Amlessini

Package leaflet: Information for the patient

Amlessini, 2.85 mg + 2.5 mg, tablets
Amlessini, 5.7 mg + 5 mg, tablets
tert-butylamini perindoprilum + amlodipinum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Amlessini is and what it is used for
2. Important information before taking Amlessini
3. How to take Amlessini
4. Possible side effects
5. How to store Amlessini
6. Contents of the pack and other information

1. What Amlessini is and what it is used for

Amlessini is a combination medicine containing two active substances: perindopril and amlodipine. Both substances help regulate high blood pressure.
Perindopril is an ACE inhibitor (ACE stands for angiotensin converting enzyme). Amlodipine is a calcium antagonist belonging to a group of medicines called dihydropyridines. Together, these medicines work by dilating and relaxing blood vessels, making it easier for blood to flow through them and helping the heart maintain normal blood circulation.
Amlessini is used to treat high blood pressure (hypertension) in adults.

2. Important information before using Amlessini

When not to use Amlessini

• if the patient is allergic to perindopril with tert-butylamine or amlodipine, or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has severe kidney problems;
• if the patient previously experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe rashes while taking an ACE inhibitor, or if such symptoms occurred in a relative under any circumstances (a condition called angioedema);
• if the patient has narrowing of the heart's aortic valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to deliver adequate blood flow to the body);
• if the patient has very low blood pressure (hypotension);
• if the patient has heart failure following a heart attack;
• if the patient is more than 3 months pregnant (it is also preferable to avoid using Amlessini in early pregnancy – see section "Pregnancy");
• 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 having blood filtered by another method – depending on the equipment used, Amlessini may not be suitable;
• if the patient has kidney problems causing reduced blood supply to the kidneys (renal artery stenosis);
• if the patient has taken or is currently taking sacubitril with valsartan, a medicine used to treat certain types of chronic (long-term) heart failure in adults, because this increases the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) (see "Warnings and precautions" and "Amlessini with other medicines").

Warnings and precautions
Before taking Amlessini, consult your doctor or pharmacist if:

• the patient has hypertrophic cardiomyopathy (a heart muscle disease);
• the patient has heart failure;
• the patient has experienced a significant rise in blood pressure (hypertensive crisis);
• the patient has any other heart conditions;
• the patient has liver disease;
• the patient has kidney disease (including after kidney transplant);
• the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• the patient has a blood vessel collagen disease (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 (adequate blood potassium levels are important);
• the patient is elderly and a dose increase is needed;
• the patient is taking any of the following medicines for high blood pressure:
• an angiotensin II receptor antagonist (AIIRA), also known as a sartan – for example, valsartan, telmisartan, irbesartan, especially if the patient has kidney problems related to diabetes;
• aliskiren; Your doctor may recommend regular monitoring of kidney function, blood pressure, and blood electrolyte levels (e.g. potassium).
• see also the section "When not to use Amlessini";
• the patient is of Black race – in this case, there is a higher risk of angioedema, and the medicine may be less effective in lowering blood pressure compared to patients of other races;
• the patient is taking any of the following medicines, as they increase the risk of angioedema:
• racecadotril, a medicine used to treat diarrhoea;
• sirolimus, everolimus, temsirolimus, and other medicines belonging to a group called mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment);
• sacubitril (available in a combination medicine containing sacubitril and valsartan), used to treat chronic heart failure;
• linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to a group called gliptins (used to treat diabetes).

Angioedema:
Angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat, and difficulty swallowing or breathing) has been reported in patients treated with ACE inhibitors, including perindopril. This reaction may occur at any time during treatment. If such symptoms occur, stop taking Amlessini immediately and contact your doctor without delay. See also section 4.
The patient must inform the doctor if she thinks she is (or might be) pregnant. Use of Amlessini is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as the medicine may seriously harm the unborn child if used during this period (see section "Pregnancy").

When taking Amlessini, also inform your doctor or medical staff if:

• the patient is to undergo general anaesthesia and/or major surgery;
• the patient has recently experienced diarrhoea or vomiting;
• LDL apheresis (removal of cholesterol from the blood using a special device) is planned;
• desensitisation treatment is planned to reduce allergic reactions to bee or wasp stings.

Children and adolescents
Amlessini must not be used in children and adolescents.

Amlessini with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.

Avoid using Amlessini with the following medicines:

• lithium (used to treat mania or depression);
• estramustine (used to treat cancer);
• potassium-sparing medicines (e.g. triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, and other medicines that may increase potassium levels in the body (such as heparin, a medicine used to thin the blood to prevent clots, trimethoprim and co-trimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole, used to treat infections, and cyclosporine, an immunosuppressant used to prevent organ transplant rejection);
• aliskiren (used to treat high blood pressure) (see also sections "When not to use Amlessini" and "Warnings and precautions");
• angiotensin II receptor antagonists (medicines used to treat high blood pressure) (e.g. valsartan, telmisartan, irbesartan, etc.);
• dantrolene (intravenous), used to treat muscle stiffness in conditions such as multiple sclerosis or in treating malignant hyperthermia that may occur during anaesthesia (symptoms include very high fever and muscle rigidity);
• a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to use Amlessini" and "Warnings and precautions".

Other medicines may affect treatment with Amlessini. Inform your doctor if the patient is taking any of the following medicines, as special precautions may be needed:

• other medicines used to treat high blood pressure, including diuretics (medicines that increase urine production by the kidneys);
• medicines most commonly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the so-called mTOR inhibitors). See section "Warnings and precautions";
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen) used to relieve pain, or high doses of acetylsalicylic acid;
• medicines used to treat diabetes (such as insulin, gliptins);
• medicines used to treat mental disorders such as depression, anxiety, schizophrenia, etc. (e.g. tricyclic antidepressants, antipsychotics, imipramine-like antidepressants, neuroleptics);
• immunosuppressants (which weaken the body's immune defenses), used to treat autoimmune diseases or after organ transplantation (e.g. cyclosporine, tacrolimus);
• allopurinol (used to treat gout);
• procainamide (used to treat heart rhythm disorders);
• vasodilators, including nitrates;
• ephedrine, noradrenaline, or adrenaline (medicines used to treat low blood pressure, shock, or asthma);
• baclofen, used to treat muscle stiffness in conditions such as multiple sclerosis;
• certain antibiotics, such as rifampicin, erythromycin, clarithromycin (used for bacterial infections);
• antiepileptic medicines such as carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone;
• itraconazole, ketoconazole (medicines used to treat fungal infections);
• alpha-adrenergic receptor blockers, used to treat benign prostatic hyperplasia (e.g. prazosin, alfuzosin, doxazosin, tamsulosin, terazosin);
• amifostine (used to prevent or reduce side effects associated with other cancer medicines or radiotherapy);
• corticosteroids (used to treat various conditions, including severe asthma and rheumatoid arthritis);
• gold salts, especially when given intravenously (used to treat symptoms of rheumatoid arthritis);
• ritonavir, indinavir, nelfinavir (so-called protease inhibitors used to treat HIV);
• potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses from 12.5 mg to 50 mg per day;
• Hypericum perforatum (St. John's wort, used to treat depression).

Amlessini with food and drink
See section 3.
Patients taking Amlessini should not eat grapefruit or drink grapefruit juice, as grapefruit and grapefruit juice may increase the concentration of the active substance – amlodipine – which could lead to an unexpected increase in the blood pressure-lowering effect of Amlessini.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor or pharmacist before taking this medicine.

Pregnancy
The patient must inform her doctor if she suspects (or is planning) pregnancy. Usually, the doctor will advise stopping Amlessini before becoming pregnant or as soon as she learns she is pregnant, and will recommend an alternative medicine. Use of Amlessini is not recommended in early pregnancy and must not be taken after the third month of pregnancy, as the medicine may seriously harm the unborn child if used beyond the third month.

Breastfeeding
It has been shown that small amounts of amlodipine pass into human milk. Inform the doctor if the patient is breastfeeding or plans to breastfeed. Use of Amlessini is not recommended in breastfeeding mothers, and the doctor may choose an alternative treatment if the patient wishes to breastfeed, especially if the baby is a newborn or was born prematurely.

Driving and using machines
Amlessini may affect the ability to drive or operate machinery. If nausea, dizziness, weakness, fatigue, or headache occur, the patient should not drive or operate machinery and should contact the doctor immediately.

Amlessini 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 Amlessini

This medicine should always be used exactly as prescribed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.

The recommended dose is one tablet of Amlessini 2.85 mg + 2.5 mg once daily.

If the patient has moderate kidney function impairment, at the beginning of treatment the doctor may prescribe one tablet of Amlessini 2.85 mg + 2.5 mg every other day.

Depending on the patient's response to treatment, the doctor may decide to increase the dose after one month of treatment, if necessary, to 5.7 mg + 5 mg of Amlessini once daily.

One tablet of Amlessini 5.7 mg + 5 mg once daily is the maximum recommended dose for the treatment of high blood pressure.

The tablet should best be taken at the same time each day, in the morning, before a meal.

Do not take a higher dose than prescribed.

Taking more Amlessini than recommended
If too many tablets are taken, seek immediate medical advice from your doctor or go to the nearest hospital emergency department. The most common symptom of overdose is low blood pressure, which may cause dizziness or fainting. In such a case, lying down with legs raised may be helpful.
Breathing difficulties due to fluid accumulation in the lungs (pulmonary edema) may occur up to 24–48 hours after taking the medicine.

Missing a dose of Amlessini
It is important to take the medicine every day, as regular use is more effective. However, if a dose of Amlessini is missed, the next dose should be taken at the usual time. Do not take a double dose to make up for a missed dose.

Stopping Amlessini treatment
Treatment with Amlessini is usually long-term; therefore, consult your doctor before stopping the tablets.

If you have any further questions 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 potentially serious adverse symptoms occur in a patient, treatment with the medicine should be discontinued and medical advice should be sought immediately:

• sudden onset of wheezing, chest pain, breathlessness or difficulty breathing (bronchospasm) (uncommon – may occur in less than 1 in 100 patients);
• swelling of the eyelids, face or lips (uncommon – may occur in less than 1 in 100 patients);
• swelling of the tongue and throat, which may cause severe breathing difficulties (angioedema) (uncommon – may occur in less than 1 in 100 patients);
• severe skin reactions, including severe rash, urticaria, redness of the entire skin surface, intense itching (erythema multiforme) (very rare – may occur in less than 1 in 10,000 patients), blistering, peeling and swelling of the skin (toxic epidermal necrolysis) (very rare – may occur in less than 1 in 10,000 patients), mucosal inflammation (Stevens-Johnson syndrome, very rare – may occur in less than 1 in 10,000 patients, and toxic epidermal necrolysis, frequency cannot be estimated from available data), or other allergic reactions (uncommon – may occur in less than 1 in 100 patients);
• severe dizziness or fainting due to low blood pressure (common – may occur in less than 1 in 10 patients);
• weakness of arms or legs, or difficulty speaking, which may indicate stroke (very rare – may occur in less than 1 in 10,000 patients);
• heart attack, chest pain (angina pectoris) (very rare – may occur in less than 1 in 10,000 patients), abnormally fast or irregular heartbeat (common – may occur in less than 1 in 10 patients);
• pancreatitis, which may cause severe upper abdominal pain radiating to the back and severe malaise (very rare – may occur in less than 1 in 10,000 patients);
• yellowing of the skin or eyes (jaundice), which may be a sign of liver inflammation (very rare – may occur in less than 1 in 10,000 patients).

The following adverse reactions have been reported with the medicine Amlessini. If any of these effects are troublesome to the patient, consult a doctor:

• common adverse reactions (may occur in less than 1 in 10 patients): sensation of "emptiness" in the head, cough, swelling (fluid retention);
• uncommon adverse reactions (may occur in less than 1 in 100 patients): high potassium levels in the blood, which may cause heart rhythm disturbances (hyperkalaemia), increased blood glucose (hyperglycaemia), fatigue.

The following adverse reactions have been reported with perindopril or amlodipine, which were not observed or were observed with higher frequency with perindopril or amlodipine than with the medicine Amlessini. These adverse reactions may also occur with the use of Amlessini. If any of these effects are troublesome to the patient, consult a doctor:

• very common adverse reactions (may occur in at least 1 in 10 patients):
  swelling (fluid retention);

• common adverse reactions (may occur in less than 1 in 10 patients):
  headache, drowsiness (especially at the beginning of treatment), taste disturbance, tingling or numbness in the limbs, vertigo, visual disturbances (including double vision), tinnitus (perception of ringing or other sounds), palpitations (awareness of heart beat), sudden facial redness (hot flushes), breathlessness, abdominal pain, nausea, vomiting, indigestion or digestive disturbances, changes in bowel rhythm, constipation, diarrhoea, itching, rash, redness of the skin, pruritus, ankle swelling, muscle cramps, fatigue, weakness;

• uncommon adverse reactions (may occur in less than 1 in 100 patients):
  increased number of a certain type of white blood cells (eosinophilia), low sodium levels in the blood (hyponatraemia), low blood glucose (hypoglycaemia), mood swings, anxiety, insomnia, depression, sleep disorders, fainting, pain insensitivity, tremor, vasculitis, nasal mucosal inflammation (nasal congestion or discharge), dryness of the oral mucosa, excessive sweating, hair loss, red spots on the skin, skin discoloration, formation of clusters of blisters on the skin, photosensitivity, back pain, muscle or joint pain, urinary disorders, increased need to urinate at night, increased frequency of urination, kidney disorders, impotence, discomfort or enlargement of the breasts in men, chest pain, malaise, pain, weight gain or loss, increased blood urea, increased blood creatinine, falls, fever;

• rare adverse reactions (may occur in less than 1 in 1,000 patients):
  acute kidney failure; symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion): dark-coloured urine, nausea or vomiting, muscle cramps, confusion and seizures; reduced or absent urine output; exacerbation of psoriasis; high serum bilirubin levels; increased liver enzyme activity;

• very rare adverse reactions (may occur in less than 1 in 10,000 patients):
  blood disorders such as decreased numbers of white and red blood cells, decreased haemoglobin concentration, decreased platelet count, increased muscle tension, nerve disorders which may cause weakness, tingling or numbness, eosinophilic pneumonia (a rare type of lung inflammation), gum swelling, abdominal distension (gastritis), yellowing of the skin (jaundice);

• frequency not known (cannot be estimated from available data):
  tremor, rigidity, mask-like facial expression, bradykinesia (slowness of movement) and shuffling 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 possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist.
Adverse reactions can be reported directly to the Department of Monitoring of 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 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 Amlessini

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the stated month.
Store below 30°C.
Keep in the original packaging to protect from light and moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such practices help protect the environment.

6. Contents of the package and other information

What Amlessini contains

• The active substances are perindopril with tert-butylamine and amlodipine.
  Amlessini 2.85 mg + 2.5 mg tablets: Each tablet contains 2.85 mg of perindopril with tert-butylamine (equivalent to 2.38 mg of perindopril) and 2.5 mg of amlodipine (as amlodipine besylate).
  Amlessini 5.7 mg + 5 mg tablets: Each tablet contains 5.7 mg of perindopril with tert-butylamine (equivalent to 4.76 mg of perindopril) and 5 mg of amlodipine (as amlodipine besylate).
• Other ingredients are: sodium hydrogen carbonate, microcrystalline cellulose, pregelatinized maize starch, sodium carboxymethyl starch (type A), colloidal anhydrous silica, and magnesium stearate. See section 2 "Amlessini contains sodium".

What Amlessini looks like and contents of the pack
Amlessini 2.85 mg + 2.5 mg tablets: white or almost white, round, biconvex tablets with bevelled edges. Diameter: 5.5 mm.
Amlessini 5.7 mg + 5 mg tablets: white or almost white, round, biconvex tablets with bevelled edges and a breakline on one side. Diameter: 7 mm. The breakline on the tablet is not intended for splitting the tablet.
The tablets are available in cardboard boxes containing:

• 30, 60 or 90 tablets in blisters.

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, please contact the local representative of the Marketing Authorisation Holder:
Krka - Polska Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
telephone: +48 22 573 75 00