Noliprel bi-forte

Package leaflet: Information for the patient

Noliprel Bi-Forte, 10 mg + 2.5 mg, film-coated tablets
Perindoprilum argininum + Indapamidum
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

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

Contents of the leaflet:

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

1. What Noliprel Bi-Forte is and what it is used for

Noliprel Bi-Forte is a combination medicine containing two active substances: perindopril and indapamide. It is an antihypertensive medicine used to treat high blood pressure (hypertension). Noliprel Bi-Forte is prescribed to patients who are already receiving 10 mg of perindopril and 2.5 mg of indapamide as separate tablets. These patients may instead take one tablet of Noliprel Bi-Forte containing both components.
Perindopril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors. These medicines work by relaxing blood vessels, making it easier for the heart to pump blood.
Indapamide is a diuretic medicine. Diuretics increase the amount of urine produced by the kidneys. Indapamide differs from other diuretics in that it increases urine output only to a small extent.
Both active substances lower blood pressure and work together to help normalize the patient's blood pressure.

2. Important information before using Noliprel Bi-Forte

When not to use Noliprel Bi-Forte:

• 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 the patient previously experienced symptoms such as wheezing, facial or tongue swelling, intense itching, or severe skin rash while taking an ACE inhibitor, or if such symptoms occurred in the patient or a blood relative under any circumstances (a condition known as angioedema);
• if the patient has diabetes or kidney dysfunction 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 (a brain disorder caused by liver disease);
• if the patient has kidney disease causing reduced blood flow to the kidneys (renal artery stenosis);
• if the patient is undergoing dialysis or another form of blood filtration. Depending on the equipment used, Noliprel Bi-Forte may not be suitable for the patient;
• if the patient has low potassium levels in the blood;
• if the patient is suspected of having untreated, uncompensated heart failure (severe fluid retention, difficulty breathing);
• if the patient is pregnant beyond the 3rd month of pregnancy (it is also advisable to avoid using Noliprel Bi-Forte in early pregnancy – see "Pregnancy");
• if the patient has taken or is currently taking a combination medicine containing sacubitril and valsartan, used to treat heart failure, as this increases the risk of angioedema (rapid swelling of tissues under the skin in the throat area) (see "Warnings and precautions" and "Noliprel Bi-Forte and other medicines").

Warnings and precautions
Before starting Noliprel Bi-Forte, 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 disorder), or renal artery stenzone (narrowing of the blood vessel supplying blood to the kidney);
• if the patient has heart failure or any other heart disease;
• if the patient has kidney disease or is undergoing dialysis;
• if the patient experiences vision disturbances or eye pain. These may be symptoms of fluid accumulation in the choroid layer of the eye (choroidal effusion) or increased intraocular pressure, which may occur within hours or weeks of taking Noliprel Bi-Forte. 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.
• if the patient has muscle disorders, including muscle pain, tenderness, weakness, or cramps;
• if the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• if the patient has liver disease;
• if the patient has a collagen disease (skin disorder), such as systemic lupus erythematosus or scleroderma;
• if the patient has atherosclerosis (hardening of the arteries);
• if the patient has hyperparathyroidism (overactive parathyroid glands);
• if the patient has gout;
• if the patient has diabetes;
• if the patient is on a low-salt diet or uses potassium-containing salt substitutes;
• if the patient is taking lithium or potassium-sparing medicines (spironolactone, triamterene), or potassium supplements – these should be avoided while taking Noliprel Bi-Forte (see "Noliprel Bi-Forte and other medicines");
• if the patient is elderly;
• if the patient has previously experienced photosensitivity reactions;
• if the patient develops a severe allergic reaction with swelling of the face, lips, mouth, tongue, or throat, causing difficulty swallowing or breathing (angioedema) – swelling may occur at any time during treatment. If such symptoms occur, treatment must be stopped immediately and medical advice sought without delay;
• if 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 Bi-Forte".
• 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;
• if the patient is undergoing dialysis using high-permeability membranes;
• if 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 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 the 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 Noliprel Bi-Forte. This reaction may occur at any time during treatment. If such symptoms occur, the patient must stop taking Noliprel Bi-Forte immediately and contact a doctor without delay. See also section 4.
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Use of Noliprel Bi-Forte 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").
When taking Noliprel Bi-Forte, you should also inform your doctor or medical staff:

• if you are scheduled for anaesthesia and/or surgery;
• if you have recently had diarrhoea or vomiting, or if you have been dehydrated;
• if dialysis or LDL apheresis (removal of cholesterol from blood using a special device) is planned;
• if desensitisation treatment is planned to reduce allergic reactions to bee or wasp stings;
• if an imaging test requiring iodine-containing contrast agent (a substance allowing organs such as the kidney or stomach to be visualised in X-ray examinations) is to be performed;
• if you experience vision disturbances or eye pain in one or both eyes during treatment with Noliprel Bi-Forte. These may be symptoms of glaucoma or increased pressure in one or both eyes. You should stop taking Noliprel Bi-Forte and consult a doctor.

Athletes should be aware that Noliprel Bi-Forte contains an active substance (indapamide) that may lead to a positive result in anti-doping tests.
Children and adolescents
Noliprel Bi-Forte must not be used in children and adolescents.
Noliprel Bi-Forte and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Noliprel Bi-Forte must not be used together 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 dysfunction;
• 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 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 (ACE) inhibitors and angiotensin II receptor antagonists.

Other medicines may affect treatment with Noliprel Bi-Forte. Your doctor may recommend dose adjustments and/or additional precautions. Inform your doctor if you are taking any of the following medicines, as special caution may be required:

• other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (AIIRAs) or aliskiren (see also sections "When not to use Noliprel Bi-Forte" 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 of 12.5 mg to 50 mg per day;
• medicines most commonly used to treat diarrhoea (racecadotril) or to prevent organ transplant rejection (sirolimus, everolimus, temsirolimus, and other medicines belonging to the group 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 Bi-Forte" and "Warnings and precautions".
• anaesthetics;
• iodine-containing contrast agents;
• antibiotics used to treat bacterial infections (e.g. moxifloxacin, sparfloxacin, intravenous erythromycin);
• 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 transplant rejection (e.g. cyclosporine, tacrolimus);
• halofantrine (used to treat certain types of malaria);
• pentamidine (used to treat pneumonia);
• injectable gold salts (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 to treat 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 (the substance found 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 Bi-Forte with food and drink
It is recommended to take Noliprel Bi-Forte before a meal.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, you should consult your doctor or pharmacist before using this medicine.
Pregnancy
Your doctor will usually advise stopping Noliprel Bi-Forte before becoming pregnant or as soon as pregnancy is confirmed, and will recommend an alternative medicine.
Noliprel Bi-Forte 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
Noliprel Bi-Forte is not recommended for breastfeeding mothers. Your doctor may choose an alternative treatment if you plan to breastfeed, especially if the baby is a newborn or was born prematurely.
Contact your doctor immediately.
Driving and using machines
Noliprel Bi-Forte usually does not affect alertness; however, some patients may experience side effects such as dizziness or weakness due to lowered blood pressure. In such cases, the ability to drive or operate machinery may be impaired.
Noliprel Bi-Forte contains lactose (a type of sugar)
If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.
Noliprel Bi-Forte contains sodium
Noliprel Bi-Forte contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to use Noliprel Bi-Forte

This medicine should always be taken exactly as directed by your doctor or pharmacist.
If in doubt, consult your doctor or pharmacist.
The recommended dose is one tablet once daily. The tablet should preferably be taken in the morning, before a meal. Swallow the tablet with a glass of water.

Taking more Noliprel Bi-Forte than recommended
If you take too many tablets, contact your doctor immediately or go to the nearest hospital emergency department. The most common 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 your legs raised may help.

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

Stopping Noliprel Bi-Forte
Treatment of high blood pressure is usually long-term; therefore, discuss with your doctor before stopping this medicine.
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 experiences them.
If any of the following adverse reactions, which may be serious, occur in the patient, the medicine must be discontinued immediately and the patient should contact a doctor without delay:

• 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 be a sign of 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 pain, particularly if the patient also feels unwell or has a high temperature, which may be due to abnormal muscle breakdown (frequency unknown).

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

• Common (may occur in less than 1 in 10 patients): low potassium levels in the blood, skin reactions in patients with a tendency to allergic or asthmatic reactions, headache, central dizziness, labyrinthine dizziness, prickling and tingling sensations, visual disturbances, tinnitus (sensation of hearing sounds), cough, shortness of breath, gastrointestinal disturbances (nausea, vomiting, abdominal pain, taste disturbances, indigestion or digestive disorders, 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, depression, sleep disturbances, urticaria, purpura (small red spots on the skin), clusters of blisters, kidney disorders, impotence (inability to achieve or maintain an erection), excessive sweating, increased number of eosinophils (a type of white blood cell), changes in laboratory test results: high potassium levels in the blood, which resolve after stopping treatment, low sodium levels in the blood, which may lead to dehydration and low blood pressure, drowsiness, fainting, palpitations (awareness of heart beating), tachycardia (fast heart rate), 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: low chloride levels in the blood, low magnesium levels in the blood, increased liver enzyme activity, high serum bilirubin levels; fatigue, sudden flushing of the face and neck, reduced or absent urine output, acute kidney failure. Dark-coloured urine, nausea or vomiting, muscle cramps, confusion and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion).
• Very rare (may occur in less than 1 in 10,000 patients): confusion, eosinophilic pneumonia (a rare type of lung inflammation), rhinitis (nasal congestion or runny nose), severe kidney diseases, blood parameter changes such as decreased number of white and red blood cells, decreased haemoglobin concentration, decreased platelet count, high calcium levels in the blood, liver function disorders.
• Frequency not known (cannot be estimated from available data): abnormal heart function detected on ECG, changes in laboratory test results: high uric acid levels and high blood sugar levels, myopia, blurred vision, visual disturbances, worsening of vision or eye pain due to high pressure (possible symptoms of fluid accumulation in the choroidal 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.

If any of these symptoms occur, contact a doctor as soon as possible.

Reporting of adverse reactions

If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 authorization holder.

By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Noliprel Bi-Forte

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following the abbreviation
"EXP" (the abbreviation used to describe the expiry date). The expiry date refers to the last day
of the stated month. The word "Lot" on the packaging indicates the medicine's batch number.
Store in the original packaging, tightly closed, to protect from moisture.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via the sewage system or household waste. Ask your
pharmacist how to dispose of medicines no longer required. Such measures will help protect
the environment.

6. Contents of the package and other information

What Noliprel Bi-Forte contains

• The active substances are: perindopril arginine and indapamide. One coated tablet contains 10 mg of perindopril arginine (equivalent to 6.79 mg of perindopril) and 2.5 mg of indapamide.
• Other components of the tablet are: core – monohydrate lactose, magnesium stearate, maltodextrin, anhydrous colloidal silicon dioxide, sodium carboxymethyl starch (type A); coating – glycerol, hypromellose, polyethylene glycol 6000, magnesium stearate, titanium dioxide (E 171).

What Noliprel Bi-Forte looks like and contents of the pack
Noliprel Bi-Forte is a white, round coated tablet with a diameter of 8 mm and a curvature radius of 11 mm. Each coated tablet contains 10 mg of perindopril arginine and 2.5 mg of indapamide.
Pack sizes: 30, 60, 90, 100 tablets.

Marketing Authorisation Holder
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes cedex
France

Manufacturers
Les Laboratoires Servier Industrie
905 route de Saran
45520 Gidy
France
Servier (Ireland) Industries Ltd
Gorey Road
Arklow – Co. Wicklow
Ireland
ANPHARM Przedsiębiorstwo Farmaceutyczne S.A.
Annopol Street 6B
03-236 Warsaw
Poland

This medicinal product is authorised in the European Economic Area countries under the following names:
Belgium PRETERAX 10 mg /2.5 mg
Bulgaria NOLIPREL Bi-FORTE
Cyprus Preterax 10 mg/ 2.5 mg
Czech Republic Prestarium Neo Combi 10 mg/2.5 mg
Estonia NOLITERAX 10mg/2.5mg
Finland COVERSYL COMP NOVUM 10 mg /2.5 mg
France BIPRETERAX 10mg/2,5mg comprimé pelliculé
Greece Preterax 10 mg/2.5 mg
Ireland COVERSYL ARGININE PLUS 10/2.5 mg
Italy NOLITERAX 10/2.5
Latvia NOLITERAX 10mg/2.5mg apvalkotās tablets
Lithuania NOLITERAX 10mg/2.5mg plėvele dengtos tabletės
Luxembourg PRETERAX 10 mg /2.5 mg
Malta COVERSYL PLUS 10 mg/2.5 mg
Netherlands COVERSYL PLUS arg 10 mg /2.5 mg
Poland NOLIPREL Bi-FORTE
Portugal PRETERAX
Romania NOLITERAX 10 mg /2.5 mg
Slovakia NOLIPREL Bi-FORTE A
Slovenia BIONOLIPREL 10mg/2.5mg filmsko obložene tablete

For detailed information, please contact the representative of the Marketing Authorisation Holder:
Servier Polska Sp. z o.o.
Telephone number: (22) 594-90-00