Bisoratio 5

Patient Information Leaflet

Bisoratio 5; 5 mg, tablets
Bisoprolol fumarate
Bisoratio 10; 10 mg, tablets
Bisoprolol fumarate
Please read all of this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Bisoratio is and what it is used for

The active substance in Bisoratio is bisoprolol fumarate. Bisoprolol belongs to a group of medicines called beta-blockers. These medicines affect the body's response to certain nerve impulses, especially in the heart. As a result, bisoprolol slows down heart activity and thereby improves the heart's efficiency in pumping blood throughout the body. Bisoprolol at doses of 5 mg and 10 mg lowers high blood pressure.

Bisoratio is used to treat:

• high blood pressure (hypertension);
• ischaemic heart disease (chest pain caused by inadequate oxygen supply to the heart);
• chronic stable heart failure of moderate to severe intensity with impaired systolic ventricular function (ejection fraction ≤35% as assessed by echocardiography), in combination with ACE inhibitors, diuretics, and - if necessary - cardiac glycosides.

2. Information before using Bisoratio

When not to use Bisoratio
Do not use Bisoratio in the following cases:

• if the patient is allergic to bisoprolol or any of the other ingredients of this medicine (listed in section 6);
• if the patient has severe bronchial asthma or severe chronic obstructive pulmonary disease (COPD);
• if the patient has serious circulatory disorders in the limbs (such as Raynaud's syndrome), which may cause tingling, paleness or blueness of fingers or toes;
• if the patient has untreated phaeochromocytoma, a rare tumour of the adrenal gland;
• if the patient has metabolic acidosis, a condition in which blood pH is abnormal;
• if the patient has acute heart failure;
• if the patient's heart failure worsens and intravenous administration of drugs increasing heart contractility is required;
• if the patient has symptoms of a slow heartbeat;
• if the patient has symptoms of low blood pressure;
• if the patient has certain heart diseases causing very slow or irregular heartbeat (second- or third-degree atrioventricular block, sinoatrial block, sick sinus syndrome) without a pacemaker;
• if the patient has cardiogenic shock, i.e. an acute, life-threatening impairment of heart function leading to low blood pressure and circulatory failure.

Warnings and precautions
If any of the following conditions apply, talk to your doctor before starting treatment with Bisoratio; the doctor may decide that special caution is required (e.g. additional medication or more frequent monitoring):

• diabetes;
• strict fasting;
• certain heart diseases (such as heart rhythm disorders or severe chest pain at rest – Prinzmetal's angina);
• mild circulatory disorders in the limbs;
• mild bronchial asthma or chronic lung disease;
• presence of scaly skin lesions (psoriasis), even in medical history;
• thyroid function disorders;
• phaeochromocytoma of the adrenal medulla;
• first-degree atrioventricular block.

Additionally, inform your doctor if you are planning:

• allergen immunotherapy (e.g. to prevent hay fever), as Bisoratio may increase the likelihood of an allergic reaction or intensify such a reaction;
• surgery under general anaesthesia, as Bisoratio may alter the body's response to anaesthetic drugs.

Treatment of chronic stable heart failure with bisoprolol must be initiated with a dose-titration phase.
Starting and stopping treatment for chronic stable heart failure with bisoprolol requires regular monitoring.
There is insufficient experience with the use of bisoprolol in patients with heart failure and concomitant diseases/conditions such as:

• NYHA class II heart failure;
• insulin-dependent (type I) diabetes;
• severe renal impairment (serum creatinine concentration ≥300 µmol/l or ≥3.4 mg/dl);
• severe hepatic impairment;
• patients over 80 years of age;
• restrictive cardiomyopathy;
• congenital heart defects;
• hemodynamically significant valvular heart disease;
• myocardial infarction within the last 3 months.

During bisoprolol treatment, the doctor should recommend appropriate tests to monitor cardiovascular function, especially in elderly patients.
Bisoprolol treatment should not be stopped abruptly, particularly in patients with ischaemic heart disease. Abrupt discontinuation of treatment in patients with ischaemic heart disease is associated with an increased risk of myocardial infarction and sudden death. In patients with severe ischaemic heart disease, the benefit-risk ratio of bisoprolol treatment should be critically evaluated.

Children and adolescents
Bisoratio is not recommended for use in children and adolescents.

Bisoratio and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Do not take the following medicines together with Bisoratio without specific medical advice:

• certain medicines used to treat high blood pressure, coronary heart disease or heart rhythm disorders (calcium channel blockers such as verapamil and diltiazem);
• certain medicines used to treat high blood pressure, such as clonidine, methyldopa, moxonidine, rilmenidine. However, do not stop taking these medicines without consulting your doctor;
• certain medicines used to treat high blood pressure or coronary heart disease (dihydropyridine-type calcium channel blockers such as felodipine and amlodipine);
• certain medicines used to treat heart rhythm disorders (class I antiarrhythmics such as quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone);
• certain medicines used to treat heart rhythm disorders (class III antiarrhythmics such as amiodarone);
• locally applied beta-blockers (e.g. eye drops used to treat glaucoma);
• certain medicines used to treat, for example, Alzheimer's disease or glaucoma (parasympathomimetics);
• medicines used to treat acute heart disorders (adrenergic agonists such as isoprenaline and dobutamine);
• insulin and oral antidiabetic medicines;
• agents used in general anaesthesia (e.g. during surgery);
• digitalis glycosides used to treat heart failure;
• non-steroidal anti-inflammatory drugs (NSAIDs) used to treat joint inflammation, relieve pain and inflammation (e.g. ibuprofen and diclofenac);
• adrenaline, used to treat severe, life-threatening allergic reactions and in cardiac arrest;
• any medicines that may lower blood pressure, either as a desired or undesirable effect, such as antihypertensive medicines, certain tricyclic antidepressants, certain antiepileptic medicines or those used during general anaesthesia (barbiturates), and certain medicines used in psychiatric disorders characterised by loss of contact with reality (phenothiazine derivatives);
• mefloquine, used for prevention and treatment of malaria;
• medicines used to treat depression, known as monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors);
• rifampicin, an antibiotic used to treat infections;
• ergotamine derivatives, medicines used to treat dementia and migraine headaches.

Bisoratio with food and drink
Tablets may be taken with food. Swallow them with a small amount of liquid. Do not chew.

Pregnancy and breastfeeding
There is a risk that using Bisoratio during pregnancy may harm the unborn child.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine. The doctor will decide whether Bisoratio can be used during pregnancy.
It is not known whether bisoprolol passes into human breast milk; therefore, breastfeeding is not recommended during treatment with Bisoratio.

Driving and using machines
Depending on individual response, this medicine may impair the ability to drive or operate machinery. Exercise particular caution at the beginning of treatment, after dose increases, or when changing medications, as well as when combining the medicine with alcohol.

Bisoratio contains lactose monohydrate.
Each Bisoratio 5 tablet contains 135.7 mg of lactose monohydrate.
Each Bisoratio 10 tablet contains 130.4 mg of lactose monohydrate.
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 use Bisoratio

This medicine should always be used exactly as directed by your doctor. If you are unsure, consult
your doctor or pharmacist.
Regular medical check-ups are necessary during treatment with Bisoratio. This is particularly
important at the beginning of treatment, when increasing the dose, and when discontinuing therapy.
Adults
For arterial hypertension and ischemic heart disease, the usual dose is one tablet of Bisoratio 5 or 1/2 tablet of Bisoratio 10 (equivalent to 5 mg of bisoprolol fumarate) once daily. If necessary, your doctor may increase the dose to one tablet of Bisoratio 10 mg or two tablets of Bisoratio 5 mg (corresponding to 10 mg of bisoprolol fumarate) once daily.
The maximum daily dose is 20 mg.
In all cases, the lowest effective dose should be used.
Liver or kidney function impairment
In patients with mild to moderate liver or kidney dysfunction, dose adjustment is usually not required. In patients with severe renal or hepatic impairment, doses exceeding 10 mg of bisoprolol per day should not be used.
Experience with bisoprolol in patients undergoing dialysis is limited; however, there is no evidence to suggest dose adjustment is necessary.
Elderly patients
Dose adjustment is not necessary. Treatment should be initiated at the lowest possible dose.
Use in children and adolescents
Bisoratio is not recommended for use in children and adolescents.
Duration of treatment
Treatment with Bisoratio is usually long-term.
Do not abruptly discontinue treatment with Bisoratio. If discontinuation is necessary, the dose should be gradually reduced by half every week.
Method of administration
Tablets should be taken every morning, on an empty stomach or with breakfast; do not chew; swallow with sufficient fluid.
Stable chronic heart failure of moderate to severe degree
This medicine is used in patients diagnosed with stable chronic heart failure who have not experienced acute decompensation within the last six weeks and whose treatment for the underlying condition has not been changed in the previous two weeks.
Before initiating bisoprolol therapy, patients should be treated with an optimal dose of an angiotensin-converting enzyme (ACE) inhibitor (or another vasodilator if ACE inhibitors are not tolerated), a diuretic, and, if necessary, a cardiac glycoside.
Recommendation:
The treating physician should have experience in managing chronic heart failure.
Dose titration phase
Treatment of stable chronic heart failure with bisoprolol requires a dose titration phase.
Treatment should be initiated at a low dose and gradually increased according to the schedule below. The doses required during the initial phase of treatment (1.25 mg, 3.75 mg) cannot be achieved using this medicinal product.

• 1.25 mg once daily for 1 week (other dosage forms are available for this dose). If this dose is well tolerated, increase to:
• 2.5 mg once daily for 1 week. If this dose is well tolerated, increase to:
• 3.75 mg once daily for 1 week (other dosage forms are available for this dose). If this dose is well tolerated, increase to:
• 5 mg once daily for 4 weeks. If this dose is well tolerated, increase to:
• 7.5 mg once daily for 4 weeks. If this dose is well tolerated, increase to:
• 10 mg once daily (maintenance dose). After the first administration of 1.25 mg, the patient should be observed for 4 hours; particular attention should be paid to blood pressure, heart rate, conduction disturbances, and signs of worsening heart failure.

The maximum recommended dose of bisoprolol is 10 mg once daily.
The occurrence of adverse reactions may prevent all patients from reaching the maximum recommended doses. If necessary, the achieved dose may be gradually reduced. Treatment may be interrupted and restarted if needed. If worsening of heart failure symptoms or signs of intolerance occur during the dose titration period, it is recommended to first reduce the bisoprolol dose or, if necessary, discontinue treatment (especially in cases of severe hypotension, worsening heart failure with acute pulmonary edema, cardiogenic shock, symptomatic bradycardia, or atrioventricular block).
Treatment of chronic compensated heart failure with bisoprolol is usually long-term.
Do not abruptly discontinue bisoprolol, as this may lead to transient worsening of heart failure. If discontinuation is necessary, the dose should be gradually reduced (e.g., reducing the dose by half every week).
Tablets should be taken in the morning. They may be taken with food. Swallow with a small amount of fluid, do not chew.
Liver and kidney dysfunction
There are no data on the pharmacokinetics of bisoprolol in patients with chronic heart failure and concomitant renal or hepatic impairment. Dose selection in these patients should be done with particular caution.
Elderly patients
Dose adjustment is not necessary.
Use in children and adolescents
There is a lack of clinical data on the use of this medicine in this age group; therefore, its use is not recommended.
Taking more Bisoratio than recommended
If you take more Bisoratio than prescribed, contact your doctor immediately. The doctor will decide on the necessary actions. Symptoms of overdose may include: slowed heart rate, difficulty breathing, significant drop in blood pressure, dizziness, or seizures (caused by low blood sugar).
Missed dose of Bisoratio
Do not take a double dose to make up for a missed dose. Take the next scheduled dose as usual the following morning.
Stopping Bisoratio treatment
Never stop taking Bisoratio unless instructed by your doctor. Otherwise, your condition may worsen.
Do not abruptly stop taking bisoprolol, as this may lead to transient worsening of heart failure. If discontinuation is necessary, the dose should be gradually reduced (e.g., reducing the dose by half every week).
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Very common (affecting more than 1 in 10 people):

• bradycardia (in patients with chronic heart failure).

Common (affecting less than 1 in 10 people):

• fatigue*, dizziness*, headache*;
• sensation of coldness or numbness in hands or feet;
• hypotension, especially in patients with heart failure;
• gastrointestinal disturbances such as nausea, vomiting, diarrhoea, constipation;
• worsening of existing heart failure (in patients with chronic heart failure).

* These symptoms occur mainly at the beginning of treatment. They are usually mild and resolve within 1–2 weeks.
Uncommon (affecting less than 1 in 100 people):

• atrioventricular conduction disturbances, worsening of existing heart failure, bradycardia (slow heart rate);
• sleep disturbances;
• depression;
• asthenia (weakness);
• bronchospasm (difficulty breathing) in patients with bronchial asthma or chronic obstructive pulmonary disease;
• muscle weakness or muscle cramps;
• orthostatic hypotension.

Rare (affecting less than 1 in 1,000 people):

• hearing disturbances;
• allergic rhinitis;
• reduced tear secretion (should be considered if the patient wears contact lenses);
• hepatitis, which may cause yellowing of the skin or eyes;
• changes in the results of certain blood tests related to liver function (increased AlAT and AspAT activity) or serum triglyceride levels;
• allergic reactions such as itching, facial flushing, rash, and angioedema. Immediate medical advice should be sought if severe allergic reactions occur, including: swelling of the face, neck, tongue, mouth or throat, or difficulty breathing;
• erectile dysfunction;
• nightmares, hallucinations;
• fainting.

Very rare (affecting less than 1 in 10,000 people):

• conjunctivitis (eye irritation or redness);
• alopecia (hair loss);
• occurrence or worsening of scaly skin lesions (psoriasis), psoriasiform eruptions.

If any adverse effects occur, including any possible adverse effects not listed in this leaflet, consult a doctor or pharmacist.
Reporting of adverse effects
If any adverse effects occur, including any adverse effects not mentioned in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Bisoratio

Store below 25°C. Keep in the original packaging to protect from moisture.
The medicine should be stored in a place invisible and inaccessible to children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures help protect the environment.

6. Contents of the pack and other information

What Bisoratio contains

• The active substance is bisoprolol fumarate.
• Each tablet contains either 5 mg or 10 mg of bisoprolol fumarate.
• The other ingredients are: monohydrate lactose, microcrystalline cellulose, magnesium stearate, crospovidone.

Bisoratio 5 tablets additionally contain the colouring agent PB 22812 (monohydrate lactose, iron oxide yellow (E 172)).
Bisoratio 10 tablets additionally contain the colouring agent PB 27215 (monohydrate lactose, iron oxide yellow (E 172), iron oxide red (E 172)).
What Bisoratio looks like and contents of the pack
Bisoratio tablets are round, biconvex, with a division line on one side.
The tablet can be divided into equal doses.
Pack contents: 30 or 60 tablets.
Marketing Authorisation Holder
Teva B.V.
Swensweg 5,
2031 GA Haarlem,
The Netherlands
Tel: (22) 345 93 00
Manufacturer
Merckle GmbH, Ludwig-Merckle-Str. 3, 89143 Blaubeuren, Germany
Teva Operations Poland Sp. z o.o., ul. Mogilska 80, 31-546 Kraków