid swelling of tissues under the skin, such as the throat):
• racecadotril (used to treat diarrhea),
• sirolimus, everolimus, temsirolimus, and other medications belonging to the so-called mTOR inhibitors (used to prevent organ rejection and treat cancer),
• linagliptin, saxagliptin, sitagliptin, wildagliptin, and other medications belonging to the group of medications called gliptins (used to treat diabetes).

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 can occur at any time during treatment. If the patient experiences such symptoms, discontinue Perindopril + Indapamide Krka and consult a doctor immediately. See also section 4.
It is essential to inform the doctor about pregnancy, suspected pregnancy, or planning pregnancy. The doctor will usually recommend stopping Perindopril + Indapamide Krka before planned pregnancy or as soon as possible after pregnancy is confirmed and recommend taking a different medication instead of Perindopril + Indapamide Krka. It is not recommended to take Perindopril + Indapamide Krka in early pregnancy and should not be taken after 3 months of pregnancy, as it can have a very harmful effect on the development of the fetus if taken during this period of pregnancy.
Also, inform the doctor or medical staff about taking Perindopril + Indapamide Krka in the following situations:

• planned anesthesia and/or surgery,
• recently experienced diarrhea, vomiting, or dehydration,
• planned dialysis or LDL cholesterol apheresis (a procedure to remove cholesterol from the blood using a special device),
• planned desensitization treatment for wasp or bee stings,
• planned diagnostic procedure involving intravenous administration of iodine-containing contrast agents (a substance that allows organs such as the kidneys or stomach to be visible on X-ray images),
• if vision disturbances or eye pain occur during treatment with Perindopril + Indapamide Krka. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive accumulation of fluid between the choroid and sclera) or glaucoma, increased pressure in one or both eyes - they can occur within a few hours to weeks after taking Perindopril + Indapamide Krka. Patients with a history of sulfonamide or penicillin allergy may be more prone to developing this condition. Discontinue Perindopril + Indapamide Krka and consult a doctor.

The medication contains the active substance indapamide, which may give a positive result in anti-doping tests.

Children and Adolescents

Perindopril + Indapamide Krka should not be used in children and adolescents.

Perindopril + Indapamide Krka and Other Medications

Tell your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you plan to take.
Avoid taking Perindopril + Indapamide Krka with:

• lithium (used to treat depression),
• aliskiren (a medication 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 medications that may increase potassium levels in the body (such as heparin, a medication used to thin blood to prevent clots; trimethoprim and cotrimoxazole, also known as trimethoprim/sulfamethoxazole, used to treat bacterial infections; cyclosporine, an immunosuppressive medication used to prevent organ rejection);

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

• other medications used to treat high blood pressure; including angiotensin II receptor antagonists (AIIRA) or aliskiren (see also the subsections "When Not to Take Perindopril + Indapamide Krka" and "Warnings and Precautions"), or diuretics (medications that increase urine production);
• potassium-sparing medications used to treat heart failure: eplerenone and spironolactone in doses of 12.5 mg to 50 mg per day;
• a combination medication containing sacubitril and valsartan (used to treat chronic heart failure). See the subsections "When Not to Take Perindopril + Indapamide Krka" and "Warnings and Precautions".
• anesthetics;
• iodine-containing contrast agents;
• procainamide (used to treat heart rhythm disorders),
• allopurinol (used to treat gout),
• terfenadine or astemizole, mizolastine (antihistamines used to treat hay fever or allergies),
• corticosteroids used to treat various diseases, including severe asthma and rheumatoid arthritis,
• immunosuppressive medications used to treat autoimmune diseases or prevent organ rejection (e.g., cyclosporine, tacrolimus),
• anticancer medications,
• intravenous erythromycin, moxifloxacin, sparfloxacin (antibiotics),
• halofantrine (used to treat certain types of malaria),
• pentamidine (used to treat pneumonia),
• vincamine (used to treat cognitive disorders in the elderly, including memory loss),
• bepridil (used to treat angina pectoris),
• medications used to treat heart rhythm disorders (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, bretylium),
• cisapride, difemanil (used to treat gastrointestinal disorders), digoxin or other cardiac glycosides (used to treat heart conditions),
• baclofen (used to treat muscle stiffness in conditions such as multiple sclerosis),
• antidiabetic medications, such as insulin, metformin, or gliptins,
• calcium, including calcium supplements,
• laxatives that stimulate peristalsis (e.g., senna),
• nonsteroidal anti-inflammatory medications (e.g., ibuprofen) or salicylates in high doses (e.g., acetylsalicylic acid),
• amphotericin B administered intravenously (used to treat severe fungal infections),
• medications used to treat mental disorders, such as depression, anxiety, schizophrenia [e.g., tricyclic antidepressants, neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol)],
• tetracosactide (used to treat Crohn's disease),
• vasodilators, including nitrates,
• gold administered intravenously (used to treat arthritis), e.g., aurothioglucose sodium,
• a medication commonly used to treat diarrhea (racecadotril),
• medications commonly used to prevent organ rejection (sirolimus, everolimus, temsirolimus, or other medications belonging to the so-called mTOR inhibitors). See the subsection "Warnings and Precautions",
• medications used to treat low blood pressure, shock, or asthma (e.g., ephedrine, norepinephrine, or epinephrine).

The doctor may recommend changing the dose and/or taking other precautions:

• if the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also the subsections "When Not to Take 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

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medication.
Pregnancy
Inform your doctor about pregnancy, suspected pregnancy, or planning pregnancy. The doctor will usually recommend stopping Perindopril + Indapamide Krka before planned pregnancy or as soon as possible after pregnancy is confirmed and recommend taking a different medication instead of Perindopril + Indapamide Krka. It is not recommended to take Perindopril + Indapamide Krka in early pregnancy and should not be taken after 3 months of pregnancy, as it can have a very harmful effect on the development of the fetus if taken during this period of pregnancy.
Breastfeeding
Inform your doctor about breastfeeding or intending to breastfeed. Perindopril + Indapamide Krka is not recommended during breastfeeding, and the doctor may prescribe a different medication if the patient wishes to breastfeed.

Driving and Operating Machines

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 machines may be impaired.

Perindopril + Indapamide Krka Contains Lactose and Sodium

If the patient has an intolerance to some sugars, they should consult their doctor before taking this medication.
This medication contains less than 1 mmol of sodium (23 mg) per tablet, which means it is essentially "sodium-free".

3. How to Take Perindopril + Indapamide Krka

Always take this medication exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.
The recommended dose is one tablet once daily.
The doctor may decide to adjust the dosage in case of co-existing kidney function disorders.
It is recommended to take one tablet in the morning, before a meal.
Swallow the tablet with a glass of water.

Overdose of Perindopril + Indapamide Krka

In case of taking too many tablets, immediately contact a doctor or go to the emergency department of the nearest hospital. The most likely symptom of overdose is low blood pressure.
In case of significantly lowered blood pressure (with accompanying nausea, vomiting, cramps, dizziness, drowsiness, disorientation, or changes in urine production), lie down with your legs elevated above the level of your torso.

Missing a Dose of Perindopril + Indapamide Krka

It is essential to take the medication daily, as the effectiveness of hypertension treatment depends on regular medication intake. However, if a dose of Perindopril + Indapamide Krka is missed, take the next dose at the usual time. Do not take a double dose to make up for the missed dose.

Stopping Treatment with Perindopril + Indapamide Krka

Since hypertension treatment usually lasts a lifetime, consult your doctor before stopping treatment.
If you have any further doubts about taking this medication, consult your doctor or pharmacist.

4. Possible Side Effects

Like all medications, Perindopril + Indapamide Krka can cause side effects, although not everybody gets them.

If the Patient Experiences Any of the Following Serious Side Effects, Stop Taking the Medication and Immediately Consult a Doctor:

• severe dizziness or fainting due to low blood pressure (often - may occur in less than 1 in 10 patients);
• bronchospasm (feeling of chest tightness, wheezing, and shortness of breath; uncommon - may occur in less than 1 in 100 patients);
• facial, lip, mouth, tongue, or throat swelling, difficulty breathing - a sudden allergic reaction with shortness of breath, rash, (angioedema, see the subsection "Warnings and Precautions" in section 2); uncommon - may occur in less than 1 in 100 patients;
• severe skin reactions, including erythema multiforme (a skin rash often starting with the appearance of red, itchy spots on the face, arms, or legs) or severe skin rash, hives, redness of the skin all over the body, intense itching, blistering, peeling, and swelling of the skin, mucous membrane 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 disorders, angina pectoris, heart attack; very rare - may occur in less than 1 in 10,000 patients);
• weakness or numbness of the arms or legs, or speech disorders, which may be symptoms of a stroke (very rare - may occur in less than 1 in 10,000 patients);
• pancreatitis, which can cause severe abdominal pain radiating to the back and severe illness (very rare - may occur in less than 1 in 10,000 patients);
• jaundice (yellowing of the skin or eyes), which can be a symptom of liver inflammation (very rare - may occur in less than 1 in 10,000 patients);
• life-threatening heart rhythm disorders (frequency not known);
• liver disease causing brain dysfunction (hepatic encephalopathy; frequency not known);
• muscle weakness, cramps, tenderness, or pain, especially if the patient feels unwell or has a high fever, which may be caused by abnormal muscle breakdown (frequency not known).

The following side effects have been reported:

Common (may occur in less than 1 in 10 patients):

• skin reactions in patients prone to allergic and asthmatic reactions, headache, vision disturbances, dizziness, weakness (asthenia), tinnitus, vertigo of labyrinthine origin (feeling of spinning), tingling, shortness of breath, cough, gastrointestinal disorders (nausea, abdominal pain, loss of appetite, vomiting, abdominal discomfort, taste disturbances, dry mouth, indigestion, diarrhea, constipation), muscle cramps, allergic reactions (such as skin rashes, itching), fatigue, low potassium levels in the blood.

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

• mood changes, sleep disturbances, depression, hives, purpura (red spots on the skin), blistering, kidney function disorders, excessive sweating, impotence (inability to achieve or maintain an erection), erectile dysfunction, increased eosinophil count (a type of white blood cell), changes in laboratory test results: high potassium levels in the blood that are temporary and disappear after treatment is stopped, low sodium levels in the blood, which can cause dehydration and low blood pressure, drowsiness, fainting, palpitations (feeling of heartbeat), tachycardia (fast heart rate), hypoglycemia (very low blood sugar), vasculitis (inflammation of blood vessels), photosensitivity reactions (increased skin sensitivity to sunlight), joint pain, muscle pain, chest pain, malaise, peripheral edema, fever, increased urea levels in the blood, increased creatinine levels in the blood, falls;
• if the patient has systemic lupus erythematosus (a type of collagen disease), the symptoms of the disease may worsen),

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

• worsening of psoriasis, changes in laboratory test results: increased liver enzyme activity, high bilirubin levels in serum, increased calcium levels in blood serum, low chloride levels in the blood, low magnesium levels in the blood, decreased or absent urine production, sudden flushing 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 (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 congestion or rhinitis (inflammation of the nasal mucosa), changes in blood parameters, such as decreased white blood cell count, decreased red blood cell count, decreased hemoglobin levels, decreased hematocrit, decreased platelet count, liver function disorders.

Frequency Not Known (cannot be estimated from the available data):

• abnormal heart rhythm detected on an EKG, changes in laboratory test results: high uric acid levels and high blood sugar levels, myopia, blurred vision, visual impairment, or eye pain due to increased pressure (possible symptoms of fluid accumulation in the vascular layer surrounding the eye - excessive accumulation of fluid between the choroid and sclera - or acute glaucoma),
• cyanosis, numbness, and pain in the fingers or toes (Raynaud's phenomenon).

There may be blood, kidney, liver, or pancreas disorders, as well as changes in laboratory test results (blood tests). The doctor may recommend blood tests to monitor the patient's health.

Reporting Side Effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of this medication.

5. How to Store Perindopril + Indapamide Krka

Keep this medication out of the sight and reach of children.
Do not use this medication after the expiration date stated on the packaging. The expiration date refers to the last day of the given month.
Do not store above 25°C.
Store in the original packaging to protect from moisture.
Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Package Contents and Other Information

What Perindopril + Indapamide Krka Contains

• The active substances of the medication are perindopril tert-butylamine and indapamide. Each tablet contains 4 mg of perindopril tert-butylamine, equivalent to 3.34 mg of perindopril, and 1.25 mg of indapamide.
• Other ingredients are 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 Package

White to almost white, round, slightly convex tablets with a score line on one side. The score line on the tablet is only to facilitate breaking and not to divide into equal doses.
Packaging: 14, 20, 28, 30, 50, 56, 60, 90, or 100 tablets in blisters in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
To obtain more detailed information on the names of medicinal products in other EU member states, contact the local representative of the marketing authorization holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warsaw
Phone: 22 57 37 500
Date of Last Revision of the Leaflet:13.01.2022