Noliprel

Package leaflet: Information for the patient

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Noliprel, 2.5 mg + 0.625 mg, coated tablets
Perindoprilum argininum + Indapamidum
Please read all of 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 adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

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

1. What Noliprel is and what it is used for

Noliprel is a combination medicine containing two active substances: perindopril and indapamide.
It is an antihypertensive medicine used to treat high blood pressure (hypertension) in adults.
Perindopril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors.
These medicines work by relaxing blood vessels, which helps the heart pump blood more easily.
Indapamide is a diuretic medicine. Diuretics increase the amount of urine produced by the kidneys.
Indapamide differs from other diuretics in that it only slightly increases urine output.
Both active substances lower blood pressure and work together to help normalize the patient's blood pressure.

2. Important information before using Noliprel

When not to use Noliprel:

• if the patient is allergic to perindopril or other ACE inhibitors, to indapamide or other sulfonamides, or to any of the other ingredients of this medicine (listed in section 6);
• if during previous use of an ACE inhibitor the patient experienced symptoms such as wheezing, facial or tongue swelling, intense itching or severe skin rashes, or if such symptoms occurred in the patient or a relative under any circumstances (a condition called angioedema);
• if the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren;
• if the patient has severe liver disease or a condition called hepatic encephalopathy (liver disease damaging the brain);
• if the patient has severe kidney disease causing reduced blood supply to the kidneys (renal artery stenosis);
• if the patient is undergoing dialysis or blood filtration by another method. Depending on the device used, Noliprel may not be suitable for the patient;
• if the patient has low potassium levels in the blood;
• if the patient has untreated decompensated heart failure (severe fluid retention, breathing difficulties);
• if the patient is more than 3 months pregnant (it is also better to avoid using Noliprel in early pregnancy – see "Pregnancy and breastfeeding");
• if the patient has taken or is currently taking a combination medicine containing sacubitril and valsartan, used to treat heart failure, because the risk of angioedema (rapid swelling of tissues under the skin in the throat area) increases (see "Warnings and precautions" and "Noliprel with other medicines").

Warnings and precautions
Before starting Noliprel, discuss with your doctor or pharmacist if:

• the patient has aortic valve stenosis (narrowing of the main blood vessel carrying blood from the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery sten (narrowing of the blood vessel supplying blood to the kidney);
• the patient has heart failure or any other heart disease;
• the patient has kidney disease or is undergoing dialysis;
• the patient experiences worsening vision or eye pain. These may be symptoms of fluid accumulation in the choroid layer of the eye (choroidal effusion) or increased eye pressure, which may occur within hours or weeks of taking Noliprel. Untreated, these symptoms may lead to permanent vision loss. If the patient previously had an allergy to penicillin or sulfonamides, the risk of these disorders is higher;
• the patient has muscle disorders, including pain, tenderness, weakness, or cramps;
• the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• the patient has liver disease;
• the patient has a collagen disease (skin disease), such as systemic lupus erythematosus or scleroderma;
• the patient has atherosclerosis (hardening of the arteries);
• the patient has hyperparathyroidism (a disorder of parathyroid gland function);
• the patient has gout;
• the patient has diabetes;
• the patient is on a low-salt diet or uses salt substitutes containing potassium;
• the patient is taking lithium or potassium-sparing medicines (spironolactone, triamterene), or potassium supplements – these medicines should be avoided while taking Noliprel (see "Noliprel with other medicines");
• the patient is elderly;
• the patient has previously had allergic reactions to light;
• the patient experiences a severe allergic reaction with swelling of the face, lips, mouth, tongue, or throat, causing difficulty in swallowing or breathing (angioedema) – swelling may occur at any time during treatment. If such symptoms occur, treatment must be stopped and medical advice sought immediately;
• the patient is taking any of the following medicines used to treat high blood pressure:
  • an angiotensin II receptor antagonist (AIIRA), also known as a sartan – e.g. valsartan, telmisartan, irbesartan, especially if the patient has kidney problems related to diabetes;
  • aliskiren. The 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 Noliprel".
• 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 than in patients of other races;
• the patient is undergoing dialysis with high-flux membranes;
• the patient is taking any of the following medicines, which increase the risk of angioedema:
  • racecadotril (used to treat diarrhoea);
  • sirolimus, everolimus, temsirolimus, and other medicines belonging to the group of drugs called mTOR inhibitors (used to prevent rejection of transplanted organs 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 the group of drugs called gliptins (used to treat diabetes).

Angioedema
In patients treated with ACE inhibitors, including Noliprel, cases of angioedema (a severe allergic reaction with swelling of the face, lips, tongue, or throat, and difficulty swallowing or breathing) have been reported. This reaction may occur at any time during treatment. If such symptoms occur, the patient must stop taking Noliprel and contact a doctor immediately. See also section 4.
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning pregnancy. Use of Noliprel is not recommended during early pregnancy and must not be taken after the 3rd month of pregnancy, as it may cause serious harm to the unborn child (see "Pregnancy and breastfeeding").

While taking Noliprel, inform your doctor or medical staff:

• if the patient is to undergo anaesthesia and/or surgery;
• if the patient has recently had diarrhoea or vomiting, or is dehydrated;
• if dialysis or LDL apheresis (removal of cholesterol from the blood using a special device) is planned;
• if desensitisation treatment to reduce allergic reactions to bee or wasp stings is planned;
• if an imaging test requiring iodine-containing contrast agents (substances allowing organs such as the kidney or stomach to be seen in X-ray examinations) is planned;
• if vision disturbances or pain in one or both eyes occur during treatment with Noliprel. These may be symptoms of glaucoma or increased pressure in one or both eyes. The use of Noliprel should be stopped and medical advice sought.

Athletes should be aware that Noliprel contains an active substance (indapamide) which may lead to a positive result in anti-doping tests.

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

Noliprel with other medicines
Inform your doctor or pharmacist about all medicines currently taken, recently taken, or planned to be taken.

Avoid using Noliprel with:

• lithium (used to treat mania or depression);
• aliskiren (a medicine used to treat high blood pressure) in patients who do not have diabetes or kidney problems;
• potassium-sparing diuretics (e.g. triamterene, amiloride), potassium salts, or other medicines that may increase potassium levels in the body (such as heparin, a medicine used to thin the blood to prevent blood clots; trimethoprim and co-trimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole, used to treat bacterial infections);
• estramustine (used to treat cancer);
• other medicines used to treat high blood pressure: angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists.

The use of other medicines may affect treatment with Noliprel. Your doctor may recommend a dose adjustment and/or additional precautions. Inform your doctor if you are taking any of the following medicines, as special caution may be necessary:

• other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (AIIRAs) or aliskiren (see also sections "When not to use Noliprel" and "Warnings and precautions"), or diuretics (medicines that increase urine output by the kidneys);
• potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses from 12.5 mg to 50 mg per day;
• medicines most commonly used to treat diarrhoea (racecadotril) or to prevent rejection of transplanted organs (sirolimus, everolimus, temsirolimus, and other medicines belonging to the group of drugs called mTOR inhibitors). See section "Warnings and precautions".
• a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to use Noliprel" and "Warnings and precautions".
• anaesthetics;
• iodine-containing contrast agents;
• antibiotics used to treat bacterial infections (e.g. moxifloxacin, sparfloxacin, erythromycin administered by injection);
• methadone (used to treat addiction);
• procainamide (used to treat heart rhythm disorders);
• allopurinol (used to treat gout);
• antihistamines used to treat allergic reactions, such as hay fever (e.g. mizolastine, terfenadine, astemizole);
• corticosteroids used to treat various diseases, including severe asthma and rheumatoid arthritis;
• immunosuppressive medicines used to treat autoimmune diseases or to prevent organ rejection after transplantation (e.g. cyclosporine, tacrolimus);
• halofantrine (used to treat certain types of malaria);
• pentamidine (used to treat pneumonia);
• gold salts administered by injection (used to treat rheumatoid arthritis);
• vinpocetine (used to treat cognitive symptoms in elderly patients, including memory loss);
• bepridil (used to treat angina pectoris);
• medicines used for heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis preparations, bretylium);
• cisapride, difenoxin (used to treat gastrointestinal disorders);
• digoxin or other cardiac glycosides (used in heart diseases);
• baclofen (used to treat muscle stiffness occurring in diseases such as multiple sclerosis);
• medicines used to treat diabetes, such as insulin, metformin, or gliptins;
• calcium, including calcium supplements;
• stimulant laxatives (e.g. senna);
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or high doses of salicylates (e.g. acetylsalicylic acid (a substance contained in many medicines used for pain relief, fever reduction, and prevention of blood clots));
• intravenous amphotericin B (used to treat severe fungal infections);
• medicines used to treat mental disorders, such as depression, anxiety, schizophrenia (e.g. tricyclic antidepressants, neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol));
• tetracosactide (used to treat Crohn's disease);
• trimethoprim (used to treat infections);
• vasodilators, including nitrates;
• medicines used to treat low blood pressure, shock, or asthma (e.g. ephedrine, noradrenaline, or adrenaline).

Noliprel with food and drink
It is recommended to take Noliprel before a meal.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.

Pregnancy
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning pregnancy. Usually, your doctor will advise stopping Noliprel before becoming pregnant or as soon as pregnancy is confirmed, and will recommend an alternative medicine. Use of Noliprel is not recommended during early pregnancy and must not be taken after the 3rd month of pregnancy, as it may cause serious harm to the unborn child.

Breastfeeding
Use of Noliprel is not recommended if the patient is breastfeeding.
Inform your doctor immediately if you are breastfeeding or plan to breastfeed. Seek medical advice without delay.

Driving and using machines
Noliprel usually does not affect the ability to drive or operate machinery. However, some patients may experience dizziness or fatigue related to low blood pressure.
In such cases, the ability to drive or operate machinery may be impaired.

Noliprel contains lactose monohydrate
If the patient has been diagnosed with an intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

Noliprel contains sodium
Noliprel contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to use Noliprel

This medicine should always be taken as directed by your doctor or pharmacist.
If in doubt, consult your doctor or pharmacist.
The recommended dose is one tablet once daily. Your doctor may decide to increase the dose to
2 tablets per day or modify the dosing regimen if there is impaired kidney function.
The tablet should preferably be taken in the morning, before a meal. Swallow the tablet with a glass of water.
The break line on the tablet is not intended for splitting the tablet.

Taking more Noliprel than prescribed
If you have taken too many tablets, contact your doctor immediately or go to the nearest hospital emergency department.
The most commonly occurring symptom of overdose is low blood pressure.
If significantly low blood pressure occurs (accompanied by nausea, vomiting, cramps, dizziness, drowsiness, disorientation, or changes in urine output), lying down with legs elevated may help.

Missed dose of Noliprel
It is important to take the medicine every day, as regular use is most effective.
However, if you miss a dose of Noliprel, take the next dose at the usual time.
Do not take a double dose to make up for a missed dose.

Stopping Noliprel treatment
Treatment of high blood pressure is long-term; therefore, do not stop taking this medicine without consulting your doctor.
If you have any further doubts regarding the use of 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 the patient experiences any of the following adverse effects, which may be
severe, treatment with this medicine should be discontinued and medical advice should be sought immediately:

• severe dizziness or fainting due to low blood pressure (common – may occur in less than 1 in 10 patients);
• bronchospasm (feeling of tightness in the chest, wheezing and shortness of breath; uncommon – may occur in less than 1 in 100 patients);
• swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema, see section "Warnings and precautions" in point 2); uncommon
• may occur in less than 1 in 100 patients;
• severe skin reactions, including erythema multiforme (skin rash often starting with red, itchy spots on the face, arms or legs) or severe skin rash, urticaria, redness of the entire skin surface, intense itching, blistering, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome) or other allergic reactions (very rare – may occur in less than 1 in 10,000 patients);
• cardiovascular disorders (heart rhythm disturbances, angina pectoris (chest pain radiating to the jaw and back, caused by physical exertion), myocardial infarction; very rare – may occur in less than 1 in 10,000 patients);
• weakness of the arms or legs, or speech disturbances, which may be signs of stroke (very rare – may occur in less than 1 in 10,000 patients);
• pancreatitis, which may cause severe upper abdominal pain radiating to the back and general malaise (very rare – may occur in less than 1 in 10,000 patients);
• yellowing of the skin or eyes (jaundice), which may indicate liver inflammation (very rare – may occur in less than 1 in 10,000 patients);
• life-threatening heart rhythm disturbances (frequency unknown);
• brain disease caused by liver disease (hepatic encephalopathy; frequency unknown); muscle weakness, cramps, tenderness or muscle pain, particularly when the patient also feels unwell or has a high temperature, which may be due to abnormal muscle breakdown (frequency unknown).

Adverse effects, grouped by decreasing frequency of occurrence, may include:

• common (may occur in less than 1 in 10 patients): skin reactions in patients with a tendency to allergic or asthmatic reactions, headache, central dizziness, labyrinthine dizziness, prickling and tingling sensations, visual disturbances, tinnitus (perception of ringing sounds), cough, shortness of breath, gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, indigestion or digestive problems, diarrhoea, constipation), allergic reactions (such as skin rashes, itching), muscle cramps, feeling of fatigue.
• uncommon (may occur in less than 1 in 100 patients): mood swings, sleep disturbances, urticaria, purpura (small red spots on the skin), blister clusters, kidney disorders, impotence, excessive sweating, increased eosinophil count (a type of white blood cell), changes in laboratory test results: high blood potassium levels, which resolve after discontinuation of treatment, low blood sodium levels, drowsiness, fainting, palpitations (awareness of heartbeat), tachycardia (rapid heartbeat), hypoglycaemia (very low blood sugar levels) in diabetic patients, vasculitis (inflammation of blood vessels), dryness of the oral mucosa, photosensitivity reactions (increased skin sensitivity to sunlight), joint pain, muscle pain, chest pain, malaise, peripheral oedema, fever, increased blood urea levels, increased blood creatinine levels, falls.
• rare (may occur in less than 1 in 1,000 patients): worsening of psoriasis, changes in laboratory test results: increased liver enzyme activity, high serum bilirubin levels; fatigue.
• very rare (may occur in less than 1 in 10,000 patients): disorientation, eosinophilic pneumonia (a rare type of lung inflammation), rhinitis (nasal congestion or runny nose), severe kidney disorders, blood parameter changes such as decreased white blood cell and red blood cell counts, decreased haemoglobin concentration, decreased platelet count, high blood calcium levels, liver function disorders.
• frequency not known (cannot be estimated from available data): abnormal heart function detected on ECG, changes in laboratory test results: low potassium levels, high blood uric acid levels and high blood glucose levels, myopia, blurred vision, visual disturbances, worsening of vision or eye pain due to high pressure (possible symptoms of fluid accumulation in the choroid layer of the eye (choroidal effusion) or acute angle-closure glaucoma), cyanosis, numbness and pain in fingers or toes (Raynaud's phenomenon). If the patient has systemic lupus erythematosus (a type of collagenosis), symptoms of the disease may worsen. Blood, kidney, liver or pancreas disorders may occur, as well as changes in laboratory test results (blood tests). The doctor may recommend blood tests to monitor the patient's health.

After using ACE inhibitors, concentrated urine (dark-coloured urine), nausea or vomiting, muscle cramps, disorientation and seizures may occur, which could be caused by inappropriate antidiuretic hormone secretion. If such symptoms occur, medical advice should be sought as soon as possible.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform a doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store the medicine Noliprel

Keep the 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 the container tightly closed to protect it from moisture.
Medicines must 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 the medicinal product contains Noliprel

• The active substances are: perindopril and indapamide. One coated tablet contains 2.5 mg of perindopril with arginine (equivalent to 1.6975 mg of perindopril) and 0.625 mg of indapamide.
• Other ingredients of the tablet core: lactose monohydrate, magnesium stearate, maltodextrin, colloidal anhydrous silica, sodium carboxymethyl starch (type A); ingredients of the coating: glycerol, hypromellose, polyethylene glycol 6000, magnesium stearate, titanium dioxide (E 171).

What Noliprel looks like and contents of the pack
Noliprel is a white, elongated coated tablet with an embossed line on both sides. Each coated tablet contains 2.5 mg of perindopril with arginine and 0.625 mg of indapamide.

The tablets are available in a pack containing 30 tablets.
For more detailed information, please contact the Marketing Authorisation Holder or Parallel Importer.
Marketing Authorisation Holder in Lithuania, country of export:
Les Laboratoires Servier, 50, rue Carnot, 92284 Suresnes cedex, France
Manufacturer:
ANPHARM Przedsiębiorstwo Farmaceutyczne S.A., ul. Annopol 6B, 03-236 Warszawa, Poland
Les Laboratoires Servier Industrie, 905 route de Saran, 45520 Gidy, France
Servier Ireland Industries Ltd, Gorey Road, Arklow – Co. Wicklow, Ireland
Parallel Importer:
InPharm Sp. z o.o., ul. Strumykowa 28/11, 03-138 Warszawa
Repackaged in:
InPharm Sp. z o.o. Services sp. k., ul. Chełmżyńska 249, 04-458 Warszawa
Marketing Authorisation Number in Lithuania, country of export: LT/1/07/0667/004
Parallel Import Licence Number: 178/17
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria PRETERAX-ARGININ
Belgium PRETERAX 2.5 mg/0.625 mg
Cyprus COVERSYL PLUS ARGININE 2.5 mg/0.625 mg
Estonia NOLIPREL ARGININE
Finland PRETERAX NOVUM
France PRETERAX 2.5mg/0.625mg
Germany PRETERAX N 2.5 mg/ 0.625 mg Filmtabletten
Greece PRETERAX 2.5 mg/0.625 mg
Ireland COVERSYL ARGININE PLUS 2.5mg/0.625mg
Italy PRETERAX 2.5 mg/0.625 mg
Latvia NOLIPREL ARGININE 2.5mg/0.625mg apvalkotās tabletes
Lithuania NOLIPREL 2.5 mg/0.625 mg tabletès
Luxembourg PRETERAX 2.5 mg/0.625 mg
Malta PRETERAX ARGININE 2.5mg/0.625mg
Poland NOLIPREL
Portugal PRETERAX 2.5 mg/0.625 mg
Romania NOLIPREL ARG 2.5 mg/ 0.625 mg
Slovakia NOLIPREL A
Slovenia BIONOLIPREL 2.5mg/0.625mg filmsko obložene tablete

Translation of the symbols for days of the week appearing on the immediate packaging:
P. – Monday, A. – Tuesday, T. – Wednesday, K. – Thursday, Pn. – Friday, Š. – Saturday,
S. – Sunday.