Biprindo

Package leaflet: Information for the patient

Biprindo, 10 mg + 5 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, 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. 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 or pharmacist. See section 4.

Leaflet 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 slow down the 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 dilating blood vessels, which helps the heart pump blood more easily.

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, resulting in breathlessness and swelling), and (or) to reduce the risk of cardiovascular events such as myocardial infarction 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 myocardial infarction 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 serious heart condition caused by 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 the patient or a 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 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 another method of blood filtration. 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, because the risk of angioedema (rapid swelling of tissues under the skin around the throat) is increased (see "Warnings and precautions" and "Biprindo with other medicines").

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

• if the patient has diabetes;
• if the patient has kidney problems (this also applies to patients who have had a kidney transplant) or if the patient is undergoing dialysis;
• if the patient has liver problems;
• 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 (a 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 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 due 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 due to undergo anaesthesia and (or) surgery;
• if the patient has circulation problems in the limbs;
• if the patient has asthma or chronic lung disease;
• if the patient has (or has had) psoriasis;
• if the patient has a tumour of the adrenal gland (phaeochromocytoma);
• if the patient has thyroid disorders (Biprindo may mask symptoms of hyperthyroidism);
• if the patient has angioedema (a serious 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 developing 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 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 a 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 a group of drugs called gliptins (used to treat diabetes).

Do not stop taking Biprindo suddenly, as this may cause a serious 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. Biprindo 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 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 effects 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, 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 blood clots;
trimethoprim and cotrimoxazole, 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".
• 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); anaesthetic medicines 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 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 become pregnant, she should consult her 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 Biprindo before becoming pregnant or as soon as pregnancy is confirmed, and will recommend another medicine instead of Biprindo. Biprindo 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 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, after a change in medication, or when combined 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 a doctor before taking this 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.
Kidney function disorders
Biprindo is not recommended for patients with moderate or severe kidney disease.
Use in children and adolescents
Not recommended for use in children and adolescents.
Taking more Biprindo than recommended
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, 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 stop taking Biprindo suddenly or change the dose without consulting a doctor, as this may cause a significant worsening of heart function. Do not stop treatment abruptly, especially in patients with coronary artery disease.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will get them.
You should 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);
• pancreatitis, 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).

Medicine Biprindo is generally well tolerated, but as with other medicines, adverse reactions may occur in patients, 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;
• intensified 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 disorders);
• 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 after discontinuation of treatment, low sodium levels, hypoglycaemia (very low blood sugar levels) in diabetic patients, increased blood urea levels, increased creatinine levels in blood.

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

• acute kidney failure;
• dark urine, nausea or vomiting, muscle cramps, disorientation and seizures. These may be symptoms of a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion);
• reduced or absence of urine output;
• sudden redness of the face and neck;
• nightmares, hallucinations;
• decreased tear production (dry eyes);
• hearing problems;
• hepatitis, possibly causing 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 bilirubin levels in serum, abnormal blood lipid levels.

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

• disorientation;
• irritation and redness of the eyes (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 reduced number of white and red blood cells, reduced haemoglobin concentration, 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 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 authorisation holder.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store the medicine Biprindo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following the word
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 requirements 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 5 mg of perindopril arginine (equivalent to 3.395 mg of perindopril).
• The other ingredients are: In the tablet core: calcium chloride dihydrate, sodium carbonate, microcrystalline cellulose, lactose monohydrate, pregelatinized corn starch, colloidal anhydrous silica, sodium croscarmellose and magnesium stearate. In the tablet coating: polydextrose, calcium carbonate, hypromellose, talc, triglycerides, yellow iron oxide E 172. See section 2 "Biprindo contains sodium and lactose".

What Biprindo looks like and contents of the pack
Biprindo 10 mg + 5 mg, coated tablets
Yellow, oval, biconvex coated tablets with the marking "B2" on one side.
Tablet dimensions: approximately 12 mm × 6 mm.
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 Member States of the European Economic Area 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
Phone: +48 22 57 37 500