Perindopril/amlodipine/indapamide Krka 7 mg/5 mg/2.5 mg tablets EFG

Patient Information Leaflet

Introduction

Patient Information Leaflet

Perindopril/Amlodipine/Indapamide Krka 7 mg/5 mg/2.5 mg tablets EFG

perindopril arginine/amlodipine/indapamide

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet Contents

1. What Perindopril/Amlodipine/Indapamide Krka is and what it is 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. How to store Perindopril/Amlodipine/Indapamide Krka
6. Contents of the pack and other information

1. What Perindopril/Amlodipine/Indapamide Krka is and what it is 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 for the treatment of high blood pressure (hypertension) in adults.

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

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

• Perindopril belongs to a group of medicines called ACE (Angiotensin-Converting Enzyme) inhibitors. It works by widening blood vessels, allowing your heart to pump blood more easily through them.
• Amlodipine is a calcium channel blocker (belonging to the group of medicines known as dihydropyridines). It works by relaxing blood vessels, allowing blood to pass through them more easily.
• Indapamide is a diuretic (belonging to the group of medicines known as sulfonamide derivatives with an indole ring). Diuretics increase the amount of urine produced by the kidneys. However, indapamide differs from other diuretics in that it produces only 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, or 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 undergoing 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 causing reduced blood flow to your kidneys (renal artery stenosis),
• if you have taken or are currently taking sacubitril/valsartan, a medicine for heart failure, as this increases the risk of angioedema (rapid swelling under the skin, for example in 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 affecting the brain and central nervous system),
• if you have low levels of potassium in your blood,
• if you have previously experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin rashes during prior treatment with ACE inhibitors, or if you or a family member has ever had such symptoms under any circumstances (a disorder called angioedema),
• if you are more than 3 months pregnant (it is also advisable to avoid perindopril/amlodipine/indapamide at the beginning of pregnancy – see Pregnancy section),
• if you have very low blood pressure (hypotension),
• if you have narrowing of the aortic valve in your heart (aortic stenosis) or cardiogenic shock (a condition where the heart cannot pump enough blood to the body),
• if you have heart failure following a heart attack,
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing 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 heart muscle disorder),

• if you have heart failure or heart rhythm disorders,

• 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 vision changes or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure, which may occur within hours to weeks after taking perindopril/amlodipine/indapamide. If untreated, this may lead to permanent vision loss. If you have previously had an allergy to penicillin or sulfonamides, you may have a higher risk of developing this,

• if you have muscle disorders, including muscle pain, tenderness, weakness, or cramps,

• if you have abnormally high levels of a hormone called aldosterone in your blood (primary aldosteronism),

• if you have a collagen vascular disease (connective tissue disorder) such as systemic lupus erythematosus or scleroderma,

• if you have diabetes,

• if you are on a low-salt diet or using salt substitutes containing potassium (a balanced level of potassium in the blood is essential),

• if you are elderly,

• if you are taking any of the following medicines for high blood pressure:

• an “angiotensin II receptor antagonist” (ARA) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes,

• aliskiren.

Your doctor may monitor your kidney function, blood pressure, and electrolyte levels (e.g. potassium) in your blood periodically. See also information under the heading “Do not take Perindopril/Amlodipine/Indapamide Krka”.

• if you are of Black African origin, as you may have a higher risk of angioedema and this medicine may be less effective in lowering your blood pressure compared to patients of non-Black origin,

• if you have gout,

• if you need to undergo a test to check your parathyroid gland function,

• if you are taking any of the following medicines, as the risk of angioedema is increased:

• racecadotril (used to treat diarrhoea),

• sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of mTor inhibitors (used to prevent organ transplant rejection and in cancer treatment),

• sacubitril (available in fixed-dose combination with valsartan), used for long-term treatment of heart failure,

• linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the class of so-called gliptins (used to treat diabetes).

Angioedema:

Angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat, causing difficulty in swallowing or breathing) has been reported in patients treated with ACE inhibitors, including perindopril. This may occur at any time during treatment. If you develop such symptoms, you must stop taking Perindopril/Amlodipine/Indapamide and seek immediate medical attention. See also section 4.

You should inform your doctor if you think you are (or may become) pregnant. Perindopril/amlodipine/indapamide is not recommended at the beginning of pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to your baby if used during this period (see sections “Pregnancy” and “Breast-feeding”).

While taking perindopril/amlodipine/indapamide, you should inform your doctor or healthcare provider if you:

• are undergoing general anaesthesia and/or major surgery,
• have recently had diarrhoea or vomiting (while being unwell),
• are to receive desensitisation treatment to reduce allergic reactions to bee or wasp stings,
• are undergoing a medical test requiring injection of an iodinated contrast agent (a substance that makes organs such as the kidney or stomach visible on X-rays).

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

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

Children and adolescents

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

Other medicines and Perindopril/Amlodipine/Indapamide Krka

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

You must avoid taking Perindopril/Amlodipine/Indapamide with:

• lithium (used to treat mania or depression),
• estramustine (used to treat cancer),
• potassium-sparing agents (e.g. triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, or 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 information under the headings “Do not take Perindopril/Amlodipine/Indapamide Krka” and “Warnings and precautions”),
• angiotensin II receptor antagonists (ARA) (used to treat high blood pressure) (e.g. valsartan, telmisartan, irbesartan…),
• dantrolene (infusion) (used to treat muscle stiffness in conditions such as multiple sclerosis or to treat malignant hyperthermia during anaesthesia, including symptoms such as high fever and muscle rigidity),
• medicines commonly used to treat diarrhoea (racecadotril) or to prevent rejection of transplanted organs (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of 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 require special monitoring:

• other medicines for high blood pressure, including diuretics (medicines that increase urine production by the kidneys), and angiotensin-converting enzyme (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 treatment of irregular heart rhythm),
• ephedrine, noradrenaline, or adrenaline (medicines used to treat low blood pressure, shock, or asthma),
• medicines used to treat mental disorders such as depression, anxiety, schizophrenia, etc. (e.g. tricyclic antidepressants, antipsychotics, imipramine-type antidepressants, neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol)),
• antibiotics used to treat bacterial infections (e.g. rifampicin, injectable erythromycin, clarithromycin, sparfloxacin, moxifloxacin),
• bepridil (used to treat angina pectoris, a condition causing chest pain),
• cisapride (used to treat reduced movement of the oesophagus and stomach),
• difemethiazene (used to treat gastrointestinal problems such as ulcers, excess acid, or hyperactive digestion),
• injectable vincamine (used to treat symptomatic 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, injectable amphotericin B),
• tetracosactide (for 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 conditions such as multiple sclerosis,
• potassium-sparing medicines used in heart failure treatment: eplerenone and spironolactone at doses between 12.5 mg and 50 mg per day; amiloride, triamterene,
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen) for pain relief, or high doses of acetylsalicylic acid, a substance present in many medicines used to relieve pain and fever, and to prevent blood clotting,
• Hypericum perforatum (St. John’s Wort, a herbal remedy 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 side effects caused by other medicines or radiotherapy used in cancer treatment),
• ritonavir, indinavir, nelfinavir (also known as protease inhibitors used to treat HIV),
• gold salts, especially when administered intravenously (used for symptomatic treatment of rheumatoid arthritis),
• iodinated contrast media (used in X-ray tests),
• calcium tablets or other calcium supplements,
• immunosuppressants (medicines that reduce the body’s defence mechanisms) used to treat autoimmune disorders or after transplantation (e.g. cyclosporine, tacrolimus),
• allopurinol (for treatment of gout),
• antiepileptic medicines such as carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone,
• trimethoprim (for treatment of infections),
• methadone (used to treat addictions).

Taking Perindopril/Amlodipine/Indapamide Krka with food and drinks

See section 3.

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

Pregnancy and breast-feeding

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

Pregnancy

Inform your doctor if you think you are (or might become) pregnant.

Your doctor will usually advise you to stop taking this medicine before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine instead of perindopril/amlodipine/indapamide. This medicine is not recommended at the beginning of pregnancy, and must not be taken after the third month of pregnancy, as it may cause serious harm to your baby if used after this time.

Breast-feeding

It has been shown that amlodipine passes into breast milk in small amounts. Inform your doctor if you are breast-feeding or planning to breast-feed. Perindopril/amlodipine/indapamide is not recommended for breastfeeding mothers, and your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is a 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 unwell, dizzy, weak, tired, or give you a headache, do not drive or operate 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; hence, it is essentially “sodium-free”.

3. How to take Perindopril/Amlodipine/Indapamide Krka

Follow exactly the instructions given by your doctor or pharmacist for taking this medicine. If in doubt, consult your doctor or pharmacist again.

The recommended dose is one tablet of Perindopril/Amlodipine/Indapamide once daily.

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 immediately or go to the nearest hospital emergency department.

The most common symptom in case of overdose is a drop in blood pressure, which may cause dizziness or fainting. If this occurs, lying down with your legs raised may help.

You may experience nausea (feeling sick), vomiting, cramps, drowsiness, confusion, and changes in the amount of urine produced by the kidneys.

You may feel lightheaded, dizzy, or weak. If your blood pressure drops severely, you may go into shock. You may feel cold and clammy, and you could lose consciousness.

Excess fluid may accumulate in the lungs (pulmonary edema), causing breathing difficulties, which may develop 24–48 hours after ingestion.

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

If you forget to take Perindopril/Amlodipine/Indapamide Krka

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

If you stop taking Perindopril/Amlodipine/Indapamide Krka

Since treatment with perindopril/amlodipine/indapamide is usually lifelong, you must speak with your doctor before stopping this medicine.

If you have any further questions about using this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Stop taking this medicine and contact your doctor immediately if you experience any of the following adverse effects, which may be serious:

• sudden wheezing, 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, causing severe breathing difficulty (angioedema) (uncommon – may affect up to 1 in 100 people),
• severe skin reactions including severe 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 mucous membranes (Stevens-Johnson syndrome) (very rare – may affect up to 1 in 10,000 people), or other allergic reactions (common – 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 (common – may affect up to 1 in 10 people),
• weakness of arms or legs, or speech problems which could be signs of a possible stroke (very rare – may affect up to 1 in 10,000 people),
• heart attack, chest pain (angina) (very rare – may affect up to 1 in 10,000 people), unusually fast or irregular heartbeat (common – may affect up to 1 in 10 people),
• inflammation of the pancreas which may cause severe abdominal and back pain accompanied by a strong feeling of illness (very rare – may affect up to 1 in 10,000 people),
• yellowing of the skin or eyes (jaundice), which could be a sign of hepatitis (very rare – may affect up to 1 in 10,000 people),
• brain disease caused by liver disease (hepatic encephalopathy) (frequency not known),
• muscle weakness, cramps, tenderness or muscle pain, especially if you also feel unwell or have a high temperature, as these may be caused by abnormal muscle breakdown (frequency not known).

In decreasing order of frequency, adverse 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 blood potassium levels, headache, numbness or tingling sensations in the limbs, drowsiness (especially at the beginning of treatment), taste disturbances, visual disturbances (including double vision), tinnitus (sensation of noises in the ears), dizziness, palpitations (awareness of heartbeat), flushing, lightheadedness, cough, difficulty breathing (dyspnea), abdominal pain, constipation, diarrhea, dyspepsia or difficulty digesting, nausea, vomiting, changes in bowel habits, pruritus, allergic reactions such as skin rashes, itching, redness of the skin, muscle cramps, ankle swelling (edema), feeling of tiredness, weakness.

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

Rhinitis (stuffy or runny nose), increase in certain white blood cells (eosinophilia), low blood sugar level (hypoglycemia), high blood potassium level which may cause abnormal heart rhythm (hyperkalemia), low blood sodium level (hyponatremia) which may lead to dehydration and low blood pressure, insomnia, mood changes, anxiety, depression, sleep disorders, loss of pain sensation, tremor, fainting, vasculitis (inflammation of blood vessels), dry mouth, hair loss, red spots on the skin (purpura), skin discoloration, increased sweating, photosensitivity reaction (skin changes) after exposure to sunlight or artificial UVA rays, formation of clusters of blisters on the skin, muscle or joint pain, back pain, urinary disorders, increased need to urinate at night, increased frequency of urination, kidney problems, impotence (inability to achieve or maintain an erection), discomfort or enlargement of breasts in men, chest pain, pain, malaise, fever, weight gain or weight loss, increased blood urea, increased blood creatinine, falls.

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

Low blood chloride level, low blood magnesium level, confusion, worsening of psoriasis, high serum bilirubin level, increased liver enzyme levels, decreased or absent urine output, acute renal failure.

Concentrated urine, feeling unwell (nausea) or sick (vomiting), muscle cramps, confusion and seizures. These symptoms may indicate a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion).

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, reduced platelet count, high blood sugar (hyperglycemia), high blood calcium level (hypercalcemia), increased muscle tone, nerve disorders which may cause weakness, eosinophilic pneumonia (a rare type of pneumonia), inflammation of the gums, abdominal swelling (gastritis), yellowing of the skin (jaundice), acute renal failure.

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

Shortness of vision (myopia), blurred vision, decreased vision or eye pain due to elevated pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma), if you have systemic lupus erythematosus (a type of collagen disease), it could worsen, abnormal electrocardiogram, tremor, postural rigidity, facial rigidity resembling a mask, slow movements and unbalanced gait with shuffling of the feet, increased uric acid, a substance that may cause or worsen gout (pain in the joint(s), especially in the feet), color change, numbness and pain in fingers or toes (Raynaud's disease).

If you experience any of these symptoms, contact your doctor as soon as possible.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es.

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

5. Storage of Perindopril/Amlodipine/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 carton and blister pack following “EXP”. The expiry date is the last day of the month indicated.

This medicine does not require any special storage temperature conditions.

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

Medicines should not be disposed of via wastewater or household waste. Return any unused medicines and their packaging to the SIGRE point at your pharmacy. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This way, you will help protect the environment.

6. Contents of the pack and other information

Composition of Perindopril/Amlodipine/Indapamide Krka

• The active substances are perindopril arginine, amlodipine, and indapamide. Each tablet contains 7 mg of perindopril arginine (equivalent to 4.75 mg of perindopril), amlodipine besilate equivalent to 5 mg of amlodipine, and 2.5 mg of indapamide.
• The other components (excipients) are calcium chloride dihydrate, microcrystalline cellulose, pregelatinized corn starch, sodium carboxymethyl starch (type A), sodium hydrogen carbonate, hydrated colloidal silica, and magnesium stearate. See section 2 “Perindopril/Amlodipine/Indapamide Krka contains sodium”.

Appearance of the product and contents of the pack

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

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

Further information on this medicinal product is available from the local representative of the Marketing Authorization Holder:

KRKA Farmacéutica, S.L.,
Calle de Anabel Segura 10,
28108 Alcobendas, Madrid,
Spain

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

Date of last review of this leaflet: January 2025

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