Polpril nebi

Package leaflet: Information for the user

Polpril Nebi, 2.5 mg + 5 mg, hard capsules
Polpril Nebi, 5 mg + 5 mg, hard capsules
Polpril Nebi, 10 mg + 5 mg, hard capsules
Ramiprilum + Nebivololum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

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

Contents of the leaflet

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

1. What Polpril Nebi is and what it is used for

Polpril Nebi is a combination medicine containing two active substances: ramipril and nebivolol.
Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. It works by relaxing blood vessels, which helps the heart pump blood more easily throughout the body.
Nebivolol belongs to a group of medicines called selective beta-blockers (selectively acting on the cardiovascular system). It prevents excessive heart rate and controls the force of contraction of the heart muscle. It also causes blood vessels to dilate, making it easier for the heart to pump blood.
Polpril Nebi is used as replacement therapy in adults for the treatment of:
hypertension (high blood pressure), chronic heart failure (when the heart is unable to pump sufficient blood to the tissues), coronary artery disease (when blood flow to the heart is reduced or blocked), hypertension coexisting with heart failure, and hypertension coexisting with coronary artery disease – in patients whose condition is adequately controlled with individual medicines administered concomitantly at the same doses as contained in the fixed-dose combination product, but given as separate medicines.

2. Important information before using Polpril Nebi

When not to use Polpril Nebi

• if the patient is allergic to ramipril or nebivolol, any other ACE inhibitor (angiotensin-converting enzyme inhibitor), or any of the other ingredients of this medicine (listed in section 6). Symptoms of an allergic reaction may include: rash, difficulty swallowing or breathing, and swelling of the lips, face, throat, or tongue;
• if the patient has ever had a serious allergic reaction called "angioedema". Symptoms include: itching, hives, red spots on the palms, soles, and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing;
• if the patient has undergone dialysis or another type of blood filtration. Depending on the type of equipment used, Polpril Nebi may not be the appropriate medicine;
• if the patient has kidney problems related to reduced blood flow to the kidneys (renal artery stenosis);
• if the patient is more than 3 months pregnant (use of Polpril Nebi is also advised to be avoided in early pregnancy – see section "Pregnancy and breastfeeding");
• if blood pressure is very low or unstable;
• if the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medicine containing aliskiren;
• if the patient has taken or is currently taking sacubitril with valsartan – a medicine used to treat chronic heart failure in adults – because the risk of angioedema (sudden subcutaneous swelling, e.g. in the throat) increases;
• if the patient has severe liver disease or impaired liver function;
• if the patient has acute heart failure or is receiving intravenous treatment (infusion) supporting heart function, e.g. after acute myocardial infarction or cardiogenic shock;
• if the patient has been diagnosed with conduction disorders in the heart (e.g. sick sinus syndrome or atrioventricular block), and does not have a properly functioning pacemaker;
• if the patient has severe breathing difficulties or wheezing;
• if the patient has untreated adrenal gland tumour called pheochromocytoma (chromaffin tumour);
• if the patient has metabolic acidosis (e.g. in diabetic patients when blood glucose levels are very high and blood pH is too acidic);
• if the patient has a very slow heart rate (less than 60 beats per minute before starting treatment);
• if the patient has low blood pressure (systolic pressure – "upper" – below 90 mmHg);
• if the patient has circulatory disorders in the upper or lower limbs.

Do not use Polpril Nebi if any of the above situations apply to the patient. In case of
doubt, consult a doctor before using Polpril Nebi.
Warnings and precautions
Before starting treatment with Polpril Nebi, discuss this with your doctor or pharmacist:

• if the patient has heart diseases (e.g. untreated heart failure – the heart's inability to pump enough blood; abnormally slow heart rate; mild [first-degree] atrioventricular block in the heart; chest pain caused by coronary artery spasm – so-called Prinzmetal's angina, variant angina);
• if the patient has liver or kidney disease;
• if there is a risk of circulatory disorders in the heart or brain in case of sudden drop in blood pressure;
• if the patient is elderly;
• if the patient has lost a significant amount of salt or fluids (due to vomiting, diarrhoea, excessive sweating, low-salt diet, long-term use of diuretics, or dialysis therapy);
• if the patient is taking any of the following medicines, the risk of angioedema (sudden subcutaneous swelling, e.g. in the throat) increases:
• racecadotril (an antidiarrheal medicine),
• sirolimus, everolimus, temsirolimus, and other medicines in the mTOR inhibitor class (used to prevent transplant rejection and in cancer treatment);
• vildagliptin (an antidiabetic medicine);
• if desensitisation treatment for bee or wasp venom (allergy desensitisation) is planned;
• if the patient has elevated potassium levels in the blood (detected in laboratory tests);
• if the patient is taking antihypertensive medicines from the angiotensin II receptor antagonist group (ARBs, so-called "sartans" – e.g. valsartan, telmisartan, irbesartan), especially if the patient has diabetic kidney disease;
• if the patient has a collagen vascular disease (when immune system problems affect collagen in the body), such as scleroderma (a chronic disease primarily affecting the skin) or systemic lupus erythematosus (a long-term inflammatory disease in which the immune system attacks healthy tissues);
• if the patient is of Black race – there is a higher risk of sudden, usually painful, severe swelling of the deep layers of the skin, mainly in the face, and reduced effectiveness of ramipril;
• if the patient has a cough – inform the doctor if it worsens;
• if the patient is to receive anaesthesia. This may be given in connection with a surgical or dental procedure. It may be necessary to discontinue treatment with Polpril Nebi one day before the procedure; in case of doubt, contact the doctor;
• if the patient has circulatory disorders in the hands or feet (e.g. Raynaud's disease or syndrome, muscle cramp-like pains during walking);
• if the patient has diabetes: this medicine does not affect blood glucose levels, but may mask symptoms of low blood sugar (e.g. trembling, rapid heartbeat);
• if the patient has hyperthyroidism: this medicine may mask symptoms of abnormally fast heart rate caused by this disease;
• if the patient has long-term breathing problems;
• skin changes known as psoriasis, as this medicine may worsen symptoms;
• because allergic reactions may be more severe and may require larger doses of medication for treatment.

The patient must inform the doctor if she suspects she is (or might be) pregnant. Use of
Polpril Nebi is not recommended during the first 3 months of pregnancy and may seriously harm the unborn child
if used after the 3rd month of pregnancy (see section "Pregnancy and breastfeeding").
The doctor may recommend monitoring white blood cell count. More frequent monitoring is recommended:

• at the beginning of treatment,
• in patients with impaired kidney function or collagen vascular diseases, or
• when medicines affecting blood cell count are used.

The doctor may recommend regular kidney function tests, blood pressure measurements, and blood electrolyte levels (e.g. potassium).
Children and adolescents
Polpril Nebi is not recommended for use in children and adolescents under 18 years of age due to
lack of data on use in this age group.
Polpril Nebi and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Inform your doctor if you are taking any of the following medicines:

• sacubitril in combination with valsartan – used to treat long-term (chronic) heart failure in adults;
• potassium supplements (including salt substitutes), potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), and other medicines increasing potassium levels in the blood (e.g. trimethoprim and co-trimoxazole (trimethoprim + sulfamethoxazole) used for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection, and heparin, a medicine used to thin the blood to prevent clots). Close monitoring of blood potassium levels is necessary when these medicines are used concomitantly;
• blood pressure-lowering medicines (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) and other substances that may lower blood pressure (e.g. nitrates, rapid consumption of large amounts of alcohol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin);
• diuretics (water tablets), such as furosemide;
• medicines used to treat low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline or adrenaline, isoprenaline, dobutamine or dopamine. The doctor will monitor blood pressure;
• allopurinol (used to reduce uric acid levels in the blood);
• tacrolimus (used to control the body's immune response, enabling acceptance of a transplanted organ);
• steroid medicines for inflammatory conditions, such as prednisolone;
• procainamide (used for heart rhythm disorders);
• anticancer medicines (chemotherapy);
• medicines that may affect blood cell count;
• lithium (used to treat psychiatric disorders) – Polpril Nebi may increase lithium levels in the blood, so the doctor will recommend regular monitoring of lithium levels;
• antidiabetic medicines, such as oral glucose-lowering agents and insulin – Polpril Nebi may reduce blood glucose levels, so blood glucose should be monitored regularly during treatment;
• medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, indomethacin, or acetylsalicylic acid);
• temsirolimus (used to treat cancer);
• medicines most commonly used to prevent rejection of transplanted organs (sirolimus, everolimus, and other medicines belonging to the mTOR inhibitor class). See section "Warnings and precautions";
• medicines used to treat heart rhythm disorders (irregular heartbeat), such as quinidine, hydroquinidine, amiodarone, cibenzoline, flecainide, disopyramide, lidocaine, mexiletine, propafenone;
• diltiazem or verapamil (used to treat high blood pressure or other heart conditions); intravenous verapamil should not be administered during treatment with Polpril Nebi;
• anaesthetics: always inform the anaesthetist that you are taking Polpril Nebi before undergoing anaesthesia;
• digoxin or other medicines called cardiac glycosides (used to treat heart failure);
• other medicines called calcium channel blockers, used to treat high blood pressure or other heart conditions, such as amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine;
• tricyclic antidepressants (used to treat depression), phenothiazines (used to treat psychosis), or barbiturates (used to treat epilepsy);
• amifostine (a protective medicine used during chemotherapy or radiotherapy);
• medicines affecting nevibolol metabolism, i.e. paroxetine, fluoxetine, thioridazine (used to treat depression);
• cimetidine (used to treat stomach hyperacidity).

Polpril Nebi with food, drink and alcohol
Polpril Nebi may be taken with or without food. Capsules should be swallowed whole with liquid. Do not chew or crush them.
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.
A change in treatment to an appropriate alternative should be made before planned pregnancy.
Pregnancy
Polpril Nebi should not be used during pregnancy unless absolutely necessary.
Do not use Polpril Nebi during the first 12 weeks of pregnancy and must not be taken after the 13th week of pregnancy, as it may seriously harm the unborn child. If the patient becomes pregnant while taking Polpril Nebi, she should inform her doctor immediately.
Breastfeeding
Polpril Nebi should not be used during breastfeeding.
Driving and operating machinery
This medicine may cause dizziness or fatigue, especially at the beginning of treatment or after dose increase. If such symptoms occur, do not drive, use tools, or operate machinery.
Polpril Nebi contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, meaning the medicine is considered "sodium-free".

3. How to use Polpril Nebi

This medicine should always be taken exactly as directed by the doctor or pharmacist. If in doubt,
consult the doctor or pharmacist.
Adults
The usual recommended dose of Polpril Nebi is one capsule once daily.
Depending on the response, the doctor may increase or adjust the dose. Do not take a higher dose than prescribed.
Method of administration

• This medicine should be taken orally, at the same time each day, with or without food.
• Capsules should be swallowed whole with liquid.
• Do not chew or crush the capsules.

If the patient feels that the effect of the medicine is too strong or too weak, they should consult the doctor.
Elderly patients
The doctor may use a lower starting dose and adjust treatment more gradually.
Use in children and adolescents
Polpril Nebi is not recommended for use in children and adolescents.
Taking more Polpril Nebi than recommended
Seek immediate medical advice or go to the nearest hospital emergency department.
Do not drive yourself—ask someone to take you to the hospital or call an ambulance.
Bring the medicine packaging with you so the doctor knows which medicine has been taken.
If you miss a dose of Polpril Nebi
If a dose is missed, take the next dose at the usual time. Do not take a double dose to make up for the missed capsule.
Stopping Polpril Nebi
Do not stop taking Polpril Nebi suddenly or change the prescribed dose without consulting your doctor, as this may worsen the condition.
If you have any further doubts 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.
You must stop taking Polpril Nebi and contact your doctor immediately if any of the following serious adverse reactions occur – urgent treatment may be required:

• swelling of the face, lips, tongue or throat causing difficulty swallowing or breathing and (or) itching and rash (uncommon – occurs in no more than 1 in 100 patients);
• severe skin reactions, including rashes, mouth ulcers, worsening of pre-existing skin diseases, redness, blisters or peeling of the outer layer of skin (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme) (frequency unknown).

Contact your doctor immediately if the patient experiences:

• increased potassium levels in blood tests (common – occurs in no more than 1 in 10 patients);
• rapid heartbeat, irregular or stronger heartbeat (palpitations), chest pain, chest tightness or more serious conditions including angina, heart attack (uncommon – occurs in no more than 1 in 100 patients) or stroke (frequency unknown);
• slow heartbeat, heart failure, abnormal ECG (uncommon – occurs in no more than 1 in 100 patients);
• severe abdominal pain which may radiate to the back. This may be a symptom of pancreatitis (uncommon – occurs in no more than 1 in 100 patients);
• easy bruising, prolonged bleeding time, any signs of bleeding (e.g. bleeding gums), purple spots on the skin or increased frequency of infections, sore throat and fever, fatigue, weakness, dizziness or pale skin. These may indicate blood or bone marrow disorders (rare – occurs in no more than 1 in 1,000 patients);
• fever, chills, weakness, loss of appetite, abdominal pain, nausea, yellowing of the skin or whites of the eyes (jaundice). These may be symptoms of liver disorders such as hepatitis or liver damage (frequency unknown);
• concentrated (dark-coloured) urine, nausea or vomiting, muscle cramps, confusion and seizures, which may be caused by abnormal secretion of ADH (antidiuretic hormone) (frequency unknown).

Other adverse reactions
Common (occurs in no more than 1 in 10 patients)

• headache, dizziness;
• skin itching and sensory disturbances such as numbness, tingling, pricking, burning or crawling sensations on the skin (paraesthesia);
• hypotension (abnormally low blood pressure), especially when standing up or sitting down quickly; fainting;
• dry, irritating cough, sinusitis or bronchitis, shortness of breath;
• inflammation of the stomach and (or) intestines, digestive disturbances, indigestion, diarrhoea, constipation, nausea or vomiting;
• rash (with or without raised lesions);
• muscle cramps or pain;
• chest pain;
• fatigue, feeling of exhaustion, swelling.

Uncommon (occurs in no more than 1 in 100 patients)

• increased number of certain white blood cells (eosinophilia) in blood tests;
• loss or decrease of appetite;
• low mood, anxiety, nervousness, restlessness, sleep problems including drowsiness, nightmares, depression;
• balance problems (dizziness);
• loss or change in taste;
• vision disturbances (including blurred vision);
• palpitations (awareness of heartbeat);
• sudden flushing of the face;
• ankle swelling;
• pain in legs or arms occurring during exertion (intermittent claudication);
• difficulty breathing or worsening of asthma, nasal congestion;
• intestinal swelling called "intestinal angioedema" presenting as abdominal pain, vomiting and diarrhoea;
• abdominal pain, dry mouth, bloating;
• blood tests showing changes in pancreas, liver or kidney function;
• skin itching, excessive sweating, erythematous rash;
• joint pain;
• reduced kidney function, increased need to pass urine;
• increased levels of urea or creatinine in blood;
• increased excretion of protein in urine (in laboratory tests);
• impotence (inability to achieve or maintain erection), decreased libido (sex drive in men or women);
• fever.

Rare (occurs in no more than 1 in 1,000 patients)

• decreased number of red blood cells, white blood cells or platelets or haemoglobin concentration as shown in blood tests;
• confusion;
• sensation of trembling or disorientation;
• redness, itching, swelling and watering of the eyes;
• hearing disturbances, tinnitus;
• narrowing of blood vessels, reduced blood flow, inflammation of blood vessels;
• redness, itching, swelling and watering of the eyes;
• red, swollen tongue;
• pain, yellowing of the skin or whites of the eyes (jaundice), liver cell damage;
• severe skin peeling, itchy nodular rash;
• nail disorders (e.g. loosening or separation of the nail from the nail bed);
• malaise, weakness.

Very rare (occurs in no more than 1 in 10,000 patients)

• photosensitivity (increased sensitivity to sunlight);
• worsening of psoriasis (a skin disease with scaly, pink patches).

Frequency unknown (cannot be estimated from available data)

• decreased sodium levels in blood tests;
• difficulty concentrating;
• slowed or impaired reactions, burning sensation, disturbances in smell;
• discolouration, numbness and pain in fingers or toes (Raynaud's phenomenon);
• small ulcers in the mouth;
• blisters that peel off and turn into erosions, large tense blisters; lichenoid eruptions; erythematous and itchy skin changes; mucosal eruptions (exanthema);
• hair loss;
• enlargement of breast glands in men.

For some beta-blockers, the following have also been reported: hallucinations, psychosis, confusion, cold and (or) cyanotic extremities, dry eyes.
Reporting of adverse reactions
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +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.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Polpril Nebi

Keep this medicine out of sight and reach of children.
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the carton and blister pack following "EXP".
The expiry date refers to the last day of the stated month.
The label on the packaging following the abbreviation EXP indicates the expiry date, and following the abbreviation Lot indicates the batch number.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Polpril Nebi contains

• The active substances are ramipril and nebivolol. Each 2.5 mg + 5 mg capsule contains 2.5 mg of ramipril and 5.45 mg of nebivolol hydrochloride, equivalent to 5 mg of nebivolol. Each 5 mg + 5 mg capsule contains 5 mg of ramipril and 5.45 mg of nebivolol hydrochloride, equivalent to 5 mg of nebivolol. Each 10 mg + 5 mg capsule contains 10 mg of ramipril and 5.45 mg of nebivolol hydrochloride, equivalent to 5 mg of nebivolol.
• The other ingredients are: mannitol; maize starch; sodium croscarmellose; hypromellose; polysorbate 80; microcrystalline cellulose; colloidal anhydrous silica; magnesium stearate; pregelatinised maize starch; gelatin; brilliant blue FCF (E133); iron oxide red (E172) (only in 5 mg + 5 mg and 10 mg + 5 mg strengths); iron oxide yellow (E172) (only in 2.5 mg + 5 mg and 5 mg + 5 mg strengths); capsule ink: shellac, iron oxide black (E172), propylene glycol (E1520), ammonium hydroxide 28%.

What Polpril Nebi looks like and contents of the pack
Polpril Nebi 2.5 mg + 5 mg: hard gelatin capsules with a yellow body printed with “2,5+5” and a transparent blue cap (green colour at the joint between cap and body); capsule size - No. 1 (approximately 19.4 mm in length); the capsule contents consist of white or almost white powder and a white or almost white tablet.
Polpril Nebi 5 mg + 5 mg: hard gelatin capsules with an orange body printed with “5+5” and a transparent blue cap (dark green colour at the joint between cap and body); capsule size - No. 1 (approximately 19.4 mm in length); the capsule contents consist of white or almost white powder and a white or almost white tablet.
Polpril Nebi 10 mg + 5 mg: hard gelatin capsules with a dark red body printed with “10+5” and a transparent blue cap (navy blue colour at the joint between cap and body); capsule size - No. 1 (approximately 19.4 mm in length); the capsule contents consist of white or almost white powder and a white or almost white tablet.
Pack size: 30, 60 or 90 capsules in blisters made of Aluminium//OPA/Aluminium/PVC.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański, Poland
tel. +48 22 364 61 01

This medicinal product is authorised in the European Economic Area under the following names:
Bulgaria Полпрен