Piramil Biso

Leaflet accompanying 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 that 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 to the whole body.
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 heart's blood supply is reduced or blocked) who have had a heart attack and/or have undergone a surgical procedure to improve blood flow to the heart by widening the blood vessels that supply it, or 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, ramipril or any other ACE inhibitor, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has heart failure that is worsening rapidly 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 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 discoloration 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, lips, tongue, or throat, intense itching, or severe skin rash during previous treatment with an ACE inhibitor;
• if the patient is pregnant for more than 3 months (it is also recommended to avoid taking Piramil Biso during 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/or hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the arteries that supply the kidneys with blood);
• the patient has an abnormally high level of a hormone called aldosterone in the blood (primary aldosteronism);
• the patient has heart failure or any other heart disease, such as arrhythmias or severe chest pain at rest (Prinzmetal's angina);
• the patient has a collagen disease, 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 can cause a drop in blood pressure);
• the patient is undergoing LDL apheresis (a procedure to remove cholesterol from the blood using a special device);
• the patient is undergoing desensitization treatment to reduce allergic reactions to bee or wasp stings;

and

• 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 the 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) in the blood 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 the rejection of transplanted organs);
• 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 can 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 are (or may be) pregnant. Piramil Biso is not recommended during 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 during this period (see "Pregnancy").

Children and adolescents

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

Piramil Biso and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. Other medicines may affect the action of Piramil Biso or Piramil Biso may affect the action of other medicines. This type of interaction can cause one or both medicines to be less effective. It can also increase the risk or severity of side effects.
The patient should tell their doctor if they are taking any of the following medicines:

• medicines used to regulate blood pressure or heart disease (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 receptor blockers (ARBs), aliskiren (see also the information in the "When not to take Piramil Biso" and "Warnings and precautions" sections), or diuretics (medicines that increase the amount of urine produced 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 and cotrimoxazole, also known as a combination medicine containing trimethoprim and sulfamethoxazole);
• potassium-sparing medicines used to treat heart failure: eplerenone and spironolactone in doses of 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 used to treat diarrhea (racecadotril) or to prevent the rejection of transplanted organs (sirolimus, everolimus, temsirolimus, and other medicines belonging to the group of medicines called mTOR inhibitors). See the "Warnings and precautions" section.
• a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure). See the "When not to take Piramil Biso" and "Warnings and precautions" sections.
• lithium used to treat mania or depression;
• certain medicines used to treat depression, such as imipramine, amitriptyline, monoamine oxidase inhibitors (MAOIs; except MAO-B inhibitors);
• certain medicines used to treat schizophrenia (antipsychotic medicines);
• certain medicines used to treat epilepsy (phenytoin, barbiturates, such as phenobarbital);
• anesthetics used in surgical procedures;
• vasodilators, including nitrates (medicines that cause blood vessels to widen);
• trimethoprim used to treat infections;
• immunosuppressants (medicines that reduce the body's immune response), such as cyclosporine, tacrolimus, used to treat autoimmune disorders or after organ transplantation;
• allopurinol used to treat gout;
• parasympathomimetic medicines used to treat diseases such as Alzheimer's disease or glaucoma;
• topical beta-blockers used to treat glaucoma (increased pressure in the eye);
• mefloquine used to prevent or treat malaria;
• baclofen used to treat muscle stiffness in diseases such as multiple sclerosis;
• gold salts, especially when given 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 medicines (NSAIDs), such as ibuprofen, diclofenac, or high doses of acetylsalicylic acid, used to treat arthritis, headache, pain, or inflammation.

Piramil Biso with food, drink, and alcohol

Piramil Biso should be taken before a meal.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.
Pregnancy
The patient should tell their doctor if they think they are (or may be) pregnant. Usually, the doctor will advise stopping Piramil Biso before becoming pregnant or as soon as the patient finds out they are pregnant and will prescribe a different medicine instead of Piramil Biso. Piramil Biso is not recommended during 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 during this period.
Breastfeeding
The patient should tell their doctor if they are breastfeeding or plan to breastfeed. Piramil Biso is not recommended for breastfeeding women. The doctor may choose a different treatment if the patient wants to breastfeed, 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 per day. The capsule should be swallowed with a glass of water, in the morning before a meal.
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 function 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.

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 a drop in 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 difficulty breathing, tremors (due to low blood sugar), and slow heart rate.

Missing a 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

The patient should not stop taking Piramil Biso suddenly or change the dose without consulting their doctor, as this can 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 rapid 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, radiating to the back, and very poor general condition (very rare - occurs in less than 1 in 10,000 people);
• jaundice (yellowing of the skin or eyes), which can be a sign of liver inflammation (very rare - occurs in less than 1 in 10,000 people);
• a 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, patients may experience various side effects, especially at the beginning of treatment.

The patient should inform 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;
• high levels of potassium in blood test results.

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

• dizziness of peripheral origin;
• taste disorders;
• tingling sensation (paresthesia);
• vision disorders;
• tinnitus (feeling of noise in the ears);
• nasal congestion, difficulty breathing, or worsening of asthma;
• common cold, nasal congestion;
• hot flashes;
• mood changes;
• sleep disorders;
• depression;
• dry mouth;
• sweating;
• kidney disease;
• increased urine production during the day;
• impotence;
• increased eosinophil count (a type of white blood cell);
• drowsiness;
• palpitations;
• tachycardia;
• irregular heart rhythm (atrioventricular conduction disorders);
• muscle weakness;
• joint pain;
• peripheral edema;
• fever;
• loss of appetite (anorexia);
• changes in laboratory test results: increased eosinophil count, increased urea levels in the blood, increased creatinine levels in the blood, increased liver enzyme activity, high bilirubin levels in the blood;
• increased protein levels in the urine;
• mouth ulcers;
• breast enlargement in men.

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

• nightmares, hallucinations;
• decreased tear production (dry eyes);
• redness, itching, or tearing of the eyes;
• hearing disorders;
• liver inflammation, which can cause yellowing of the skin or eyes;
• vasculitis;
• changes in laboratory test results: changes in lipid levels, increased red blood cell count, white blood cell count, or platelet count, or changes in hemoglobin levels.

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

• disorientation;
• pancreatitis (which can cause severe abdominal pain, radiating to the back);
• hair loss;
• onset or worsening of psoriasis, psoriasis-like rash;
• increased sensitivity of the skin to sunlight (phototoxic reactions)

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

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

Concentrated urine (dark urine color), nausea, or vomiting, muscle cramps, disorientation, and seizures, which can 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 Monitoring 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
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 stated.
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 anhydrous silica, 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
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