Perindopril/amlodipine krka

Package leaflet: Information for the patient

Perindopril/Amlodipine Krka, 4 mg + 5 mg, tablets
Perindopril/Amlodipine Krka, 4 mg + 10 mg, tablets
Perindopril/Amlodipine Krka, 8 mg + 5 mg, tablets
Perindopril/Amlodipine Krka, 8 mg + 10 mg, tablets
tert-butylamini perindoprilum + amlodipinum
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm someone else even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Perindopril/Amlodipine Krka is and what it is used for
2. What you need to know before taking Perindopril/Amlodipine Krka
3. How to take Perindopril/Amlodipine Krka
4. Possible side effects
5. How to store Perindopril/Amlodipine Krka
6. Contents of the pack and other information

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

Perindopril/Amlodipine Krka is used to treat high blood pressure (hypertension)
and (or) stable angina (a condition in which blood flow to the heart is reduced or
blocked).
Patients already taking perindopril and amlodipine as separate tablets may switch to a single
tablet of Perindopril/Amlodipine Krka containing both active substances.
Perindopril/Amlodipine Krka is a combination of two active substances: perindopril and
amlodipine. Perindopril belongs to a group of medicines called angiotensin-converting enzyme inhibitors (ACE inhibitors).
Amlodipine is a calcium antagonist (it belongs to a group of medicines called dihydropyridines). Both
active substances work by widening and relaxing blood vessels, thereby lowering blood pressure. Blood can then flow more easily through the body, and the heart is less burdened.

2. Important information before using Perindopril/Amlodipine Krka

When not to use Perindopril/Amlodipine Krka

• if the patient is allergic to perindopril tert-butylamine or any other ACE inhibitor, amlodipine besylate or any other dihydropyridine, or any of the other ingredients of this medicine (listed in section 6);
• after the 3rd month of pregnancy (Perindopril/Amlodipine Krka should also be avoided during early pregnancy – see section "Pregnancy and breastfeeding");
• if the patient previously experienced the following symptoms while taking ACE inhibitors: wheezing, facial or tongue swelling, intense itching or severe skin rashes, or if such symptoms occurred in the patient or a family member under any other circumstances (a condition known as angioedema);
• in cardiogenic shock (a condition in which the heart cannot deliver sufficient blood to the body), aortic stenosis (narrowing of the main blood vessel leaving the heart), or unstable angina (chest pain that may occur at rest);
• in patients with very low blood pressure (severe hypotension);
• in patients with heart failure (the heart is unable to pump blood effectively, leading to breathlessness or peripheral oedema such as swelling of legs, ankles or feet) following acute myocardial infarction;
• if the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren;
• if the patient is undergoing dialysis or another form of blood filtration. Depending on the device used, Perindopril/Amlodipine Krka may not be suitable;
• if the patient has kidney disorders causing reduced blood supply to the kidneys (renal artery stenosis);
• if the patient has taken or is currently taking a combination medicine containing sacubitril and valsartan, used to treat certain types of chronic (long-term) heart failure in adults, as this increases the risk of angioedema (rapid swelling of tissues beneath the skin, such as in the throat).

Warnings and precautions
Before starting Perindopril/Amlodipine Krka, discuss with your doctor or
pharmacist:

• if the patient has hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidney);
• if the patient has other heart diseases;
• if the patient has liver function disorders;
• if the patient has kidney disease or is undergoing dialysis;
• the patient has abnormally increased levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• if the patient has a collagen disease (connective tissue disease), such as systemic lupus erythematosus or scleroderma;
• if the patient has diabetes;
• if the patient is on a low-salt diet or uses salt substitutes containing potassium (potassium levels in blood need to be balanced);
• if the patient is elderly and dose adjustment may be necessary;
• if the patient is taking any of the following medicines used to treat high blood pressure:
• an angiotensin II receptor antagonist (ARB) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), especially if the patient has kidney problems related to diabetes,
• aliskiren.
• if the patient is taking any of the following medicines, which may increase the risk of angioedema:
• racecadotril, a medicine used to treat diarrhoea,
• medicines used to prevent organ transplant rejection and in cancer treatment (e.g. sirolimus, everolimus, temsirolimus and other mTOR inhibitors),
• vildagliptin, a medicine used to treat diabetes.
• 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.

The treating physician may monitor kidney function, blood pressure and blood electrolyte levels (e.g.
potassium) at regular intervals.
See also information under the heading “When not to use Perindopril/Amlodipine Krka”.
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 reaction may occur at any
time during treatment. If such symptoms occur, stop taking Perindopril/Amlodipine Krka immediately and contact your doctor without delay. See also section 4.
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning pregnancy. Use of Perindopril/Amlodipine Krka is not recommended during early pregnancy and must not be taken after the 3rd
month of pregnancy, as it may seriously harm the unborn child if used during this period (see
section "Pregnancy and breastfeeding").
Inform your doctor or medical staff that you are taking Perindopril/Amlodipine Krka if:

• general anaesthesia and/or surgery is planned,
• you have recently experienced diarrhoea or vomiting,
• LDL apheresis (removal of cholesterol from blood using a special device) is planned,
• desensitisation treatment is planned to reduce allergic reactions to bee or wasp venom.

Children and adolescents
Perindopril/Amlodipine Krka is not recommended for use in children and adolescents.
Perindopril/Amlodipine Krka and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Avoid taking Perindopril/Amlodipine Krka with:

• lithium (used to treat mania or depression),
• estramustine (used to treat tumours),
• potassium supplements (including salt substitutes), potassium-sparing diuretics (spironolactone, triamterene) and other medicines that increase potassium levels in blood (e.g. trimethoprim and co-trimoxazole, used for bacterial infections; cyclosporine, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots),
• potassium-sparing medicines used in heart failure: eplerenone and spironolactone at doses from 12.5 mg to 50 mg per day.

Other medicines may affect the action of Perindopril/Amlodipine Krka. Inform your doctor if you are taking any of the following medicines, as special care may be needed:

• other medicines that lower blood pressure, including angiotensin II receptor antagonists (ARBs), aliskiren (see also sections "When not to use Perindopril/Amlodipine Krka" and "Warnings and precautions") or diuretics (which increase urine output by the kidneys),
• a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to use Perindopril/Amlodipine Krka" and "Warnings and precautions".
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen) taken to relieve pain or high doses of acetylsalicylic acid,
• antidiabetic medicines (e.g. insulin or vildagliptin),
• medicines used to treat psychiatric disorders such as depression, anxiety, schizophrenia, etc. (e.g. tricyclic antidepressants, antipsychotics, imipramine-type antidepressants, neuroleptics),
• immunosuppressive medicines (which suppress the immune system), used to treat autoimmune disorders or after organ transplantation (e.g. cyclosporine, tacrolimus),
• trimethoprim and co-trimoxazole (used to treat infections),
• allopurinol (used to treat gout),
• procainamide (used to treat heart rhythm disorders),
• vasodilators, including nitrates,
• ephedrine, noradrenaline or adrenaline (used to treat low blood pressure, shock or asthma),
• baclofen or dantrolene (by infusion), used to treat muscle stiffness in conditions such as multiple sclerosis; dantrolene is also used to treat malignant hyperthermia occurring during anaesthesia (symptoms include very high fever and muscle rigidity),
• certain antibiotics, e.g. rifampicin, erythromycin,
• clarithromycin (used to treat bacterial infections),
• antiepileptic medicines, e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone,
• itraconazole, ketoconazole (used to treat fungal infections),
• alpha-adrenolytic medicines, used to treat enlarged prostate, e.g. prazosin, alfuzosin, doxazosin, tamsulosin, terazosin,
• amifostine (given to prevent or reduce side effects caused by other medicines or radiotherapy, used in cancer treatment),
• corticosteroids (used to treat various disorders, including severe asthma and rheumatoid arthritis),
• gold salts, particularly when administered intravenously (used to treat symptoms of rheumatoid arthritis),
• simvastatin (used to lower cholesterol levels),
• ritonavir, indinavir, nelfinavir (protease inhibitors used in HIV treatment),
• St John's wort (Hypericum perforatum),
• verapamil, diltiazem (used in heart diseases),
• medicines most commonly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus or other mTOR inhibitors). See section "Warnings and precautions".

Perindopril/Amlodipine Krka may lower blood pressure more significantly if the patient is
taking other antihypertensive medicines.
Perindopril/Amlodipine Krka with food and drink
Perindopril/Amlodipine Krka should be taken before a meal.
Patients taking Perindopril/Amlodipine Krka should not consume grapefruit juice or grapefruits, as they may increase the blood concentration of the active substance – amlodipine – which could result in an unpredictable intensification of the blood pressure-lowering effect of Perindopril/Amlodipine Krka.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a
child, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
Inform your doctor if you are pregnant, suspect pregnancy or are planning pregnancy. Your doctor will usually advise stopping Perindopril/Amlodipine Krka before planned pregnancy or immediately after pregnancy is confirmed, and will recommend another medicine. Use of Perindopril/Amlodipine 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 if used during this period.
Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. Use of Perindopril/Amlodipine Krka is not recommended during breastfeeding. Your doctor may choose another medicine if you intend to breastfeed, particularly if breastfeeding a newborn or premature infant. Small amounts of amlodipine have been shown to pass into human milk.
Driving and operating machinery
Perindopril/Amlodipine Krka does not affect concentration, but dizziness or weakness due to low blood pressure may occur, which could impair the ability to drive or operate machinery. Do not drive or operate machinery until you know how Perindopril/Amlodipine Krka affects you individually.
Perindopril/Amlodipine Krka contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Perindopril/Amlodipine Krka

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your
doctor or pharmacist.
The tablet should be swallowed with a glass of water, preferably at the same time every day, in the morning before
a meal. Your doctor will determine the dose appropriate for you. Usually, the dose is one tablet per day.
Perindopril/Amlodipine Krka is generally recommended for patients who are already taking perindopril and
amlodipine in separate tablets.
Use in children and adolescents
Use in children and adolescents is not recommended.
Taking more Perindopril/Amlodipine 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, which may cause dizziness or
fainting.
If such symptoms occur, lie down and raise your legs.
Breathlessness caused by excess fluid accumulating in the lungs (pulmonary edema) may occur up to
24–48 hours after taking the medicine.
Missing a dose of Perindopril/Amlodipine Krka
It is important to take the medicine every day, as regular treatment is most effective. If you miss a dose,
take the next dose at the usual time.
Do not take a double dose to make up for a missed dose.
Stopping Perindopril/Amlodipine Krka
Since treatment with Perindopril/Amlodipine Krka usually lasts for life, you should consult your doctor before
stopping the medicine.
If you have any further doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following symptoms occur, stop taking the medicine immediately and
contact your doctor:

• sudden wheezing, chest pain, shortness of breath or difficulty breathing;
• swelling of the eyelids, face or lips;
• swelling of the tongue and throat, causing significant breathing difficulties;
• severe skin reactions, including severe rash, hives, 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;
• severe dizziness or fainting;
• heart attack, abnormally fast or irregular heartbeat, or chest pain;
• pancreatitis, which may cause severe upper abdominal pain radiating to the back and general malaise.

The following common adverse reactions have been reported. If any of these adverse reactions
are bothersome to the patient or persist for more than one week, contact your doctor.

• Very common adverse reactions (may affect more than 1 in 10 patients): swelling (fluid retention).
• Common adverse reactions (may affect up to 1 in 10 patients): headache, central dizziness, drowsiness (especially at the beginning of treatment), labyrinthine vertigo, tingling or numbness in the limbs, visual disturbances (including double vision), tinnitus (sensation of hearing sounds), palpitations (awareness of heartbeat), sudden facial flushing, sensation of "emptiness" in the head due to low blood pressure, cough, shortness of breath, nausea, vomiting, abdominal pain, taste disturbances, dyspepsia or digestive disturbances, changes in bowel habits, diarrhoea, constipation, allergic reactions (such as skin rashes, itching), muscle cramps, fatigue, weakness, swelling around the ankles (peripheral oedema).

Other reported adverse reactions are listed below. If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur, inform your doctor or pharmacist.

• Uncommon adverse reactions (may affect up to 1 in 100 patients): mood swings, anxiety, depression, insomnia, sleep disturbances, tremor, fainting, pain insensitivity, cardiac arrhythmias, nasal mucosal inflammation (nasal congestion or rhinitis), hair loss, red spots on the skin, skin discoloration, back pain, joint pain, muscle pain, chest pain, urinary disorders, nocturia (urinary urgency at night), increased frequency of urination, pain, malaise, bronchospasm (feeling of tightness in the chest, wheezing and shortness of breath), dryness of the oral mucosa, angioedema (symptoms such as wheezing, swelling of the face or tongue), clustering of blisters on the skin, kidney disorders, impotence, excessive sweating, increased eosinophil count (a type of white blood cell), discomfort or enlargement of the breasts in men, weight gain or weight loss, tachycardia (fast heart rate), vasculitis (inflammation of blood vessels), photosensitivity reactions (increased skin sensitivity to sunlight), fever, falls, changes in laboratory test results: high blood potassium levels (transient and resolving after discontinuation of treatment), low blood sodium levels, hypoglycaemia (very low blood sugar levels) in diabetic patients, increased blood urea levels, increased blood creatinine levels.

• Rare adverse reactions (may affect up to 1 in 1,000 patients): confusion, exacerbation of psoriasis, changes in laboratory test results: increased liver enzyme activity, high serum bilirubin levels, dark urine, nausea or vomiting, muscle cramps, disorientation and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion), reduced or absent urine output, acute kidney failure.

• Very rare adverse reactions (may affect up to 1 in 10,000 patients): cardiovascular disorders (angina pectoris, myocardial infarction and stroke),
  eosinophilic pneumonia (a rare type of lung inflammation), swelling of the eyelids, face or lips,
  swelling of the tongue and throat causing significant breathing difficulties, severe skin reactions, including severe skin rash, urticaria, redness of the entire skin surface, intense itching, blistering, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome), erythema multiforme (skin rash, often beginning with red, itchy spots on the face, arms or legs), photosensitivity, changes in blood parameters such as decreased white blood cell and red blood cell counts, decreased haemoglobin levels, decreased platelet count, blood disorders, pancreatitis, which may cause severe upper abdominal pain radiating to the back and general malaise, liver function disorders, hepatitis, jaundice (yellowing of the skin), increased liver enzyme activity (which may affect certain laboratory test results), abdominal distension (gastric irritation), nerve disorders causing weakness, tingling or numbness, increased muscle tone, gum swelling, increased blood glucose levels (hyperglycaemia).

• Frequency not known (cannot be estimated from available data): tremor, postural rigidity, facial masking, bradykinesia and dragging gait, unsteady gait, cyanosis, numbness and pain in fingers or toes (Raynaud's phenomenon).

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, inform your doctor or pharmacist. Adverse reactions can
be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: + 48 22 49 21 301
Faks: + 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/Amlodipine Krka

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from light and moisture.
No special temperature storage instructions apply.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Perindopril/Amlodipine Krka contains

• The active substances in this medicine are perindopril tert-butylamine and amlodipine.
  Perindopril/Amlodipine Krka 4 mg + 5 mg tablets
  Each tablet contains 4 mg of perindopril tert-butylamine (equivalent to 3.34 mg of perindopril) and 5 mg of amlodipine (as besylate).
  Perindopril/Amlodipine Krka 4 mg + 10 mg tablets
  Each tablet contains 4 mg of perindopril tert-butylamine (equivalent to 3.34 mg of perindopril) and 10 mg of amlodipine (as besylate).
  Perindopril/Amlodipine Krka 8 mg + 5 mg tablets
  Each tablet contains 8 mg of perindopril tert-butylamine (equivalent to 6.68 mg of perindopril) and 5 mg of amlodipine (as besylate).
  Perindopril/Amlodipine Krka 8 mg + 10 mg tablets
  Each tablet contains 8 mg of perindopril tert-butylamine (equivalent to 6.68 mg of perindopril) and 10 mg of amlodipine (as besylate).

• The other ingredients are: sodium hydrogen carbonate, microcrystalline cellulose, maize starch, sodium carboxymethyl starch (Type A), colloidal anhydrous silica, and magnesium stearate. See section 2 “Perindopril/Amlodipine Krka contains sodium”.

What Perindopril/Amlodipine Krka looks like and contents of the pack
Perindopril/Amlodipine Krka 4 mg + 5 mg tablets: white to almost white, round, slightly biconvex tablets with bevelled edges, embossed with the code “U 1” on one side of the tablet. Diameter: approximately 7 mm.
Perindopril/Amlodipine Krka 4 mg + 10 mg tablets: white to almost white, biconvex, capsule-shaped tablets with a breakline on one side. The tablets are embossed with the code “U” on one side and “2” on the other side of the breakline. Dimensions: approximately 12.5 mm x 5.5 mm. The breakline on the tablet is intended only to facilitate breaking for easier swallowing and does not allow division into equal doses.
Perindopril/Amlodipine Krka 8 mg + 5 mg tablets: white to almost white, round, biconvex tablets with bevelled edges, embossed with the code “U 3” on one side of the tablet. Diameter: approximately 9 mm.
Perindopril/Amlodipine Krka 8 mg + 10 mg tablets: white to almost white, round, biconvex tablets with bevelled edges and a breakline on one side. The tablets are embossed with the code “U” on one side and “4” on the other side of the breakline. Diameter: approximately 9 mm. The tablet can be divided into equal doses.

Pack sizes: 10, 20, 30, 60 or 90 tablets in blister packs contained in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation 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
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For further information about the names of the medicinal product in other countries of the European Economic Area, 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