Biprindo

Patient Information Leaflet

Biprindo, 5 mg + 5 mg, film-coated tablets
Bisoprolol fumarate + Perindopril arginine
Please read the entire leaflet carefully before using this medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are similar.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

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

1. What Biprindo is and what it is used for

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

• Bisoprolol fumarate belongs to a group of medicines called beta-blockers. Beta-blockers reduce heart rate and make the heart pump blood more efficiently throughout the body.
• Perindopril arginine is an angiotensin-converting enzyme (ACE) inhibitor. It works by dilating blood vessels, making it easier for the heart to pump blood.

Biprindo is used to treat high blood pressure (hypertension) and/or chronic stable heart failure (a condition in which the heart is unable to pump enough blood to meet the body's needs, leading to breathlessness and swelling), and/or to reduce the risk of cardiovascular events such as myocardial infarction (heart attack) in patients with stable coronary artery disease (a condition in which blood supply to the heart is reduced or blocked), who have previously had a heart attack and/or undergone a surgical procedure to improve blood supply to the heart by widening the blood vessels that deliver blood to it.

2. Important information before using Biprindo

When not to use Biprindo

• 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 caused by very low blood pressure);
• if the patient has a heart disease characterized 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 circulatory disorders 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 the patient or a blood relative under any other circumstances (a condition called angioedema);
• if the patient is more than 3 months pregnant (it is also advisable to avoid using Biprindo in early pregnancy - see section "Pregnancy");
• if the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren;
• if the patient is undergoing dialysis or other blood filtration methods. Depending on the device used, Biprindo 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 in the treatment of 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 "Biprindo with other medicines").

Warnings and precautions
Before starting Biprindo, discuss this with your doctor or pharmacist:

• if the patient has diabetes;
• if the patient has kidney disorders (this also applies to patients after kidney transplantation) or if the patient is undergoing dialysis;
• if the patient has liver disorders;
• if 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 the artery supplying blood to the kidney);
• if the patient has abnormally high levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• if the patient has heart failure or any other heart diseases, such as heart rhythm disorders or severe chest pain at rest (Prinzmetal's angina);
• if the patient has been diagnosed with collagenosis (connective tissue disease), such as systemic lupus erythematosus or scleroderma;
• if the patient is on a low-salt diet or uses salt substitutes containing potassium (excess potassium in the blood may cause changes in heart rate);
• if the patient has recently had diarrhoea or vomiting, or if the patient is dehydrated (Biprindo may cause a drop in blood pressure);
• if the patient is undergoing LDL apheresis (removal of cholesterol from the blood using a special device), is currently receiving antiallergic treatment, or is about to undergo desensitisation treatment to reduce allergic reactions to bee or wasp stings;
• if the patient is fasting or on a diet;
• if the patient is about to undergo anaesthesia and (or) surgery;
• if the patient has circulatory disorders in the limbs;
• if the patient has asthma or chronic lung disease;
• if the patient has (or has had) psoriasis;
• if the patient has an adrenal gland tumour (phaeochromocytoma);
• if the patient has thyroid disorders (Biprindo may mask symptoms of hyperthyroidism);
• if the patient has angioedema (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, stop taking Biprindo and contact your doctor immediately;
• in black patients, there is a higher risk of angioedema, and this medicine may be less effective in lowering blood pressure than in patients of other races;
• if 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 disorders related to diabetes;
• aliskiren. Your 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 Biprindo".
• if the patient is taking any of the following medicines, the risk of angioedema increases:
• racecadotril (used to treat diarrhoea);
• sirolimus, everolimus, temsirolimus and other medicines belonging to the group of drugs known as mTOR inhibitors (used to prevent rejection of transplanted organs and in cancer treatment);
• sacubitril (available in a combination medicine containing sacubitril and valsartan), used in the treatment of chronic heart failure;
• linagliptin, saxagliptin, sitagliptin, vildagliptin and other medicines belonging to the group of drugs known as gliptins (used in the treatment of diabetes).

Do not suddenly stop taking Biprindo, as this may cause a severe worsening of heart function. Treatment should not be suddenly discontinued, especially in patients with coronary artery disease.
The patient should inform the doctor if she thinks she is (or might be) pregnant. Biprindo is not recommended in 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 time (see section "Pregnancy").
Children and adolescents
Biprindo is not recommended for use in children and adolescents under 18 years of age.
Biprindo with 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.
Other medicines may affect the action of Biprindo or Biprindo may alter the action 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 adverse 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, digitalis 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 Biprindo" 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 blood clots;
trimethoprim and co-trimoxazole, also known as a combination medicine containing trimethoprim
and sulfamethoxazole, used to treat bacterial infections);

• potassium-sparing medicines used in the treatment of heart failure: eplerenone and spironolactone at doses of 12.5 mg to 50 mg per day;
• sympathomimetic medicines used to treat shock (adrenaline, noradrenaline, dobutamine, isoprenaline, ephedrine);
• estramustine used in the treatment of 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 of drugs known as mTOR inhibitors). See section "Warnings and precautions".
• a combination medicine containing sacubitril and valsartan (used in the treatment of chronic heart failure). See sections "When not to use Biprindo" 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 in surgical procedures;
• vasodilators, including nitrates (medicines that cause blood vessels to widen); trimethoprim used to treat infections;
• immunosuppressive medicines (reducing the body's immune responses), such as cyclosporine, tacrolimus, used in the treatment of 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, especially when 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.

Biprindo with food and drink
It is recommended to take the combination medicine containing bisoprolol and perindopril before a meal.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant or plans to have a child, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
The patient should inform the doctor if she thinks she is (or might be) pregnant. Usually, the doctor will recommend discontinuing Biprindo before becoming pregnant or as soon as pregnancy is confirmed and will recommend another medicine instead of Biprindo. Biprindo is not recommended in 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 about to start breastfeeding. Biprindo is not recommended for use in breastfeeding mothers, and the doctor may choose another treatment method if the patient wishes to breastfeed, especially if the baby is a newborn or was born prematurely.
Driving and operating machinery
Biprindo usually does not affect alertness, but some patients may experience dizziness or weakness related to low blood pressure, especially at the beginning of treatment or after a dose change or in combination with alcohol. In such cases, the ability to drive or operate machinery may be impaired.
Biprindo contains sodium and lactose
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult the doctor before taking the medicine.
3. How to take Biprindo
This medicine should always be taken exactly as prescribed by the doctor or pharmacist. If in doubt, consult the 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.
In some cases, the doctor may recommend half a tablet of Biprindo once daily, taken in the morning before a meal.
Kidney function disorders
If the patient has moderate kidney disease, the doctor may recommend half a tablet of Biprindo. Biprindo is not recommended for patients with severe kidney disease.
Use in children and adolescents
Use in children and adolescents is not recommended.
Taking more Biprindo than recommended
If too many tablets are taken, contact a doctor or pharmacist immediately.
The most likely symptom of overdose is low blood pressure, which may cause dizziness or fainting (if this occurs, it may help to lie the patient down with legs raised), severe breathing difficulties, tremor (due to low blood sugar levels) and slow heart rate.
Missing a dose of Biprindo
It is important to take the medicine regularly every day, as this ensures better effectiveness. However, if a dose of Biprindo is missed, take the next dose at the usual time.
Do not take a double dose to make up for a missed dose.
Stopping Biprindo treatment
Do not suddenly stop taking Biprindo or change the dose without consulting a doctor, as this may cause a significant worsening of heart function. Do not suddenly stop treatment, especially in patients with coronary artery disease.
If you have any further doubts regarding 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 this medicine and contact your doctor immediately if any of the following adverse reactions 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, difficulty breathing (angioedema) (uncommon – may occur in up to 1 in 100 patients);
• sudden onset of wheezing, chest pain, shortness of breath or difficulty breathing (bronchospasm) (uncommon – may occur in up to 1 in 100 patients);
• extremely rapid or irregular heartbeat, chest pain (angina) or heart attack (very rare – may occur in up to 1 in 10,000 patients);
• muscle weakness in 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).

Biprindo is generally well tolerated, but as with other medicines, patients may experience various adverse reactions, especially at the beginning of treatment.
You should immediately inform your doctor or pharmacist if any of the following adverse reactions occur, or any other, not listed below:
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 origin dizziness;
• labyrinthine origin dizziness;
• taste disturbances;
• tingling;
• numbness of hands or feet;
• vision 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, diarrhea, 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 clusters of blisters on the skin;
• increased sensitivity of the skin to light (photosensitivity reaction);
• sweating;
• kidney disorders;
• impotence;
• increased number of eosinophils (a type of white blood cells);
• drowsiness;
• fainting;
• palpitations;
• tachycardia;
• irregular heart rate (atrioventricular conduction disturbances);
• vasculitis (inflammation of blood vessels);
• dizziness upon standing;
• muscle weakness;
• joint pain;
• muscle pain;
• chest pain;
• malaise;
• peripheral edema;
• fever;
• falls;
• altered laboratory test results: high blood potassium levels, transient and resolving after discontinuation of treatment, low sodium levels, hypoglycemia (very low blood sugar levels) 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 production (dry eyes);
• hearing problems;
• liver inflammation, possibly causing yellowing of the skin or whites of the eyes;
• allergic rhinitis, sneezing;
• allergy-like reactions: itching, hot flushes, rash;
• exacerbation of psoriasis;
• altered 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):

• confusion;
• 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, psoriasis-like rash;
• blood count changes such as decreased number of white and red blood cells, decreased hemoglobin concentration, decreased platelet count.

Frequency unknown (cannot be estimated from the available data):

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

If any of these symptoms occur, you should contact your doctor as soon as possible.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products 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 reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Biprindo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the word EXP. The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from moisture.
There are no special storage temperature requirements for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. Such measures will help protect the environment.

6. Contents of the pack and other information

What Biprindo contains

• The active substances are bisoprolol fumarate and perindopril arginine. Each tablet contains 5 mg of bisoprolol fumarate (equivalent to 4.24 mg of bisoprolol) and 5 mg of perindopril arginine (equivalent to 3.395 mg of perindopril).
• Other components are:
  In the tablet core: calcium chloride dihydrate, sodium carbonate, microcrystalline cellulose, lactose monohydrate, maize starch, colloidal anhydrous silica, sodium croscarmellose, magnesium stearate.
  In the tablet coating: polydextrose, calcium carbonate, hypromellose, talc, triglycerides, yellow iron oxide E 172, red iron oxide E 172.
  See section 2 “Biprindo contains sodium and lactose”.

What Biprindo looks like and contents of the pack
Biprindo 5 mg + 5 mg, coated tablets
Orange, oval, biconvex coated tablets with a division line on one side.
On one side of the division line, the tablet is marked with the letter B, and on the other side with the number 1.
Tablet dimensions: approximately 8 mm × 5 mm. The tablet can be divided into equal doses.
Biprindo is available in packs containing:

• 10, 30, 50, 60, 90 or 100 tablets in blister packs, in a cardboard carton.
• 7, 28, 56 or 98 tablets in calendar blister packs, in a cardboard carton.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

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

For more detailed information about this medicinal product, please contact the local representative of the marketing authorization holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5 Street
02-235 Warsaw
Tel. +48 22 57 37 500