PERINDOPRIL/AMLODIPINE/INDAPAMIDE KRKA 7mg/5mg/2.5mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Perindopril/Amlodipine/Indapamide Krka7 mg/5 mg/2.5 mg film-coated tablets EFG

perindopril arginine/amlodipine/indapamide

Read the entire package leaflet carefully before starting to take this medicine, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed to you only, and you should 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, talk to your doctor or pharmacist, even if they are not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Perindopril/Amlodipine/Indapamide Krka and what is it used for
2. What you need to know before taking Perindopril/Amlodipine/Indapamide Krka
3. How to take Perindopril/Amlodipine/Indapamide Krka
4. Possible side effects
5. Storage of Perindopril/Amlodipine/Indapamide Krka
6. Package contents and further information

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

Perindopril/Amlodipine/Indapamide Krka is a combination of three active substances: perindopril, amlodipine, and indapamide.

Perindopril/amlodipine/indapamide is an antihypertensive medicine used to treat high blood pressure in adults.

Patients who are already taking perindopril/amlodipine as a fixed-dose combination and indapamide in separate tablets may take instead one tablet of Perindopril/Amlodipine/Indapamide Krka containing the three active substances at the same doses.

Each of the active substances lowers blood pressure, and they all work together to control your blood pressure:

• Perindopril belongs to a group of medicines called ACE inhibitors (Angiotensin-Converting Enzyme inhibitors). It works by widening the blood vessels, making it easier for your heart to pump blood through them.
• Amlodipine is a calcium channel blocker (belonging to the group of medicines called dihydropyridines). It works by relaxing the blood vessels, allowing blood to pass through them more easily.
• Indapamide is a diuretic (belonging to the group of medicines called sulfamoylindoles with an indole ring). Diuretics increase the amount of urine produced by the kidneys. However, indapamide is different from other diuretics, as it only produces a slight increase in the amount of urine formed.

2. What you need to know before taking Perindopril/Amlodipine/Indapamide Krka

Do not take Perindopril/Amlodipine/Indapamide Krka

• if you are allergic to perindopril or any other ACE inhibitor, to amlodipine or any other calcium antagonist, and to indapamide or any other sulfonamide or to any of the other ingredients of this medicine (listed in section 6),
• if you have severe kidney disease,
• if you are having dialysis or any other type of blood filtration. Depending on the machine used, perindopril/amlodipine/indapamide may not be suitable for you,
• if you have kidney problems that reduce the blood flow to your kidneys (renal artery stenosis),
• if you have taken or are currently taking sacubitril/valsartan, a medicine for heart failure, as it increases the risk of angioedema (rapid swelling under the skin in an area such as the throat) (see "Warnings and precautions" and "Other medicines and Perindopril/Amlodipine/Indapamide Krka"),
• if you have severe liver disease or suffer from a condition called hepatic encephalopathy (liver problems that affect the brain and central nervous system),
• if you have low potassium levels in your blood,
• if you have experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin rashes with previous treatment with ACE inhibitors, or if you or a member of your family has had these symptoms in any other circumstance (a condition called angioedema),
• if you are more than 3 months pregnant (it is also recommended to avoid perindopril/amlodipine/indapamide during the start of pregnancy - see section Pregnancy),
• if you have very low blood pressure (hypotension),
• if you have a narrowing of the aortic valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to pump enough blood to the body),
• if you have heart failure after a heart attack,
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine that contains aliskiren.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Perindopril/Amlodipine/Indapamide:

• if you have had photosensitivity reactions,
• if you have hypertrophic cardiomyopathy (a disease of the heart muscle),
• if you have heart failure or heart rhythm problems,
• if you have severe high blood pressure (hypertensive crises),
• if you have any other heart problems,
• if you have liver problems,
• if you have kidney problems (including kidney transplant),
• if you experience a decrease in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in your eye, and can occur within hours to weeks after taking perindopril/amlodipine/indapamide. If left untreated, this can lead to permanent vision loss. If you have previously had an allergy to penicillin or sulfonamides, you may be at greater risk of developing this,
• if you have muscle disorders, including muscle pain, sensitivity, weakness, or cramps,
• if you have abnormally high levels of a hormone called aldosterone in your blood (primary aldosteronism),
• if you have a vascular disease of the collagen (a disease of the connective tissue) such as systemic lupus erythematosus or scleroderma,
• if you have diabetes,
• if you are on a low-salt diet or are using salt substitutes that contain potassium (it is essential to have a balanced level of potassium in the blood),
• if you are an elderly patient,
• if you are taking any of the following medicines used to treat high blood pressure:

• an "angiotensin II receptor antagonist" (ARA) (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 the amount of electrolytes (such as potassium) in your blood periodically. See also the information under the heading "Do not take Perindopril/Amlodipine/Indapamide Krka".

• if you are of black African origin, as you may be at greater risk of angioedema and this medicine may be less effective in lowering your blood pressure than in patients who are not of black African origin,
• if you have gout,
• if you need to undergo a test to check that your parathyroid gland is working properly,
• if you are taking any of the following medicines, as the risk of angioedema is greater:

• racecadotril (used to treat diarrhea),
• sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of so-called mTor inhibitors (used to prevent organ rejection after transplantation and for cancer),
• sacubitril (available as a fixed-dose combination with valsartan), used to treat long-term heart failure,
• linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the class of so-called gliptins (used to treat diabetes).

Angioedema:

In patients treated with ACE inhibitors, including perindopril, angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat with difficulty swallowing or breathing) has been reported. This can occur at any time during treatment. If you develop these symptoms, you should stop taking Perindopril/Amlodipine/Indapamide and see a doctor immediately. See also section 4.

You should inform your doctor if you think you are (or might become) pregnant. Perindopril/amlodipine/indapamide is not recommended at the start of pregnancy, and should not be taken after the third month of pregnancy, as it may cause serious harm to your baby if used after the third month of pregnancy.

When taking perindopril/amlodipine/indapamide, you should inform your doctor or healthcare professional if you:

• are going to have a general anesthetic and/or major surgery,
• have recently suffered from diarrhea or vomiting (being sick),
• are going to receive desensitization treatment to reduce the effects of allergic reactions to bee or wasp stings,
• are going to undergo any medical test that requires the injection of an iodine-containing contrast agent (a substance that allows organs such as the kidney or stomach to be visible on X-rays).

Your doctor may recommend that you have blood tests to check for low sodium or potassium levels or high calcium levels.

Athletes should be aware that Perindopril/Amlodipine/Indapamide contains an active substance (indapamide) that may give a positive result in a doping test.

Children and adolescents

Perindopril/amlodipine/indapamide should not be given to children or adolescents.

Other medicines and Perindopril/Amlodipine/Indapamide Krka

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

You should avoid taking Perindopril/Amlodipine/Indapamide with:

• lithium (used to treat mania or depression),
• estr Mustine (used to treat cancer),
• potassium-sparing medicines (e.g., triamterene, amiloride), potassium supplements, or salt substitutes that contain potassium, other medicines that may increase potassium levels in your body (such as heparin, a medicine used to thin the blood and prevent clots; trimethoprim and cotrimoxazole, also known as trimethoprim/sulfamethoxazole, for bacterial infections),
• aliskiren (used to treat high blood pressure), (see also the information under the heading "Do not take Perindopril/Amlodipine/Indapamide Krka" and "Warnings and precautions"),
• angiotensin II receptor antagonists (ARAs) (used to treat high blood pressure) (e.g., valsartan, telmisartan, irbesartan...),
• dantrolene (perfusion) (used to treat muscle stiffness in diseases such as multiple sclerosis or to treat malignant hyperthermia during anesthesia, including symptoms such as high fever and muscle stiffness),
• medicines commonly used to treat diarrhea (racecadotril) or to prevent organ rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of so-called mTor inhibitors). See section "Warnings and precautions",
• sacubitril/valsartan (used to treat long-term heart failure). See sections "Do not take Perindopril/Amlodipine/Indapamide Krka" and "Warnings and precautions".

Treatment with perindopril/amlodipine/indapamide may be affected by other medicines. Make sure to inform your doctor if you are taking any of the following medicines, as you may need special care:

• other medicines for high blood pressure, including diuretics (medicines that increase the amount of urine produced by the kidneys) and ACE inhibitors (used to treat high blood pressure and heart failure),
• medicines for heart rhythm disorders (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis, bretylium),
• procainamide (for the treatment of irregular heartbeat),
• ephedrine, noradrenaline, or adrenaline (medicines used to treat low blood pressure, shock, or asthma),
• medicines used to treat mental problems such as depression, anxiety, schizophrenia, etc. (e.g., tricyclic antidepressants, antipsychotics, imipramine-type antidepressants, neuroleptics (such as amisulpride, sulpiride, sultoprida, tiaprida, haloperidol, droperidol)),
• antibiotics used to treat bacterial infections (e.g., rifampicin, erythromycin injection, clarithromycin, sparfloxacin, moxifloxacin),
• bepridil (used to treat angina pectoris, a condition that causes chest pain),
• cisapride, (used to treat reduced movement of the esophagus and stomach),
• difemanil (used to treat gastrointestinal problems such as ulcers, too much acid, hyperactive digestive system),
• vincamine injection (used to treat cognitive disorders in elderly patients, including memory loss),
• halofantrine (an antiparasitic medicine used to treat certain types of malaria),
• pentamidine (used to treat certain types of pneumonia),
• antihistamines used to treat allergic reactions, such as hay fever (e.g., mizolastine, astemizole, terfenadine),
• antifungal medicines (e.g., itraconazole, ketoconazole, amphotericin B injection),
• tetracosactide (for the treatment of Crohn's disease),
• stimulant laxatives,
• medicines for the treatment of diabetes (such as insulin, gliptins, metformin),
• baclofen used to treat muscle stiffness in diseases such as multiple sclerosis,
• potassium-sparing medicines used in the treatment of heart failure: eplerenone and spironolactone at doses between 12.5 mg and 50 mg per day; amiloride, triamterene,
• non-steroidal anti-inflammatory medicines (e.g., ibuprofen) to relieve pain or high doses of acetylsalicylic acid, a substance found in many medicines used to relieve pain and reduce fever, as well as to prevent blood clotting,
• Hypericum perforatum(St. John's Wort, a medicinal plant used to treat depression),
• vasodilators, including nitrates (medicines that dilate blood vessels),
• corticosteroids (used to treat various disorders, including severe asthma and rheumatoid arthritis),
• alpha-blockers used to treat prostate enlargement, such as prazosin, alfuzosin, doxazosin, tamsulosin, terazosin,
• amifostine (used to prevent or reduce the side effects caused by other medicines or by radiation therapy used to treat cancer),
• ritonavir, indinavir, nelfinavir (also known as protease inhibitors used to treat HIV),
• gold salts, especially when given intravenously (used to treat rheumatoid arthritis),
• iodine-containing contrast agents (used for X-ray tests),
• calcium tablets or other calcium supplements,
• immunosuppressants (medicines that reduce the body's defense mechanisms) used to treat autoimmune disorders or after transplantation (e.g., cyclosporine, tacrolimus),
• allopurinol (for the treatment of gout),
• antiepileptic medicines such as carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone,
• trimethoprim (for the treatment of infections),
• methadone (used to treat addiction).

Taking Perindopril/Amlodipine/Indapamide Krka with food and drinks

See section 3.

People taking perindopril/amlodipine/indapamide should not consume grapefruit juice or grapefruit. This is because grapefruit and grapefruit juice can lead to an increase in the levels of the active ingredient amlodipine in the blood, which can cause an unpredictable increase in the blood pressure-lowering effect of this medicine.

Pregnancy and breastfeeding

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

Pregnancy

You should inform your doctor if you think you are (or might become) pregnant.

Your doctor will normally advise you to stop taking this medicine before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of perindopril/amlodipine/indapamide. This medicine is not recommended during the first trimester of pregnancy, and should not be taken after the third month of pregnancy, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breastfeeding

Amlodipine has been shown to pass into breast milk in small amounts. Inform your doctor if you are breastfeeding or plan to breastfeed. Perindopril/amlodipine/indapamide is not recommended for breastfeeding mothers, and your doctor may choose another treatment for you if you want to breastfeed your baby, especially if your baby is newborn or premature.

Driving and using machines

Perindopril/Amlodipine/Indapamide may affect your ability to drive or use machines. If the tablets make you feel sick, dizzy, weak, or tired, or give you a headache, do not drive or use machinery and consult your doctor immediately.

Perindopril/Amlodipine/Indapamide Krka contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How to take Perindopril/Amlodipine/Indapamide Krka

Follow the administration instructions for this medication exactly as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is one Perindopril/Amlodipine/Indapamide tablet once a day.

Take the tablet preferably at the same time each day, in the morning and before breakfast.

Do not exceed the prescribed dose.

If you take more Perindopril/Amlodipine/Indapamide Krka than you should

If you take too many tablets, contact your doctor or go to the emergency department of your nearest hospital immediately.

The most frequent symptom in case of overdose is a decrease in blood pressure that can cause dizziness or fainting. If this occurs, it may help to lie down with your legs raised.

It can cause nausea (feeling of dizziness), vomiting, cramps, drowsiness, confusion, and changes in the amount of urine produced by the kidneys.

You may feel dizzy, lightheaded, or weak. If the drop in your blood pressure is severe enough, you may suffer from shock. You may feel your skin cold and wet, and you may lose consciousness.

Excess fluid may accumulate in the lungs (pulmonary edema) causing difficulty breathing, which can develop up to 24-48 hours after ingestion.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Perindopril/Amlodipine/Indapamide Krka

It is essential to take this medication every day, as continuous treatment works better. However, if you forget to take a dose of perindopril/amlodipine/indapamide, take the next dose at the usual time. Do not take a double dose to make up for the missed doses.

If you stop treatment with Perindopril/Amlodipine/Indapamide Krka

Since treatment with perindopril/amlodipine/indapamide is usually for life, you should talk to your doctor before stopping this medication.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Stop treatment with this medication and go to your doctor immediately if you experience any of the following side effects that can be serious:

• Sudden whistling when breathing, chest pain, shortness of breath, or difficulty breathing (bronchospasm) (uncommon - may affect up to 1 in 100 people),
• Swelling of the eyelids, face, or lips (uncommon - may affect up to 1 in 100 people),
• Swelling of the mouth, tongue, and throat, which causes great difficulty breathing (angioedema) (uncommon - may affect up to 1 in 100 people),
• Severe skin reactions, including intense skin rash, hives, redness of the skin all over the body, intense itching (erythema multiforme) (very rare - may affect up to 1 in 10,000 people), blistering, peeling, and inflammation of the skin (exfoliative dermatitis) (very rare - may affect up to 1 in 10,000 people), inflammation of the mucous membranes (Stevens-Johnson syndrome) (very rare - may affect up to 1 in 10,000 people), or other allergic reactions (frequent - may affect up to 1 in 10 people), toxic epidermal necrolysis (frequency not known - frequency cannot be estimated from available data),
• Severe dizziness or fainting (frequent - may affect up to 1 in 10 people),
• Weakness in arms or legs, or speech problems that could be a sign of a possible stroke (very rare - may affect up to 1 in 10,000 people),
• Heart attack, chest pain (angina) (very rare - may affect up to 1 in 10,000 people), unusually fast or abnormal heartbeat (frequent - may affect up to 1 in 10 people),
• Pancreatitis, which can cause intense abdominal and back pain accompanied by a great feeling of discomfort (very rare - may affect up to 1 in 10,000 people),
• Yellowing of the skin or eyes (jaundice) that could be a sign of hepatitis (very rare - may affect up to 1 in 10,000 people),
• Brain disease caused by liver disease (hepatic encephalopathy) (frequency not known),
• Muscle weakness, cramps, sensitivity, or muscle pain, and especially if you feel unwell or have a high temperature, as they can be caused by abnormal muscle breakdown (frequency not known).

In decreasing order of frequency, side effects may include:

Very common (may affect more than 1 in 10 people):

Edema (fluid retention).

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

Low potassium levels in the blood, headache, numbness or tingling in the extremities, drowsiness (especially at the beginning of treatment), changes in taste, changes in vision (including double vision), tinnitus (ringing in the ears), vertigo, palpitations (feeling the heartbeat), flushing, dizziness, cough, difficulty breathing (dyspnea), abdominal pain, constipation, diarrhea, dyspepsia, or difficulty digesting, nausea, vomiting, changes in bowel habits, itching, allergic reactions such as skin rashes, itching, redness of the skin, muscle cramps, swelling of the ankles (edema), feeling of fatigue, weakness.

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

Rhinitis (congested or runny nose), increased number of certain white blood cells (eosinophilia), low blood sugar levels (hypoglycemia), high potassium levels in the blood that can cause an abnormal heartbeat (hyperkalemia), low sodium levels in the blood (hyponatremia) that can cause dehydration and low blood pressure, insomnia, mood changes, anxiety, depression, sleep disorders, loss of pain sensation, tremors, fainting, vasculitis (inflammation of blood vessels), dry mouth, hair loss, red spots on the skin (purpura), skin discoloration, increased sweating, photosensitivity reaction (changes in skin appearance) after exposure to sun or artificial UVA rays, formation of blisters on the skin, muscle or joint pain, back pain, urination disorders, increased need to urinate at night, increased frequency of urination, kidney problems, impotence (inability to have or maintain an erection), discomfort or enlargement of the breasts in men, chest pain, pain, feeling of discomfort, fever, increased urea in the blood, increased creatinine in the blood, fall.

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

Low chloride levels in the blood, low magnesium levels in the blood, confusion, worsening of psoriasis, high bilirubin levels in the blood, increased liver enzyme levels, decreased or absent diuresis, acute kidney failure.

Concentrated urine, feeling of discomfort (nausea) or being sick (vomiting), muscle cramps, confusion, and convulsions. These symptoms can be from a disease called SIADH (inadequate secretion of antidiuretic hormone).

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

Changes in blood parameters such as decreased number of white and red blood cells, decreased hemoglobin concentration, decreased platelet count, high blood sugar levels (hyperglycemia), high calcium levels in the blood (hypercalcemia), increased muscle tension, nerve disorder that can cause weakness, eosinophilic pneumonia (a rare type of pneumonia), gum inflammation, abdominal swelling (gastritis), yellowing of the skin (jaundice), acute kidney failure.

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

Short-sightedness (myopia), blurred vision, 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 type of collagen disease) it could worsen, abnormal electrocardiogram, tremors, postural rigidity, facial rigidity similar to a mask, slow movements, and imbalance in gait with foot dragging, increased uric acid, a substance that can cause or worsen gout (pain in the joints, especially in the feet), color change, numbness, and pain in the fingers of the hands or feet (Raynaud's disease).

If you have these symptoms, contact your doctor as soon as possible.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System for Human Use: www.notificaram.es.

By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Perindopril/Amlodipine/Indapamide Krka

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the box and blister pack after "EXP". The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature.

Keep it in the original packaging to protect it from light and moisture.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE collection point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Perindopril/Amlodipine/Indapamide Krka

• The active ingredients are perindopril arginine, amlodipine, and indapamide. Each tablet contains 7 mg of perindopril arginine (equivalent to 4.75 mg of perindopril), amlodipine besylate equivalent to 5 mg of amlodipine, and 2.5 mg of indapamide.
• The other ingredients (excipients) are calcium chloride hexahydrate, microcrystalline cellulose, pregelatinized cornstarch, sodium carboxymethylcellulose (type A), sodium hydrogen carbonate, colloidal silica, and magnesium stearate. See section 2 "Perindopril/Amlodipine/Indapamide Krka contains sodium".

Appearance of the product and package contents

The Perindopril/Amlodipine/Indapamide Krka tablets are white or almost white, round (8 mm in diameter), biconvex, marked with K4 on one side.

The Perindopril/Amlodipine/Indapamide Krka tablets are available in packs of 10, 30, 60, 90, 100, or 120 tablets, in a box.

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

KRKA, d.d., Novo mesto,

Šmarješka cesta 6,

8501 Novo mesto,

Slovenia

Manufacturer

KRKA, d.d., Novo mesto,

Šmarješka cesta 6,

8501 Novo mesto,

Slovenia

Or

TAD PHARMA GMBH

Heinz Lohmann strasse, 5

D-27472 Groden Cuxhaven

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

KRKA Farmacéutica, S.L.,

Calle de Anabel Segura 10,

28108 Alcobendas, Madrid,

Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Date of the last revision of this leaflet: January 2025

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).