Package leaflet: Information for the patient

Amlessa, 4 mg + 5 mg, tablets
Amlessa, 4 mg + 10 mg, tablets
Amlessa, 8 mg + 5 mg, tablets
Amlessa, 8 mg + 10 mg, tablets
tert-butylamine perindopril + amlodipine
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

What Amlessa is and what it is used for
Important information before taking Amlessa
How to take Amlessa
Possible side effects
How to store Amlessa
Contents of the pack and other information

1. What Amlessa is and what it is used for

Amlessa is used to treat high blood pressure (hypertension) and/or stable coronary artery disease (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 Amlessa containing both active substances.
Amlessa is a combination of two active substances: perindopril and amlodipine. Perindopril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors. Amlodipine is a calcium antagonist (belonging to a group of medicines called dihydropyridines). Both active substances work by relaxing and widening blood vessels, thereby lowering blood pressure. This allows blood to flow more easily through the body and reduces the workload on the heart.

2. Important information before using Amlessa

When not to use Amlessa:

if the patient is allergic to perindopril tert-butylamine, any other ACE inhibitor, amlodipine besylate, any other dihydropyridine, or any of the other ingredients of this medicine (listed in section 6);
after the 3rd month of pregnancy (Amlessa should also be avoided during early pregnancy – see section "Pregnancy and breastfeeding");
if the patient previously experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin rash while taking ACE inhibitors, 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 where the heart cannot supply 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 enough blood, leading to breathlessness or peripheral edema 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, Amlessa may not be suitable for the patient;
if the patient has kidney disorders causing reduced blood flow 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, because this increases the risk of angioedema (rapid swelling of tissues beneath the skin, such as in the throat).

Warnings and precautions
Before starting Amlessa, 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);
the patient has other heart diseases;
the patient has liver function disorders;
the patient has kidney disease or is undergoing dialysis;
the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
the patient has collagenosis (connective tissue disease), such as systemic lupus erythematosus or scleroderma;
the patient has diabetes;
the patient is on a low-salt diet or uses salt substitutes containing potassium (potassium levels in blood need to be balanced);
the patient is elderly and dose adjustment may be necessary;
the patient is taking any of the following medicines used to treat high blood pressure:
- angiotensin II receptor antagonists (ARBs) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), especially if the patient has kidney problems related to diabetes,
- aliskiren.
the patient is taking any of the following medicines, which may increase the risk of angioedema:
- racecadotril, a medicine used to treat diarrhea,
- 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.
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.

Your doctor 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 Amlessa:".
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 Amlessa 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. Amlessa 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 Amlessa if:

general anesthesia and/or surgery are planned,
you have recently experienced diarrhea or vomiting,
LDL apheresis (removal of cholesterol from blood using a special device) is planned,
you are undergoing desensitization treatment to reduce allergic reactions to bee or wasp venom.

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

lithium (used to treat mania or depression),
estramustine (used to treat tumors),
potassium supplements (including salt substitutes), potassium-sparing diuretics (spironolactone, triamterene), and other medicines that increase blood potassium levels (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 treatment: eplerenone and spironolactone at doses from 12.5 mg to 50 mg per day.

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

other blood pressure-lowering medicines, including angiotensin II receptor antagonists (AIIRAs), aliskiren (see also sections "When not to use Amlessa" 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 Amlessa" and "Warnings and precautions".
non-steroidal anti-inflammatory drugs (e.g. ibuprofen), taken for pain relief, or high doses of acetylsalicylic acid,
antidiabetic medicines (e.g. insulin or vildagliptin),
medicines used to treat mental 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 anesthesia (symptoms include very high fever and muscle rigidity),
certain antibiotics, e.g. rifampicin, erythromycin,
clarithromycin (used for bacterial infections),
antiepileptic medicines, e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone,
itraconazole, ketoconazole (used to treat fungal infections),
alpha-adrenergic blockers 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 in cancer treatment),
corticosteroids (used to treat various disorders, including severe asthma and rheumatoid arthritis),
gold salts, especially when administered intravenously (used to treat symptoms of rheumatoid arthritis),
simvastatin (used to lower cholesterol),
ritonavir, indinavir, nelfinavir (protease inhibitors used in HIV treatment),
St John's wort (Hypericum perforatum),
verapamil, diltiazem (used for heart conditions),
medicines most commonly used to treat diarrhea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, or other mTOR inhibitors). See section "Warnings and precautions".

Amlessa may lower blood pressure more significantly if the patient is taking other antihypertensive medicines.
Amlessa with food and drink
Amlessa should be taken before a meal.
Patients taking Amlessa should not consume grapefruit juice or grapefruits, as they may increase blood levels of the active substance amlodipine, potentially leading to an unexpected intensification of Amlessa's blood pressure-lowering effect.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, 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 Amlessa before planned pregnancy or immediately after pregnancy is confirmed, and will recommend an alternative medicine. Amlessa 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 plan to breastfeed. Amlessa is not recommended during breastfeeding. Your doctor may choose another medicine if you intend to breastfeed, especially if breastfeeding a newborn or premature infant.
It has been shown that small amounts of amlodipine pass into human milk.
Driving and using machines
Amlessa 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 Amlessa affects you individually.
Amlessa contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".

3. How to use Amlessa

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 every day at the same time, in the morning before a meal. Your doctor will determine the appropriate dose for you. Usually, the dose is one tablet per day.
Amlessa is generally recommended for patients who are already taking perindopril and amlodipine as separate tablets.

Use in children and adolescents
Amlessa is not recommended for use in children and adolescents.

Taking more Amlessa than prescribed
If you have taken 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.

If you forget to take Amlessa
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 your usual time.
Do not take a double dose to make up for a missed dose.

Stopping Amlessa
Since treatment with Amlessa usually lasts for life, you should consult your doctor before stopping the medicine.

If you have any further doubts about using this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, 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, urticaria, redness of the entire body, 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 effects have been reported. If any of these adverse effects are troublesome to the patient or persist for more than a week, contact your doctor.

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

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

Uncommon adverse effects (may affect up to 1 in 100 people): mood swings, anxiety, depression, insomnia, sleep disturbances, tremor, insensitivity to pain, heart rhythm disorders, nasal mucosal inflammation (nasal congestion or runny nose), hair loss, red spots on the skin, skin discoloration, back pain, joint pain, muscle pain, chest pain, urinary disorders, nocturnal urge to urinate, 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), formation of blister clusters 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 (rapid heartbeat), vasculitis (inflammation of blood vessels), photosensitivity reactions (increased skin sensitivity to sunlight), fever, falls, changes in laboratory test results: high blood potassium levels, transient after discontinuation of treatment, low sodium levels, hypoglycaemia (very low blood sugar levels) in diabetic patients, increased blood urea levels, increased blood creatinine levels.
Rare adverse effects (may affect up to 1 in 1,000 people): 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), decreased or absence of urine output, acute kidney failure.
Very rare adverse effects (may affect up to 1 in 10,000 people): 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 body, intense itching, blister formation, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome), erythema multiforme (skin rash, often starting with red, itchy spots on the face, arms or legs), photosensitivity, changes in blood parameters such as decreased white and red blood cell counts, decreased haemoglobin concentration, decreased platelet count, blood disorders, pancreatitis which may cause severe upper abdominal pain radiating to the back and general malaise, liver function disorders, hepatitis, yellowing of the skin (jaundice), increased liver enzyme activity which may affect certain test results, abdominal distension (dyspepsia), nerve disorders which may cause weakness, tingling or numbness, increased muscle tone, swelling and/or bleeding of the gums, increased blood sugar levels (hyperglycaemia).
Frequency not known (cannot be estimated from available data): tremor, muscle rigidity, facial masking, bradykinesia and dragging gait, unsteady gait, cyanosis, numbness and pain in the fingers or toes (Raynaud's phenomenon).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects 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
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Amlessa

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the abbreviation "EXP". The expiry date refers to the last day of the specified month.
The batch number is indicated on the packaging after the abbreviation "Lot".
Store in the original packaging to protect from light and moisture.
No special temperature storage instructions apply.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Amlessa contains

The active substances are perindopril with tert-butylamine and amlodipine.
Amlessa 4 mg + 5 mg tablets: Each tablet contains 4 mg of perindopril with tert-butylamine (equivalent to 3.34 mg of perindopril) and 5 mg of amlodipine (as besylate).
Amlessa 4 mg + 10 mg tablets: Each tablet contains 4 mg of perindopril with tert-butylamine (equivalent to 3.34 mg of perindopril) and 10 mg of amlodipine (as besylate).
Amlessa 8 mg + 5 mg tablets: Each tablet contains 8 mg of perindopril with tert-butylamine (equivalent to 6.68 mg of perindopril) and 5 mg of amlodipine (as besylate).
Amlessa 8 mg + 10 mg tablets: Each tablet contains 8 mg of perindopril with tert-butylamine (equivalent to 6.68 mg of perindopril) and 10 mg of amlodipine (as besylate).
Other ingredients are: sodium hydrogen carbonate, microcrystalline cellulose, pregelatinized maize starch, sodium carboxymethyl starch (Type A), colloidal anhydrous silica, and magnesium stearate (E470b). See section 2 "Amlessa contains sodium".

What Amlessa looks like and contents of the pack
Amlessa 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. Diameter: approximately 7 mm.
Amlessa 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 is intended only to facilitate tablet fragmentation for easier swallowing and does not ensure division into equal doses.
Amlessa 8 mg + 5 mg tablets: white to almost white, round, biconvex tablets with bevelled edges, embossed with the code "U 3" on one side. Diameter: approximately 9 mm.
Amlessa 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. This 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

Manufacturers
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany
Lek Pharmaceuticals, d.d., Verovškova 57, 1526 Ljubljana, Slovenia

For further information about trade names of the medicinal product in other European Economic Area countries, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Tel. 22 57 37 500