Biprindo

Package leaflet: Information for the patient

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are identical.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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 more efficient at pumping blood throughout the body.
• Perindopril arginine is an angiotensin-converting enzyme (ACE) inhibitor. It works by widening blood vessels, which helps the heart pump blood more easily.

Biprindo is used to treat high blood pressure (hypertension) 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 supply 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, facial, tongue or throat swelling, severe itching or severe skin rash, or if such symptoms occurred in the patient or a blood relative under any circumstances (a condition called angioedema);
• if the patient is more than 3 months pregnant (it is also better 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 blood filtration by another method. Depending on the device used, Biprindo may not be suitable for the patient.
• if the patient has kidney disorders which reduce 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 "Biprindo with other medicines").

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

• if the patient has diabetes;
• if the patient has kidney problems (including patients after kidney transplantation) or is undergoing dialysis;
• if the patient has liver problems;
• if the patient has been diagnosed with aortic or mitral valve stenosis, hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the artery supplying blood to the kidney);
• if the patient has abnormally increased levels of a hormone called aldosterone in the blood (primary hyperaldosteronism);
• if the patient has heart failure or any other heart disease, 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 (high potassium levels in the blood may cause changes in heart rate);
• if the patient has recently had diarrhoea or vomiting, or is dehydrated (Biprindo may cause low 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 experiences 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,
the patient should stop taking Biprindo and contact a doctor immediately.

• in black patients, there is an increased 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 - for example, 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 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 called mTOR inhibitors (used to prevent rejection of transplanted organs and in cancer treatment);
• sacubitril (available in a combination medicine containing sacubitril and valsartan), used to treat chronic heart failure;
• linagliptin, saxagliptin, sitagliptin, vildagliptin and other medicines belonging to the group of drugs called gliptins (used to treat diabetes).

Do not suddenly stop taking Biprindo, as this may cause a severe
worsening of heart function. Treatment should not be stopped suddenly, 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 children and adolescents under 18 years of age.
Biprindo with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, and about any medicines the patient plans to take.
The effect of Biprindo may be influenced by other medicines, or Biprindo 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 adverse effects.
Tell the 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 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 clotting;

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 of drugs called mTOR inhibitors). See section "Warnings and precautions".
• a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See sections "When not to use 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 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 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 is planning to have
a child, she should consult a 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 stopping Biprindo before pregnancy or as soon as the patient learns she is pregnant, 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 starts breastfeeding. Biprindo is not recommended for mothers who are breastfeeding, and the doctor may choose another treatment method if the patient wishes to breastfeed, especially if the child is a newborn or was born prematurely.
Driving and using machines
Biprindo usually does not affect alertness, but in some patients dizziness or weakness related to low blood pressure may occur, especially at the beginning of treatment or after a change in medication or in combination with alcohol. In such a case, the ability to drive and 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 a doctor before taking the medicine.
3. How to take Biprindo
This medicine should always be used 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, in the morning before a meal.
Kidney function disorders
Biprindo is not recommended for patients with moderate or severe kidney disease.
Use in children and adolescents
Use is not recommended in children and adolescents.
Taking more than the recommended dose of Biprindo
If too many tablets are taken, contact a doctor or pharmacist immediately.
The most likely symptoms of overdose are low blood pressure, which may cause dizziness or fainting (if this occurs, placing the patient with legs elevated may help), severe breathing difficulties, tremor (due to low blood sugar levels) and slowed heart rate.
Missing a dose of Biprindo
It is important to take the medicine regularly every day, as this improves its effectiveness. However, if a dose of Biprindo is missed, the next dose should be taken 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 stop treatment suddenly, especially in patients with coronary artery disease.
If there are any further doubts regarding the use of this medicine, consult a 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 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 very poor general condition (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 starting 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 adverse reaction 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 dizziness;
• labyrinthine dizziness;
• taste disturbances;
• tingling;
• numbness of hands or feet;
• visual disturbances;
• tinnitus (sensation of hearing sounds);
• feeling 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;
• increased 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 oedema;
• fever;
• falls;
• changes in laboratory test results: high potassium levels in blood, transient and resolving after discontinuation of treatment, low sodium levels, hypoglycaemia (very low blood sugar levels) in patients with diabetes, 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;
• allergic-type reactions: itching, hot flushes, rash;
• exacerbation of psoriasis;
• changes in laboratory test results: increased liver enzyme activity, high bilirubin levels in serum, 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;
• occurrence or worsening of psoriasis, psoriasiform rash;
• blood count changes such as decreased numbers of white and red blood cells, decreased haemoglobin levels, decreased platelet count.

Frequency not known (cannot be estimated from 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 adverse reactions not listed in this leaflet, you should inform your doctor or pharmacist. 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
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 provide more information on the safety of the medicine.

5. How to store the medicine Biprindo

Keep the 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 expiry date refers to the last day of the stated month.
Store in the original packaging to protect from moisture.
No special temperature storage instructions for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer in use. This will help protect the
environment.

6. Contents of the packaging and other information

What Biprindo contains

• The active substances in this medicine are bisoprolol fumarate and perindopril arginine. Each tablet 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).
• Other ingredients are:
  In the tablet core: calcium chloride hexahydrate, sodium carbonate, microcrystalline cellulose, lactose monohydrate, pregelatinized starch (corn), colloidal anhydrous silica, sodium croscarmellose, magnesium stearate.
  In the tablet coating: polydextrose, calcium carbonate, hypromellose, talc, triglycerides.
  See section 2 "Biprindo contains sodium and lactose".

What Biprindo looks like and contents of the pack
Biprindo 10 mg + 10 mg, coated tablets
White or almost white, oval, biconvex coated tablets, with a score line on one side. On one side of the score line, the tablet is marked with the letter B, and on the other side with the number 4. Tablet dimensions: approximately 12 mm × 6 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 box.
• 7, 28, 56 or 98 tablets in calendar blister packs, in a cardboard box.

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 Street 5
02-235 Warsaw
Tel. 22 57 37 500