BIXEBRA 5 mg Tablets

Contents of the leaflet

1. Package Leaflet: Information for the Patient
2. Bixebra, 5 mg, coated tablets
3. Bixebra, 7.5 mg, coated tablets
   1. Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.
   2. Contents of the Package Leaflet
4. What is Bixebra and what is it used for
5. 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
6. How to take Bixebra
   1. Taking a higher dose of Bixebra than recommended
   2. Missing a dose of Bixebra
   3. Stopping treatment with Bixebra
7. Possible side effects
   1. Reporting side effects
8. How to store Bixebra
9. Contents of the pack and other information
   1. What Bixebra contains
   2. What Bixebra looks like and contents of the pack
   3. Packaging:
   4. Marketing authorization holder and manufacturer

Package Leaflet: Information for the Patient

Bixebra, 5 mg, coated tablets

Bixebra, 7.5 mg, coated tablets

Ivabradine

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. 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 those not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the Package 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 pack 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 is chest pain or discomfort.
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 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 you are 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 conduction 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 exclusively by a pacemaker;
• in patients with severe liver disease;
• in patients currently taking medicines for fungal infections (such as ketoconazole, itraconazole), macrolide antibiotics (e.g., josamycin, clarithromycin, telithromycin, or oral erythromycin), HIV infection medicines (such as nelfinavir, ritonavir), or nefazodone (a medicine for depression), or diltiazem, verapamil (medicines for high blood pressure or angina);
• in women of childbearing age who do not use effective contraception;
• in pregnant or breastfeeding women.

Warnings and precautions

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

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

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.

• fluconazole (an antifungal medicine);
• rifampicin (an antibiotic);
• barbiturates (medicines used for sleep disorders or epilepsy);
• phenytoin (a medicine used for epilepsy);
• St. John's Wort preparations (Hypericum perforatum) (herbal medicines used for depression);
• medicines that prolong the QT interval used to treat heart rhythm disorders or other conditions, such as:
• quinidine, disopyramide, ibutilide, sotalol, amiodarone (medicines used to treat heart rhythm disorders);
• bepridil (a medicine used to treat angina);
• 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 for parasites);
• cisapride (a medicine for gastroesophageal reflux);
• certain types of diuretics that may decrease potassium levels in the blood, such as furosemide, hydrochlorothiazide, indapamide (medicines used to treat swelling, high blood pressure).

Bixebra with food and drink

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, ask your doctor or pharmacist for advice 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 this occurs, be cautious while driving or operating machinery, especially in situations where there may be sudden changes in lighting, especially when driving at night.

Bixebra contains lactose

If you have been told that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Bixebra

Always take this medicine exactly as your doctor or pharmacist has told you.

In case of doubt, ask your doctor or pharmacist.

Bixebra should be taken during meals.

The 5 mg Bixebra coated tablet can be divided into equal doses.

Patients with stable angina pectoris

The initial dose should not exceed one 5 mg Bixebra tablet twice daily. If the patient still experiences angina symptoms and tolerates the 5 mg dose twice daily, the dose may be increased. The maintenance dose should not exceed 7.5 mg twice daily. Your doctor will prescribe the appropriate dose for you. 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 twice daily; if necessary, the dose may be increased to one 7.5 mg Bixebra tablet twice daily. Your doctor will determine the appropriate dose for you. 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, take the next dose at the usual time. Do not take a double dose to make up for the missed dose.

Stopping treatment with Bixebra

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

If you feel that the effect of Bixebra is too strong or too weak, consult your doctor or pharmacist.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine 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, after which they may recur and disappear during therapy 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 sensation of heartbeat (bradycardia, ventricular extrasystoles, first-degree atrioventricular block (prolonged PQ interval on ECG)), uncontrolled high 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 tiredness, 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 those not listed in this leaflet, please inform your doctor or pharmacist. 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.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bixebra

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton after "EXP". The expiry date refers to the last day of that month.

There are no special storage precautions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Bixebra contains

• The active substance is ivabradine. Bixebra, 5 mg, coated tablets: each coated tablet contains 5 mg ivabradine (equivalent to 5.390 mg ivabradine hydrochloride). Bixebra, 7.5 mg, coated tablets: each coated tablet contains 7.5 mg ivabradine (equivalent to 8.085 mg ivabradine hydrochloride).
• The other ingredients (excipients) are: maltodextrin, lactose monohydrate, cornstarch, colloidal silicon dioxide, magnesium stearate (E 470b), 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".

What Bixebra looks like and contents of the pack

Bixebra, 5 mg, coated tablets: the tablets are pink-orange, rectangular, slightly convex coated tablets with a dividing line on one side; tablet dimensions: 8 mm x 4.5 mm. The tablet can be divided into equal doses.

Bixebra, 7.5 mg, coated tablets: the tablets are pink-orange, round, slightly convex coated tablets with beveled edges, 7 mm in diameter.

Packaging:

• 14, 28, 30, 56, 60, 90, 98, 100, 112, and 180 coated tablets in blisters in a cardboard box;
• 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 90 x 1, 98 x 1, 100 x 1, 112 x 1, and 180 x 1 coated tablet in single-dose blisters in a cardboard box. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

To obtain more detailed information on the names of medicinal products in other EU member states, please contact the representative of the marketing authorization holder:

KRKA-POLSKA Sp. z o.o.

ul. Równoległa 5

02-235 Warsaw

Tel. 22 57 37 500.

Date of last revision of the leaflet:27.07.2023