Prestilol

Package leaflet: Information for the patient

Prestilol
10 mg + 10 mg, film-coated tablets
Bisoprolol fumarate + Perindopril arginine
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

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

Leaflet contents:

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

1. What Prestilol is and what it is used for

Prestilol contains two active substances in one tablet: bisoprolol fumarate and perindopril with arginine.

• Bisoprolol fumarate belongs to a group of medicines called beta-blockers. Beta-blockers slow down the heart rate and make the heart more efficient at pumping blood throughout the body.
• Perindopril with arginine is an angiotensin-converting enzyme (ACE) inhibitor. It works by relaxing blood vessels, which helps the heart pump blood more easily.

Prestilol is used to treat high blood pressure (hypertension) and/or to reduce the risk of cardiac events such as heart attack in patients with stable coronary artery disease (a condition in which blood supply to the heart is reduced or blocked), who have already had a heart attack and/or undergone a surgical procedure to improve blood supply to the heart by widening the blood vessels that supply it.
Instead of taking bisoprolol fumarate and perindopril with arginine as separate tablets, the patient will take only one Prestilol tablet containing both active substances in the same amounts.

2. Important information before using Prestilol

When not to use Prestilol:

• if the patient is allergic to bisoprolol or any other beta-blocker, to perindopril or any other ACE inhibitor, or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has heart failure which has suddenly worsened and (or) requires hospital treatment;
• if the patient has cardiogenic shock (a severe heart condition causing very low blood pressure);
• if the patient has a heart disease characterised by slow or irregular heartbeat (second- or third-degree atrioventricular block, sinoatrial block, sick sinus syndrome);
• if the patient has a slow heart rate;
• if the patient has very low blood pressure;
• if the patient has severe asthma or severe chronic lung disease;
• if the patient has severe circulation problems in the limbs (such as Raynaud's syndrome), which may cause tingling, paleness or blueness of fingers and toes;
• if the patient has untreated phaeochromocytoma, a rare tumour of the adrenal gland;
• if the patient has metabolic acidosis, a condition in which the blood contains too much acid;
• if during previous treatment with an ACE inhibitor the patient experienced symptoms such as: wheezing, swelling of the face, tongue or throat, severe itching or severe skin rash, or if such symptoms occurred in a blood relative under any circumstances (a condition called angioedema);
• if the patient is more than 3 months pregnant (it is also advisable to avoid using Prestilol during 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 blood filtration by another method. Depending on the device used, Prestilol may not be suitable for the patient;
• if the patient has kidney disorders causing reduced blood supply to the kidneys (renal artery stenosis);
• if the patient has taken or is currently taking a combination medicine containing sacubitril and valsartan, used to treat 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 "Prestilol with other medicines").

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

• the patient has diabetes;
• the patient has kidney problems (this also applies to patients who have had a kidney transplant) or is undergoing dialysis;
• there are liver disorders;
• the patient has been diagnosed with aortic or mitral valve stenosis (narrowing of the main blood vessel leading from the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of arteries supplying blood to the kidneys);
• the patient has abnormally increased levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• the patient has heart failure or any other heart disease, such as heart rhythm disorders or severe chest pain at rest (Prinzmetal's angina);
• the patient has been diagnosed with collagenosis (connective tissue disease), such as systemic lupus erythematosus or scleroderma;
• the patient is on a low-salt diet or uses salt substitutes containing potassium (high potassium levels in the blood may cause changes in heart rate);
• the patient has recently had diarrhoea or vomiting, or is dehydrated (Prestilol may cause a drop in blood pressure);
• the patient is undergoing LDL apheresis (removal of cholesterol from the blood using a special device);
• the patient is undergoing desensitisation treatment to reduce allergic reactions to bee or wasp stings;
• the patient is fasting or on a diet;
• the patient is undergoing anaesthesia and (or) surgery;
• the patient has circulation problems in the limbs;
• the patient has asthma or chronic lung disease;
• the patient has (or has had) psoriasis;
• the patient has an adrenal gland tumour (phaeochromocytoma);
• the patient has thyroid disorders (Prestilol may mask symptoms of hyperthyroidism);
• angioedema occurs (a severe allergic reaction characterised by: swelling of the face, lips, tongue or throat, difficulty swallowing or breathing). This reaction may occur at any time during treatment. If such symptoms occur, the patient must stop taking Prestilol and contact a doctor immediately;
• in patients of Black race, there is a higher risk of developing angioedema, and this medicine may be less effective in lowering blood pressure than in patients of other races;
• the patient is taking any of the following medicines used to treat high blood pressure:
  • an angiotensin II receptor antagonist (ARB) (also known as sartans - e.g. valsartan, telmisartan, irbesartan), especially if the patient has kidney problems related to diabetes;
  • aliskiren. The treating 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 Prestilol".
• 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 a group 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 a group called gliptins (used to treat diabetes).

Do not suddenly stop taking Prestilol, as this may cause a severe worsening of heart function. Treatment should not be stopped abruptly, especially in patients with coronary artery disease.
The patient must inform the doctor if she thinks she is (or might be) pregnant. Prestilol is not recommended during early pregnancy and must not be taken if the patient is more than 3 months pregnant, as the medicine may cause serious harm to the unborn child if used during this period (see section "Pregnacy").

Children and adolescents
Prestilol is not recommended for children and adolescents under 18 years of age.

Prestilol with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
The effect of Prestilol may be influenced by other medicines, or Prestilol may alter the effect of other medicines. This type of interaction may cause one or both medicines to be less effective. It may also increase the risk or severity of side effects.
Tell your doctor if the patient is taking any of the following medicines:

• medicines used to control blood pressure or heart conditions (such as amiodarone, amlodipine, clonidine, cardiac glycosides, diltiazem, disopyramide, felodipine, flecainide, lidocaine, methyldopa, moxonidine, procainamide, propafenone, quinidine, rilmenidine, verapamil);
• other medicines used to treat high blood pressure, including angiotensin II receptor antagonists (ARBs), aliskiren (see also information under the headings "When not to use Prestilol" and "Warnings and precautions") or diuretics (medicines that increase urine production by the kidneys);
• potassium-sparing medicines (e.g. triamterene, amiloride), potassium supplements or salt substitutes containing potassium, 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);
• potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone at doses from 12.5 mg to 50 mg per day;
• sympathomimetic medicines used to treat shock (adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine);
• estramustine used to treat cancer;
• 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 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 Prestilol" and "Warnings and precautions".
• lithium used to treat mania or depression;
• certain medicines used to treat depression, such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAO inhibitors; except MAO-B inhibitors);
• certain medicines used to treat schizophrenia (antipsychotics);
• certain medicines used to treat epilepsy (phenytoin, barbiturates such as phenobarbital);
• anaesthetics used during surgical procedures;
• vasodilators, including nitrates (medicines that cause blood vessels to widen);
• trimethoprim used to treat infections;
• immunosuppressive medicines (reducing the body's immune response), such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after organ transplantation;
• allopurinol used to treat gout;
• parasympathomimetic medicines used to treat conditions such as Alzheimer's disease or glaucoma;
• locally administered beta-blockers used to treat glaucoma (increased eye pressure);
• mefloquine used to prevent or treat malaria;
• baclofen used to treat muscle stiffness in conditions such as multiple sclerosis;
• gold salts, particularly administered intravenously (used to treat symptoms of rheumatoid arthritis);
• medicines used to treat diabetes, such as insulin, metformin, linagliptin, saxagliptin, sitagliptin, vildagliptin;
• non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac or high doses of acetylsalicylic acid, used to treat joint inflammation, headache, pain or inflammatory conditions.

Prestilol with food and drink
It is recommended to take Prestilol before meals.

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

Pregnancy
The patient must inform the doctor if she thinks she is (or might be) pregnant. Usually, the doctor will recommend stopping Prestilol before becoming pregnant or as soon as pregnancy is confirmed, and will recommend an alternative medicine. Prestilol is not recommended during early pregnancy and must not be taken if the patient is more than 3 months pregnant, as the medicine may cause serious harm to the unborn child if used after the third month of pregnancy.

Breastfeeding
Inform the doctor if the patient is breastfeeding or starts breastfeeding. Prestilol is not recommended for 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 operating machinery
Prestilol usually does not affect alertness, but some patients may experience dizziness or weakness related to low blood pressure, especially at the beginning of treatment, after a dose change, or when combined with alcohol. In such cases, the ability to drive or operate machinery may be impaired.

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

3. How to use Prestilol

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
The recommended dose is one tablet once daily. The tablet should be swallowed with a glass of water, in the morning
before a meal.
Patients with kidney disease
Prestilol is not recommended for patients with moderate or severe kidney disease.
Use in children and adolescents
Use in children and adolescents is not recommended.
Taking more Prestilol than recommended
If you take more tablets than recommended, contact your doctor or pharmacist immediately.
The most likely symptom of overdose is low blood pressure, which may cause dizziness or fainting (if this occurs, placing the patient with elevated legs may be helpful), severe breathing difficulties, tremor (due to reduced blood sugar concentration), and slowed heart rate.
Missing a dose of Prestilol
It is important to take the medicine regularly every day, as this ensures better effectiveness. However, if a dose of Prestilol is missed, the next dose should be taken at the usual time. Do not take a double dose to make up for a forgotten dose.
Stopping treatment with Prestilol
Do not suddenly stop treatment with Prestilol or change the dose without consulting your doctor, as this may lead to a significant worsening of heart function. Do not abruptly discontinue therapy, especially in patients with coronary artery disease.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

• severe dizziness or fainting caused by low blood pressure (common – may occur in up to 1 in 10 patients);
• worsening of heart failure causing significant shortness of breath and/or fluid retention in the body (common – may occur in up to 1 in 10 patients);
• swelling of the face, lips, mouth, tongue or throat, breathing difficulties (angioedema; uncommon – may occur in up to 1 in 100 patients);
• sudden onset of wheezing, chest pain, shortness of breath or breathing difficulties (bronchospasm; uncommon – may occur in up to 1 in 100 patients);
• extremely rapid or irregular heartbeat, chest pain (angina pectoris) or heart attack (very rare – may occur in up to 1 in 10,000 patients);
• muscle weakness in the arms or legs, or difficulty speaking, which may be signs of stroke (very rare – may occur in up to 1 in 10,000 patients);
• inflammation of the pancreas, which may cause severe abdominal pain radiating to the back and general malaise (very rare – may occur in up to 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 up to 1 in 10,000 patients);
• rash, often beginning with red, itchy spots on the face, arms or legs (erythema multiforme; very rare – may occur in up to 1 in 10,000 patients).

Prestilol is generally well tolerated, but as with other medicines, patients may experience various adverse effects, especially at the beginning of treatment.
You should immediately inform your doctor or pharmacist if any of the following adverse effects
occur in the patient:

Very common (may occur in more than 1 in 10 patients):

• slow heartbeat.

Common (may occur in up to 1 in 10 patients):

• headache;
• central dizziness;
• labyrinthine dizziness;
• taste disturbances;
• tingling;
• numbness of hands or feet;
• visual disturbances;
• tinnitus (sensation of hearing sounds);
• sensation of coldness in hands or feet;
• cough;
• shortness of breath;
• gastrointestinal disturbances such as nausea, vomiting, abdominal pain, indigestion or difficulty digesting, diarrhoea, constipation;
• allergic reactions such as rashes, itching;
• painful muscle cramps;
• feeling of fatigue;
• tiredness.

Uncommon (may occur in up to 1 in 100 patients):

• mood changes;
• sleep disturbances;
• depression;
• dry mouth;
• severe itching or severe rashes;
• formation of blister clusters on the skin;
• increased skin sensitivity to light (photosensitivity reaction);
• sweating;
• kidney disorders;
• impotence;
• increased eosinophil count (a type of white blood cell);
• drowsiness;
• fainting;
• palpitations;
• tachycardia;
• irregular heart rate (atrioventricular conduction disturbances);
• vasculitis;
• dizziness upon standing;
• muscle weakness;
• joint pain;
• muscle pain;
• chest pain;
• malaise;
• peripheral oedema;
• fever;
• falls;
• changes in laboratory test results: high blood potassium levels, which resolve after discontinuation of treatment, low sodium levels, hypoglycaemia (very low blood sugar) in diabetic patients, increased blood urea levels, increased blood creatinine levels.

Rare (may occur in up to 1 in 1,000 patients):

• acute kidney failure;
• dark urine, nausea or vomiting, muscle cramps, confusion and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion);
• reduced or absent urine output;
• sudden redness of the face and neck;
• nightmares, hallucinations;
• decreased tear secretion (dry eyes);
• hearing problems;
• liver inflammation, which may cause yellowing of the skin or whites of the eyes;
• allergic rhinitis, sneezing;
• allergy-like reactions: itching, hot flushes, rash;
• exacerbation of psoriasis;
• changes in laboratory test results: increased liver enzyme activity, high serum bilirubin levels, abnormal blood lipid levels.

Very rare (may occur in up to 1 in 10,000 patients):

• disorientation;
• eye irritation and redness (conjunctivitis);
• eosinophilic pneumonia (a rare type of lung inflammation);
• pancreatitis (which may cause severe upper abdominal pain radiating to the back);
• hair loss;
• onset or worsening of psoriasis, psoriasiform rash;
• blood count changes such as reduced white blood cell and red blood cell counts, reduced haemoglobin levels, reduced platelet count.

Frequency not known (cannot be estimated from available data):

• bluish discoloration, numbness and pain in fingers of hands or feet (Raynaud's phenomenon).

If any of these symptoms occur, you should contact your doctor as soon as possible.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. 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
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Prestilol

Keep the medicine out of the 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 batch number of the medicine.
No special storage conditions are required for this medicinal product.
After first opening the tablet container containing 30 coated tablets of Prestilol,
the product should be used within 60 days.
After first opening the tablet container containing 100 coated tablets of Prestilol,
the product should be used within 100 days.
Medicines must not be disposed of via sewage systems or household waste. Ask your
pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the pack and other information

What Prestilol contains

• The active substances are bisoprolol fumarate and perindopril arginine. Each tablet of Prestilol contains 10 mg of bisoprolol fumarate, equivalent to 8.49 mg of bisoprolol, and 10 mg of perindopril with arginine, equivalent to 6.790 mg of perindopril.
• The other ingredients are: microcrystalline cellulose PH 102, calcium carbonate, gelatinized corn starch, sodium carboxymethyl starch (type A), colloidal anhydrous silica, magnesium stearate, sodium croscarmellose, glycerol, hypromellose, macrogol 6000, titanium dioxide (E171),
  iron oxide yellow (E172), iron oxide red (E172).
  What Prestilol looks like and contents of the pack
  Prestilol is a pink-beige, elongated, two-layer, film-coated tablet, marked with “ ”

on one side and “10/10” on the other side of the tablet.
Tablets are available in containers containing 30, 90 (3 containers of 30 tablets each) or 100 tablets,
packaged in cardboard boxes.
Not all pack sizes may be marketed.
Marketing Authorisation Holder:
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes cedex
France
Manufacturer:
Les Laboratoires Servier Industrie (LSI)
905 route de Saran
45520 Gidy
France
Servier (Ireland) Industries Ltd (SII)
Moneylands, Gorey Road
Arklow - Co. Wicklow
Ireland
Anpharm Przedsiębiorstwo Farmaceutyczne S.A.
Annopol 6B
03-236 Warsaw
EGIS Pharmaceuticals PLC
Mátyás király u. 65
H-9900 Körmend
Hungary
For detailed information, please contact the representative of the Marketing Authorisation Holder:
Servier Polska Sp. z o.o.
Telephone number: (22) 594 90 00
This medicinal product is authorised for marketing in the European Economic Area under the following names:
Belgium Bipressil 10 mg/10 mg comprimé pelliculé
Bulgaria Prestilol 10 mg/10 mg film-coated tablets
Cyprus Cosyrel 10 mg/10 mg film-coated tablets
Czech Republic Cosyrel 10 mg/10 mg, potahované tablety
Estonia Prestilol
Finland Cosyrel 10 mg/10 mg Tabletti, kalvopäällysteinen
France Cosimprel 10 mg/10 mg, comprimé pelliculé
Greece Cosyrel 10 mg/10 mg επικαλυμμένα με λεπτό υμένιο δισκία
Hungary Cosyrel 10 mg/10 mg filmtabletta
Ireland Cosimprel 10 mg/10 mg film-coated tablet
Italy Cosyrel
Latvia Prestilol 10 mg/10 mg apvalkotās tabletes
Lithuania Cosimprel 10 mg/10 mg plėvele dengtos tabletės
Luxembourg Bipressil 10 mg/10 mg comprimé pelliculé
Netherlands Cosimprel 10 mg/10 mg filmomhulde tabletten
Poland Prestilol
Portugal Cosyrel 10 mg/10 mg
Romania Cosyrel 10 mg/10 mg comprimate filmate
Slovakia Prestilol 10 mg/10 mg filmom obalené tablety
Slovenia Cosyrel 10 mg/10 mg filmsko obložene tablete