Package leaflet: Information for the patient

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Bixebra
5 mg, coated tablets
Ivabradine
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

What Bixebra is and what it is used for
Important information before taking Bixebra
How to take Bixebra
Possible side effects
How to store Bixebra
Contents of the pack and other information

1. What Bixebra is and what it is used for

Bixebra (ivabradine) is a cardiac medicine used for:

symptomatic stable angina (which causes chest pain) in adult patients with a heart rate of 70 beats per minute or higher. The medicine is used in adults who cannot tolerate or are unable to take heart medications known as beta-blockers. It is also used in combination with beta-blockers in adult patients whose condition is not fully controlled with a beta-blocker alone;
chronic heart failure in adult patients with a heart rate of 75 beats per minute or higher. The medicine is used in combination with standard therapy, including beta-blockers, or when beta-blockers are contraindicated or not tolerated.

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

control and reduce the number of angina attacks by decreasing the heart's oxygen demand
improve heart function and prognosis in patients with chronic heart failure.

2. Important information before using Bixebra

When not to use 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 hospital);
in patients with heart rhythm disorders (sick sinus syndrome, sinoatrial block, third-degree atrioventricular block);
in patients with recent myocardial infarction;
in patients with severely low blood pressure;
in patients with unstable angina pectoris (severe form with frequent chest pain occurring at rest or during exertion, with or without physical effort);
in patients with heart failure that has recently worsened;
if heart activity is solely driven by a cardiac pacemaker;
in patients with severe liver disease;
in patients currently taking antifungal medications (such as ketoconazole, itraconazole), macrolide antibiotics (e.g. josamycin, clarithromycin, telithromycin, or oral erythromycin), HIV treatment drugs (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 potential who are not using appropriate contraceptive methods;
in pregnant women or women planning pregnancy;
in breastfeeding women.

Warnings and precautions
Before starting treatment with Bixebra, discuss with your doctor or pharmacist if:

the patient has heart rhythm disorders (such as irregular heartbeat, palpitations, worsening chest pain), or has a specific abnormality in the electrocardiogram (ECG) called long QT syndrome;
the patient experiences symptoms such as fatigue, dizziness, or shortness of breath (which may indicate too low a heart rate);
the patient develops symptoms of atrial fibrillation [extremely high resting heart rate (above 110 beats per minute) or irregular pulse without apparent cause, difficult to measure];
the patient has recently had a stroke;
the patient has mild or moderately low blood pressure;
the patient has uncontrolled blood pressure, especially after a change in antihypertensive treatment;
the patient has severe heart failure or heart failure with a specific ECG abnormality called bundle branch block;
the patient has chronic retinal disease;
the patient has moderate to severe liver disease;
the patient has severe kidney disease.
If any of the above conditions occur, inform your doctor 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. Available data in this age group are insufficient.

Bixebra with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Inform your doctor if you are taking any of the following medicines, as dose adjustment of Bixebra or close monitoring of treatment may be required:

fluconazole (an antifungal medicine);
rifampicin (an antibiotic);
barbiturates (medicines used for sleep difficulties or epilepsy);
phenytoin (a medicine used in epilepsy);
St John's wort (Hypericum perforatum) preparations (herbal medicines used to treat depression);
QT-prolonging medicines 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 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 (an antiparasitic medicine);
cisapride (a medicine for gastroesophageal reflux);
certain types of diuretics that may reduce potassium levels in blood, such as furosemide, hydrochlorothiazide, indapamide (medicines used to treat edema, high blood pressure).

Bixebra with food and drink
Avoid drinking grapefruit juice during treatment with Bixebra.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Do not use Bixebra during pregnancy or if the patient plans to become pregnant (see "When not to use Bixebra").
Inform your doctor if pregnancy occurs during treatment with Bixebra.
Women of childbearing potential should not take Bixebra unless they are using appropriate contraceptive methods (see "When not to use Bixebra").
Do not take Bixebra during breastfeeding (see "When not to use Bixebra"). The patient should consult her doctor if she is breastfeeding or intends to breastfeed, as breastfeeding must be discontinued if the patient is taking Bixebra.

Driving and operating machinery
Bixebra may cause transient visual disturbances (brief sensations of bright light in the visual field, see "Possible side effects"). If these occur, caution should be exercised when driving or operating machinery, especially in situations involving sudden changes in lighting intensity, particularly when driving at night.

Bixebra contains monohydrate lactose
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult their doctor before taking this medicine.

3. How to take Bixebra

This medicine should always be taken exactly as directed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
Bixebra should be taken during meals.
Bixebra is available in the following strengths: 5 mg, 7.5 mg.
The 5 mg coated tablet of Bixebra may be divided into equal doses.

Patients with stable angina pectoris
The initial dose should not exceed one 5 mg tablet of Bixebra taken twice daily. If angina symptoms
persist and the 5 mg dose twice daily is well tolerated, 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 of age or older), the doctor may prescribe half the dose, i.e. half a 5 mg tablet of
Bixebra (equivalent to 2.5 mg of ivabradine) in the morning and half a 5 mg tablet in the evening.

Patients with chronic heart failure
The usual recommended starting dose is one 5 mg tablet of Bixebra taken twice daily. If necessary,
the dose may be increased to one 7.5 mg tablet of Bixebra taken 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 of age or older), the doctor may recommend half the
dose, i.e. half a 5 mg tablet of Bixebra (equivalent to 2.5 mg of ivabradine) in the morning and half
a 5 mg tablet in the evening.

Taking more Bixebra than recommended
If a large dose of Bixebra is taken, shortness of breath or fatigue may occur due to excessive
slowing of the heart rate. In such a case, consult your doctor immediately.

If you miss 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 Bixebra
Since treatment for angina pectoris or chronic heart failure is usually long-term, do not stop taking
this medicine without first consulting 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 about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although they do not occur in everyone.
The most common adverse reactions of this medicine are dose-dependent and are related to the
mechanism of action of the medicine:
Very common adverse reactions (may occur in more than 1 in 10 patients):
visual disturbances (transient visual perceptions of bright light, most commonly triggered by
sudden changes in light intensity). These disturbances are also described as halos, colored flashes,
double images or multiple images. They usually occur within the first two months of treatment,
after which they may recur and resolve during therapy or after treatment.
Common adverse reactions (may occur in less than 1 in 10 patients):
changes in heart function (symptoms of slowed heart rate). These symptoms occur particularly
within the first 2 to 3 months after starting treatment.
Other adverse reactions have also been reported:
Common adverse reactions (may occur in less than 1 in 10 patients):
irregular, rapid heartbeats (atrial fibrillation), unusual awareness of heartbeat (bradycardia, ventricular extrasystoles, first-degree atrioventricular block (prolonged PQ interval on ECG)), uncontrolled blood pressure, headache, dizziness and blurred vision (blurred vision).
Uncommon adverse reactions (may occur in less than 1 in 100 patients):
palpitations and extra heartbeats, nausea, constipation, diarrhea, abdominal pain, sensation of spinning (vertigo), breathing difficulties (dyspnea), muscle cramps, changes in laboratory parameters: high levels of uric acid in blood, increased number of eosinophils in blood (a type of white blood cells), increased creatinine levels in blood (a product of muscle breakdown), skin rash, angioedema (such as facial, tongue or throat swelling, breathing or swallowing difficulties), low blood pressure, fainting, feeling of fatigue, feeling of weakness, abnormal heart activity visible on ECG recording, double vision, impaired vision.
Rare adverse reactions (may occur in less than 1 in 1,000 patients):
urticaria, itching, skin redness, malaise.
Very rare adverse reactions (may occur in less than 1 in 10,000 patients):
irregular heartbeat (second-degree atrioventricular block, third-degree atrioventricular block, sick sinus syndrome).
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions 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.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store the medicine Bixebra

Keep this medicine out of the 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 stated month.
No special storage conditions are required.
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.
Each coated tablet contains 5 mg of ivabradine (equivalent to 5.390 mg of ivabradine hydrochloride).
The other ingredients (excipients) are: maltodextrin, monohydrate lactose, maize starch, colloidal anhydrous silica, magnesium stearate and hypromellose 3 cP in the tablet core; 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 monohydrate lactose".

What Bixebra looks like and contents of the pack
Light pink-orange, rectangular, slightly biconvex coated tablets with a division line on one side; tablet dimensions: 8 mm x 4.5 mm. The tablet can be divided into equal doses.
Pack sizes:
14, 28, 56, 98 and 112 coated tablets in blisters packed in a cardboard box.
For more detailed information, please contact the responsible party or the parallel importer.
Marketing Authorisation Holder in Romania, 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, Poland
Repackaged by:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw, Poland
Marketing Authorisation numbers in Romania, country of export: 14340/2022/04
14340/2022/01
14340/2022/02
Parallel import authorisation number: 111/20