BIXEBRA 7.5 mg Tablets

Contents of the leaflet

1. Leaflet attached to the packaging: patient information
2. Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.
3. Bixebra
4. 5 mg, coated tablets
   1. You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
5. What is Bixebra and what is it used for
6. Important information before taking Bixebra
   1. When not to take Bixebra
   2. Warnings and precautions
   3. Children and adolescents
   4. Bixebra and other medicines
   5. Bixebra with food and drink
   6. Pregnancy and breastfeeding
   7. Driving and using machines
   8. Bixebra contains lactose monohydrate
7. How to take Bixebra
   1. Taking a higher dose of Bixebra than recommended
   2. Missing a dose of Bixebra
   3. Stopping treatment with Bixebra
8. Possible side effects
   1. Reporting side effects
9. How to store Bixebra
10. Contents of the packaging and other information
    1. What Bixebra contains
    2. What Bixebra looks like and contents of the pack
    3. Packaging:
    4. Marketing authorization holder in Romania, the country of export:
    5. Manufacturer:
    6. Parallel importer:
    7. Repackaged by:
    8. Date of leaflet approval: 24.01.2025

Leaflet attached to the packaging: patient information

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.

Bixebra

7.5 mg, coated tablets

Ivabradine

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

• You should keep this leaflet, so that you can read it again if necessary.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Bixebra and what is it used for

Bixebra (ivabradine) is a heart medicine used in:

• symptomatic stable angina pectoris (which causes chest pain) in adult patients, whose heart rate is 70 or more beats per minute. The medicine is used in adults who do not tolerate or cannot take heart medicines called beta-adrenergic blockers. It is also used in combination with beta-adrenergic blockers in adult patients whose condition is not fully controlled with a beta-adrenergic blocker;
• chronic heart failure in adult patients, whose heart rate is 75 or more beats per minute. The medicine is used in combination with standard treatment, including beta-adrenergic blockers or when beta-adrenergic blockers are contraindicated or not tolerated.

About stable angina pectoris (usually referred to as "angina")
Stable angina pectoris is a heart disease that occurs when the heart muscle does not receive enough oxygen. The most common symptom of angina pectoris is pain or discomfort in the chest.
About chronic heart failure
Chronic heart failure is a heart disease that occurs when the heart cannot pump enough blood to the rest of the body. The most common symptoms of heart failure are shortness of breath, fatigue, tiredness, and swelling of the ankles.
How does Bixebra work?
The specific action of ivabradine, which reduces the heart rate, helps:

• to control and reduce the number of angina pectoris attacks by reducing the heart's need for oxygen
• to improve heart function and prognosis in patients with chronic heart failure.

2. Important information before taking Bixebra

When not to take Bixebra

• if the patient is allergic to ivabradine or any of the other ingredients of this medicine (listed in section 6);
• in patients whose resting heart rate is too low (below 70 beats per minute);
• in patients with cardiogenic shock (a heart condition treated in the hospital);
• in patients with rhythm disorders (sick sinus syndrome, atrioventricular block, third-degree atrioventricular block);
• in patients with recent myocardial infarction;
• in patients with very low blood pressure;
• in patients with unstable angina pectoris (a severe form with very frequent chest pain related or unrelated to exertion);
• in patients with recently worsened heart failure;
• if the heart rhythm is controlled solely by a pacemaker;
• in patients with severe liver disease;
• in patients currently taking medicines used to treat fungal infections (such as ketoconazole, itraconazole), macrolide antibiotics (e.g., josamycin, clarithromycin, telithromycin, or erythromycin given orally), medicines used to treat HIV infection (such as nelfinavir, ritonavir), or nefazodone (a medicine used to treat depression), or diltiazem, verapamil (medicines used to treat high blood pressure or angina pectoris);
• in women of childbearing age who do not use appropriate methods of contraception;
• in pregnant or breastfeeding women.

Warnings and precautions

Before starting treatment with Bixebra, you should discuss it with your doctor or pharmacist:

• if the patient has rhythm disorders (such as irregular heartbeat, palpitations, worsening chest pain) or persistent atrial fibrillation (a type of irregular heartbeat), or has a certain abnormality in the electrocardiogram (ECG), called a long QT interval;
• if the patient has symptoms such as fatigue, dizziness, or shortness of breath (which may indicate a too-low heart rate);
• if the patient has symptoms of atrial fibrillation [extremely high resting heart rate (over 110 beats per minute) or irregular heart rate, without apparent cause, difficult to measure];
• if the patient has recently had a stroke;
• if the patient has mild or moderate low blood pressure;
• if the patient has uncontrolled high blood pressure, especially after changing antihypertensive treatment;
• if the patient has severe heart failure or heart failure with a certain abnormality in the ECG, called a bundle branch block;
• if the patient has chronic retinal disease;
• if the patient has moderate liver disease;
• if the patient has severe kidney disease. In the event of any of the above situations, the doctor should be informed immediately before or during treatment with Bixebra.

Children and adolescents

This medicine should not be given to children and adolescents under 18 years of age. The available data for this age group are insufficient.

Bixebra and other medicines

You should tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take.

• fluconazole (an antifungal medicine);
• rifampicin (an antibiotic);
• barbiturates (medicines used for difficulty sleeping or in epilepsy);
• phenytoin (a medicine used in epilepsy);
• preparations of St. John's Wort (Hypericum perforatum) (herbal medicines, used to treat depression);
• medicines that prolong the QT interval, used to treat rhythm disorders or other conditions, such as:
• quinidine, disopyramide, ibutilide, sotalol, amiodarone (medicines used to treat rhythm disorders);
• bepridil (a medicine used to treat angina pectoris);
• certain types of medicines used to treat anxiety, schizophrenia, or other psychoses (such as pimozide, ziprasidone, sertindole);
• antimalarial medicines (such as mefloquine or halofantrine);
• intravenous erythromycin (an antibiotic);
• pentamidine (a medicine used to treat parasites);
• cisapride (a medicine used to treat gastroesophageal reflux);
• certain types of diuretics, which can decrease potassium levels in the blood, such as furosemide, hydrochlorothiazide, indapamide (medicines used to treat swelling, high blood pressure).

Bixebra with food and drink

You should avoid drinking grapefruit juice while taking Bixebra.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, you should consult your doctor or pharmacist before taking this medicine.

Driving and using machines

Bixebra may cause temporary vision disturbances (transient sensations of seeing strong light, see "Possible side effects"). If they occur, you should be careful while driving or operating machines, especially in situations where there may be sudden changes in lighting, especially when driving at night.

Bixebra contains lactose monohydrate

If you have been diagnosed with an intolerance to some sugars, you should contact your doctor before taking this medicine.

3. How to take Bixebra

This medicine should always be taken exactly as prescribed by your doctor or pharmacist. If you are unsure, you should consult your doctor or pharmacist.

Bixebra is available in the following strengths: 5 mg, 7.5 mg.

Bixebra should be taken during meals.

Patients with stable angina pectoris

The initial dose should not exceed one 5 mg Bixebra tablet taken twice a day. If the patient still experiences symptoms of angina pectoris and tolerates the 5 mg dose twice a day, the dose may be increased. The maintenance dose should not exceed 7.5 mg twice a day. The doctor will prescribe the appropriate dose for the individual patient. The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g., if the patient is 75 years or older), the doctor may prescribe half the dose, i.e., half a 5 mg Bixebra tablet (equivalent to 2.5 mg ivabradine) in the morning and half a 5 mg tablet in the evening.

Patients with chronic heart failure

The recommended initial dose is one 5 mg Bixebra tablet taken twice a day; if necessary, the dose may be increased to one 7.5 mg Bixebra tablet taken twice a day. The doctor will determine the appropriate dose for the individual patient. The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g., if the patient is 75 years or older), the doctor may recommend half the dose, i.e., half a 5 mg Bixebra tablet (equivalent to 2.5 mg ivabradine) in the morning and half a 5 mg tablet in the evening.

Taking a higher dose of Bixebra than recommended

After taking a large dose of Bixebra, shortness of breath or fatigue may occur, as the heart rate slows down excessively. In this case, you should immediately consult a doctor.

Missing a dose of Bixebra

If you miss a dose of Bixebra, you should take the next dose at the usual time. You should not take a double dose to make up for the missed dose.

Stopping treatment with Bixebra

Since treatment for angina pectoris or chronic heart failure is usually long-term, you should consult your doctor before stopping treatment with this medicine.

4. Possible side effects

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

The most common side effects of this medicine are dose-dependent and related to its mechanism of action:

Very common side effects (may affect more than 1 in 10 people):

vision disturbances (transient sensations of seeing strong light, most often caused by sudden changes in lighting). These disturbances are also described as auras, colorful flashes, split images, or multiple images. They usually occur within the first two months of treatment and may recur and resolve during or after treatment.

Common side effects (may affect up to 1 in 10 people):

changes in heart rate (symptoms of slowed heart rate). Symptoms occur especially within the first 2 to 3 months after starting treatment.

Other side effects have been reported:

Common side effects (may affect up to 1 in 10 people):

irregular, rapid heartbeats (atrial fibrillation), unusual sensations of heartbeat (bradycardia, ventricular extrasystoles, first-degree atrioventricular block (prolonged PQ interval on the ECG)), uncontrolled blood pressure, headaches, dizziness, and blurred vision.

Uncommon side effects (may affect up to 1 in 100 people):

palpitations and extra heartbeats, nausea, constipation, diarrhea, abdominal pain, feeling of spinning (dizziness of labyrinthine origin), breathing difficulties (shortness of breath), muscle cramps, changes in laboratory parameters: high uric acid levels in the blood, increased eosinophil count in the blood (a type of white blood cell), and increased creatinine levels in the blood (a muscle breakdown product), skin rash, angioedema (such as facial, tongue, or throat swelling, difficulty breathing or swallowing), low blood pressure, fainting, feeling of fatigue, feeling of weakness, abnormal ECG tracing, double vision, impaired vision.

Rare side effects (may affect up to 1 in 1,000 people):

hives, itching, skin redness, malaise.

Very rare side effects (may affect up to 1 in 10,000 people):

irregular heartbeat (second-degree or third-degree atrioventricular block, sick sinus syndrome).

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, 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.

5. How to store Bixebra

The medicine should be stored out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.

There are no special precautions for storage.

Medicines should not be disposed of via wastewater or household waste. You should ask your 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 Bixebra contains

• The active substance is ivabradine.
• Each coated tablet contains 7.5 mg of ivabradine (in the form of 8.085 mg ivabradine hydrochloride).
• The other ingredients (excipients) are: maltodextrin, lactose monohydrate, cornstarch, colloidal silicon dioxide, magnesium stearate, and hypromellose 3 cP in the tablet core, and hypromellose 6 cP, titanium dioxide (E 171), talc, propylene glycol, yellow iron oxide (E 172), and red iron oxide (E 172) in the tablet coating. See section 2 "Bixebra contains lactose monohydrate".

What Bixebra looks like and contents of the pack

Light pink-orange, round, slightly biconvex tablets with beveled edges, 7 mm in diameter.

Packaging:

• 14, 28, 56, 98, and 112 coated tablets in blisters in a cardboard box.

For more detailed information, you should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in Romania, the country of export:

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

Parallel importer:

InPharm Sp. z o.o.

ul. Strumykowa 28/11

03-138 Warsaw

Repackaged by:

InPharm Sp. z o.o. Services sp. k.

ul. Chełmżyńska 249

04-458 Warsaw

Authorization number in Romania, the country of export:14341/2022/04
14341/2022/02
14341/2022/01
Parallel import authorization number:105/20

Date of leaflet approval: 24.01.2025

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