Piramil Biso

Leaflet attached to the packaging: patient information

Piramil Biso, 2.5 mg + 1.25 mg, hard capsules
Piramil Biso, 2.5 mg + 2.5 mg, hard capsules
Piramil Biso, 5 mg + 2.5 mg, hard capsules

Piramil Biso, 5 mg + 5 mg, hard capsules

Piramil Biso, 10 mg + 5 mg, hard capsules

Piramil Biso, 10 mg + 10 mg, hard capsules

Ramipril+ Bisoprolol fumarate
:

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

You should keep this leaflet, so you can read it again if you need to.
In case of any doubts, you should consult a doctor, pharmacist, or nurse.
This medicine has been prescribed specifically for you. Do not pass it on to others.
The medicine may harm another person, even if their symptoms are the same.
If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. What is Piramil Biso and what is it used for

Piramil Biso contains two active substances, bisoprolol fumarate and ramipril, in one capsule:
Ramipril is an angiotensin-converting enzyme inhibitor (ACEI). It works by dilating blood vessels, making it easier for the heart to pump blood.
Bisoprolol fumarate belongs to a group of medicines called beta-blockers. Beta-blockers slow down the heart rate and make the heart pump blood more efficiently.
Piramil Biso is used to treat high blood pressure (hypertension) and/or chronic heart failure with left ventricular dysfunction (a condition in which the heart is not able to pump enough blood to meet the body's needs, resulting in shortness of breath and swelling) and/or to reduce the risk of heart events, such as heart attack, in patients with chronic coronary artery disease (a condition in which the blood supply to the heart is reduced or blocked) who have had a heart attack and/or have undergone surgical procedures to improve blood flow to the heart, or with diabetes with at least one cardiovascular risk factor.
Instead of taking bisoprolol fumarate and ramipril in separate capsules, the patient takes only one capsule of Piramil Biso, which contains both active substances in the same amounts.

2. Important information before taking Piramil Biso

When not to take Piramil Biso

• if the patient is allergic to bisoprolol or any other beta-blocker, to ramipril 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 that has suddenly worsened and requires hospital treatment;
• if the patient has cardiogenic shock (a severe condition of the heart caused by very low blood pressure);
• if the patient has a heart condition characterized by slow or irregular heart rhythm (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 obstructive pulmonary disease;
• if the patient has severe circulatory disorders in the limbs (such as Raynaud's syndrome) that may cause tingling or blanching or cyanosis of the fingers and toes;
• if the patient has an untreated pheochromocytoma, a rare tumor of the adrenal gland;
• if the patient has metabolic acidosis, a condition in which the blood contains too many acids;
• if the patient has experienced symptoms such as wheezing, swelling of the face, tongue, or throat, intense itching, or severe skin rash during previous treatment with an ACE inhibitor, or if such symptoms have occurred in a relative under any other circumstances (a condition called angioedema);
• if the patient is pregnant for more than 3 months (it is also recommended to avoid taking Piramil Biso in early pregnancy - see "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, Piramil Biso may not be suitable for the patient.
• if the patient has kidney problems that reduce blood flow to the kidneys (renal artery stenosis);
• if the patient is being treated with a combination medicine containing sacubitril and valsartan, used to treat chronic heart failure (see "Warnings and precautions" and "Piramil Biso and other medicines").

Warnings and precautions

Before starting treatment with Piramil Biso, the patient should discuss it with their doctor or pharmacist if:

• the patient has diabetes;
• the patient has kidney problems (including patients who have had a kidney transplant) or is undergoing dialysis;
• the patient has liver disease;
• the patient has a narrowing of the aortic or mitral valve and hypertrophic cardiomyopathy or renal artery stenosis (narrowing of the arteries that supply blood to the kidneys);
• the patient has abnormally high levels of a hormone called aldosterone in the blood (primary aldosteronism);
• the patient has heart failure or any other heart condition, such as arrhythmias or severe chest pain at rest (Prinzmetal's angina);
• the patient has collagenosis (a disease of the connective tissue), such as systemic lupus erythematosus or scleroderma;
• the patient is on a low-salt diet or uses salt substitutes that contain potassium (high levels of potassium in the blood can cause changes in heart rhythm);
• the patient has recently had diarrhea or vomiting, or is dehydrated (Piramil Biso may cause a drop in blood pressure);
• the patient is undergoing LDL apheresis (removal of cholesterol from the blood using a special device);
• the patient is undergoing desensitization treatment to reduce allergic reactions to

bee or wasp stings;

• the patient is fasting or on a diet;
• the patient is undergoing anesthesia and/or surgery;
• the patient has circulatory disorders in the limbs;
• the patient has asthma or chronic obstructive pulmonary disease;
• the patient has (or has had) psoriasis;
• the patient has an adrenal gland tumor (pheochromocytoma);
• the patient has thyroid disorders (Piramil Biso may mask symptoms of hyperthyroidism);
• angioedema (a severe allergic reaction characterized by swelling of the face, lips, tongue, or throat, difficulty swallowing or breathing). This reaction can occur at any time during treatment. If the patient experiences such symptoms, they should stop taking Piramil Biso and contact their doctor immediately.
• the patient is of black African descent, as there is a higher risk of angioedema, and this medicine may be less effective in lowering blood pressure than in patients of other races.
• the patient is taking any of the following medicines used to treat high blood pressure:
• angiotensin receptor blockers (ARBs) (also known as sartans - e.g., valsartan, telmisartan, irbesartan), especially if the patient has diabetic kidney disease;
• aliskiren. The doctor may monitor kidney function, blood pressure, and electrolyte levels (e.g., potassium) at regular intervals. See also the information in the "When not to take Piramil Biso" and "Warnings and precautions" sections.
• the patient is taking any of the following medicines, which increase the risk of angioedema:
• racecadotril (used to treat diarrhea);
• sirolimus, everolimus, temsirolimus, and other medicines belonging to the group of medicines called mTOR inhibitors (used to prevent organ rejection);
• sacubitril (available in a combination medicine containing sacubitril and valsartan), used to treat chronic heart failure.

Do not stop taking Piramil Biso suddenly, as this may cause severe worsening of heart function. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease.
The patient should tell their doctor if they think they may be pregnant. Piramil Biso is not recommended in early pregnancy and should not be taken if the patient is pregnant for more than 3 months, as the medicine may cause serious harm to the baby if taken after the third month of pregnancy.
Pregnancy
The patient should tell their doctor if they are pregnant or think they may be pregnant. Usually, the doctor will advise stopping Piramil Biso before becoming pregnant or as soon as the patient knows they are pregnant and will prescribe a different medicine instead of Piramil Biso. Piramil Biso is not recommended in early pregnancy and should not be taken if the patient is pregnant for more than 3 months, as the medicine may cause serious harm to the baby if taken after the third month of pregnancy.
Breast-feeding
The patient should tell their doctor if they are breast-feeding or plan to breast-feed. Piramil Biso is not recommended for breast-feeding women. The doctor may choose a different treatment if the patient wants to breast-feed, especially if the baby is a newborn or was born prematurely.

Driving and using machines

Piramil Biso usually does not affect alertness, but some patients may experience dizziness or weakness due to low blood pressure, especially at the beginning of treatment or when changing the medicine or in combination with alcohol. In such cases, the ability to drive and operate machines may be impaired.
Lactose
Piramil Biso, 2.5 mg + 1.25 mg, contains 40.97 mg of lactose (20.49 mg of glucose and 20.49 mg of galactose) per dose. This should be taken into account in patients with diabetes.
Piramil Biso, 2.5 mg + 2.5 mg, contains 40.97 mg of lactose (20.49 mg of glucose and 20.49 mg of galactose) per dose. This should be taken into account in patients with diabetes.
Piramil Biso, 5 mg + 2.5 mg, contains 81.94 mg of lactose (40.97 mg of glucose and 40.97 mg of galactose) per dose. This should be taken into account in patients with diabetes.
Piramil Biso, 5 mg + 5 mg, contains 81.94 mg of lactose (40.97 mg of glucose and 40.97 mg of galactose) per dose. This should be taken into account in patients with diabetes.
Piramil Biso, 10 mg + 5 mg, contains 163.88 mg of lactose (81.94 mg of glucose and 81.94 mg of galactose) per dose. This should be taken into account in patients with diabetes.
Piramil Biso, 10 mg + 10 mg, contains 163.88 mg of lactose (81.94 mg of glucose and 81.94 mg of galactose) per dose. This should be taken into account in patients with diabetes.
Sodium
Piramil Biso contains less than 1 mmol of sodium (23 mg) per capsule, which means the medicine is considered "sodium-free".

3. How to take Piramil Biso

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. In case of doubt, the patient should consult their doctor or pharmacist.
The recommended dose is one capsule once a day. The capsule should be swallowed with a glass of water, in the morning before breakfast.
Patients with kidney disease
In patients with moderate kidney disease, the doctor will adjust the dose of Piramil Biso. Piramil Biso is not recommended for patients with severe kidney disease.
Patients with liver disorders
The doctor will closely monitor patients with mild or moderate liver disease when starting treatment with Piramil Biso.

Use in children and adolescents

Piramil Biso is not recommended for use in children and adolescents under 18 years of age.

Overdose of Piramil Biso

In case of taking more capsules than prescribed, the patient should contact their doctor or pharmacist immediately.
The most likely symptom of overdose is low blood pressure, which can cause dizziness or fainting (if this happens, it can be helped by laying the patient down with their legs raised), severe breathing difficulties, tremors (due to low blood sugar), and slow heart rate.

Missed dose of Piramil Biso

It is important to take the medicine regularly, every day, as its effect is better. However, if a dose of Piramil Biso is missed, the next dose should be taken at the usual time. A double dose should not be taken to make up for a missed dose.

Stopping treatment with Piramil Biso

Do not stop taking Piramil Biso suddenly or change the dose without consulting the doctor, as this may cause significant worsening of heart function. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease.
In case of any further doubts about taking this medicine, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Piramil Biso can cause side effects, although not everybody gets them.

The patient should stop taking this medicine and contact their doctor immediately if they experience any of the following side effects:

• severe dizziness or fainting due to low blood pressure (common - occurs in less than 1 in 10 people);
• worsening of heart failure causing severe shortness of breath and/or fluid retention (common - occurs in less than 1 in 10 people);
• swelling of the face, lips, mouth, tongue, or throat, difficulty breathing (angioedema; uncommon - occurs in less than 1 in 100 people);
• sudden onset of wheezing, chest pain, shortness of breath, or difficulty breathing (bronchospasm; uncommon - occurs in less than 1 in 100 people);
• very fast or irregular heartbeat, chest pain (angina pectoris), or heart attack (very rare - occurs in less than 1 in 10,000 people);
• weakness of arm or leg muscles, or difficulty speaking, which may be a sign of a stroke (very rare - occurs in less than 1 in 10,000 people);
• pancreatitis, which can cause severe abdominal pain and very poor general condition (very rare - occurs in less than 1 in 10,000 people);
• yellowing of the skin or eyes (jaundice), which can be a sign of liver inflammation (very rare - occurs in less than 1 in 10,000 people);
• rash often starting with red, itchy patches on the face, arms, or legs (erythema multiforme; very rare - occurs in less than 1 in 10,000 people).

Piramil Biso is usually well tolerated, but like other medicines, it can cause side effects, especially at the beginning of treatment.

The patient should tell their doctor or pharmacist immediately if they experience any of the following side effects:

very common (occurs in more than 1 in 10 people):

• slow heart rate;

common (occurs in less than 1 in 10 people):

• headache;
• dizziness of central origin;
• fainting, abnormally low blood pressure, especially when standing up or changing position quickly;
• numbness of hands or feet;
• feeling of cold hands or feet;
• cough;
• shortness of breath;
• sinusitis or bronchitis;
• chest pain;
• gastrointestinal disorders, such as nausea, vomiting, abdominal pain, indigestion, or difficulty digesting food, diarrhea, constipation;
• allergic reactions, such as rash, itching;
• muscle cramps, muscle pain;
• feeling of weakness;
• fatigue;
• higher than normal levels of potassium in blood test results.

uncommon (occurs in less than 1 in 100 people):

• dizziness of peripheral origin;
• disturbances of taste;
• tingling sensation (paresthesia);
• vision disturbances;
• ringing in the ears (tinnitus);
• nasal congestion, difficulty breathing;
• common cold, nasal congestion;
• hot flushes;
• mood changes;
• sleep disturbances;
• depression;
• dry mouth;
• sweating;
• kidney problems;
• passing more urine than usual during the day;
• impotence;
• increased levels of a type of white blood cell (eosinophils);
• drowsiness;
• palpitations;
• rapid heartbeat;
• irregular heartbeat (conduction disorders);
• muscle weakness;
• joint pain;
• peripheral edema;
• fever;
• loss of appetite (anorexia);
• changes in laboratory test results: increased levels of a type of white blood cell (eosinophilia), increased levels of urea in the blood, increased levels of creatinine in the blood, increased activity of liver enzymes, high levels of bilirubin in the blood;
• increased levels of protein in the urine;
• mouth ulcers;
• breast enlargement in men.

rare (occurs in less than 1 in 1,000 people):

• nightmares, hallucinations;
• reduced tear secretion (dry eyes);
• redness, itching, or tearing of the eyes;
• hearing disturbances;
• liver inflammation, which can cause yellowing of the skin or eyes;
• inflammation of blood vessels;
• changes in laboratory test results: changes in fat levels, increased levels of red or white blood cells or platelets, or changes in hemoglobin levels.

very rare (occurs in less than 1 in 10,000 people):

• confusion;
• pancreatitis (which can cause severe abdominal pain and very poor general condition);
• hair loss;
• onset or worsening of psoriasis, psoriasis-like rash;
• increased sensitivity of the skin to sunlight (photoreactions)

frequency not known (frequency cannot be estimated from the available data):

• change in color, feeling of numbness, and pain in the fingers and toes (Raynaud's phenomenon);
• low levels of sodium, very low levels of sugar (hypoglycemia) in patients with diabetes;
• inflammation of the tongue.

Concentration of urine (dark urine color), nausea, or vomiting, muscle cramps, confusion, and convulsions, which may be caused by inappropriate secretion of antidiuretic hormone, may occur with the use of ACE inhibitors. If such symptoms occur, the patient should contact their doctor as soon as possible.

Reporting side effects

If the patient experiences any side effects, including any possible side effects not listed in the leaflet, they should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Piramil Biso

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after 'EXP'.
The expiry date refers to the last day of the month.
Do not store the medicine at temperatures above 30°C. Do not store in the refrigerator or freeze.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Piramil Biso contains

The active substances of Piramil Biso are ramipril and bisoprolol fumarate.
The other ingredients are:
Contents of the capsule: lactose monohydrate, polyvinyl alcohol, sodium croscarmellose, sodium stearyl fumarate, microcrystalline cellulose, calcium hydrogen phosphate anhydrous, crospovidone type A, colloidal silicon dioxide anhydrous, magnesium stearate.
AquaPolish P yellow coating: hypromellose, hydroxypropyl cellulose, medium-chain triglycerides, talc, titanium dioxide (E 171), yellow iron oxide (E 172).

Capsule shell:titanium dioxide (E 171), gelatin, red iron oxide (E 172) - [capsules of 10 mg+10 mg, 10 mg+5 mg, 5 mg+5 mg, 5 mg+2.5 mg], yellow iron oxide (E 172) - [capsules of 10 mg+5 mg, 5 mg+5 mg, 5 mg+2.5 mg, 2.5 mg + 2.5 mg, 2.5 mg + 1.25 mg], quinoline yellow (E 104) - [capsules of 5 mg+2.5 mg, 2.5 mg + 2.5 mg, 2.5 mg + 1.25 mg].
Ink:shellac, black iron oxide (E 172), propylene glycol, concentrated ammonia solution, potassium hydroxide.

What Piramil Biso looks like and contents of the pack

Piramil Biso, 2.5 mg + 1.25 mg, hard capsules
The capsule has a yellow cap with black printing "2.5 mg" and a white body with black printing "1.25 mg".
Contents of the capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet.
Piramil Biso, 2.5 mg + 2.5 mg, hard capsules
The capsule has a yellow cap with black printing "2.5 mg" and a yellow body with black printing "2.5 mg".
Contents of the capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet.
Piramil Biso, 5 mg + 2.5 mg, hard capsules
The capsule has an orange cap with black printing "5 mg" and a yellow body with black printing "2.5 mg".
Contents of the capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet.
Piramil Biso, 5 mg + 5 mg, hard capsules
The capsule has an orange cap with black printing "5 mg" and an orange body with black printing "5 mg".
Contents of the capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet.
Piramil Biso, 10 mg + 5 mg, hard capsules
The capsule has a reddish-brown cap with black printing "10 mg" and an orange body with black printing "5 mg".
Contents of the capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of one yellow, biconvex, film-coated, round tablet.
Piramil Biso, 10 mg + 10 mg, hard capsules
The capsule has a reddish-brown cap with black printing "10 mg" and a reddish-brown body with black printing "10 mg".
Contents of the capsule: ramipril in the form of a white or almost white powder and bisoprolol fumarate in the form of two yellow, biconvex, film-coated, round tablets.
Blisters of BOPA/Aluminum/PVC/Aluminum
The blisters and leaflet are placed in a carton.
The capsules are available in packs of 10, 30, 60, or 100 capsules.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl, Austria
Manufacturer:
Adamed Pharma S.A.
Marszałka Józefa Piłsudskiego 5
95-200 Pabianice, Poland
Lek Pharmaceuticals d.d.
Verovškova 57
1526 Ljubljana, Slovenia

This medicine is authorized in the Member States of the European Economic Area under the following names:

Poland
Piramil Biso
Germany
Ramipril HEXAL plus Bisoprolol 2.5 mg/1.25 mg Hartkapseln
Ramipril HEXAL plus Bisoprolol 2.5 mg/2.5 mg Hartkapseln
Ramipril HEXAL plus Bisoprolol 5 mg/2.5 mg Hartkapseln
Ramipril HEXAL plus Bisoprolol 5 mg/5 mg Hartkapseln
Ramipril HEXAL plus Bisoprolol 10 mg/5 mg Hartkapseln
Ramipril HEXAL plus Bisoprolol 10 mg/10 mg Hartkapseln
Italy
Ramilolo

For more information about this medicine, the patient should contact their local representative of the marketing authorization holder:

Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00
Date of last revision of the leaflet:11/2023
Sandoz logo