Bixebra

Patient Information Leaflet

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

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

Table of Contents

1. What Bixebra is and what it is used for
2. What you need to know 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 Bixebra is and what it is used for

Bixebra (ivabradine) is a heart medication used for:

• symptomatic stable angina (which causes chest pain) in adult patients with a resting heart rate of 70 beats per minute or higher. Bixebra is used in adults who do not tolerate or cannot take a group of heart medications called 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 resting heart rate of 75 beats per minute or higher. Bixebra 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 condition 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 condition that occurs 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 Bixebra works
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 who have recently had a myocardial infarction (heart attack);
• in patients with very low blood pressure;
• in patients with unstable angina (a severe form of angina with frequent chest pain occurring with or without exertion);
• in patients with recently worsened heart failure;
• if heart activity is solely driven by a cardiac pacemaker;
• in patients with severe liver disease;
• in patients currently taking antifungal medicines (such as ketoconazole, itraconazole), macrolide antibiotics (e.g. josamycin, clarithromycin, telithromycin or oral erythromycin), 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);
• in women of childbearing potential who are not using appropriate contraceptive methods;
• in pregnant women or women planning to become pregnant;
• 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 persistent atrial fibrillation (a type of irregular heartbeat), or has a certain abnormality in the electrocardiogram (ECG) called long QT syndrome;
• if the patient experiences symptoms such as fatigue, dizziness or shortness of breath (which may indicate that the heart rate is too low);
• if the patient develops symptoms of atrial fibrillation [extremely high resting heart rate (over 110 beats per minute) or irregular pulse without apparent cause, difficult to measure];
• if the patient has recently had a stroke;
• if the patient has mild or moderately low blood pressure;
• if the patient has uncontrolled hypertension, especially after changing antihypertensive treatment;
• if the patient has severe heart failure or heart failure with a certain ECG abnormality called bundle branch block;
• if the patient has chronic retinal disease;
• if the patient has moderately severe liver disease;
• if 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. Data available for this age group are insufficient.

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

• fluconazole (an antifungal medicine);
• rifampicin (an antibiotic);
• barbiturates (medicines used for sleep problems or epilepsy);
• phenytoin (a medicine used for epilepsy);
• St John's wort (Hypericum perforatum) preparations (herbal medicines used for 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);
• 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 the blood, such as furosemide, hydrochlorothiazide, indapamide (medicines used to treat oedema, 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 have a baby, she should consult her doctor or pharmacist before using this medicine.
Do not use Bixebra during pregnancy or if the patient is planning to have a child (see "When not to use Bixebra").
Inform your doctor immediately 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 while 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 using machines
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 lactose monohydrate
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 you are unsure,
you should consult your doctor or pharmacist.
Bixebra is available in the following doses: 5 mg and 7.5 mg.
Bixebra tablets should be taken with food.
The 5 mg coated tablet of Bixebra can 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 patient tolerates the 5 mg dose twice daily well, 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 a dose, i.e. half of a 5 mg Bixebra tablet (corresponding to 2.5 mg of ivabradine) in the morning and half of 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 a dose, i.e. half of a 5 mg Bixebra tablet (corresponding to 2.5 mg of ivabradine) in the morning and half of a 5 mg tablet in the evening.

Taking more Bixebra than recommended
After taking a large dose of Bixebra, shortness of breath or feeling tired may occur due to excessive slowing of the heart rate. In such a case, you should contact your doctor immediately.

If you forget to take 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, you should consult your doctor before stopping this medicine.

If you feel that the effect of Bixebra is too strong or too weak, you should 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 all medicines, this medicine may cause adverse reactions, although not everyone will experience them.
The most common adverse reactions of this medicine are dose-dependent and 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 perception of bright light, most frequently triggered by
sudden changes in light intensity). These disturbances are also described as aura, coloured flashes,
double images or multiple images. They usually occur within the first two
months of treatment, may recur thereafter, and may 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). 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 eyesight).
Uncommon adverse reactions (may occur in less than 1 in 100 patients):
palpitations and extra heartbeats, nausea, constipation, diarrhoea, abdominal pain, sensation of spinning (vertigo), difficulty breathing (dyspnoea), muscle cramps, changes in laboratory parameters: high blood uric acid levels, increased blood eosinophil count (a type of white blood cell), increased blood creatinine levels (a muscle breakdown product), skin rash, angioedema (such as swelling of the face, tongue or throat, difficulty breathing or swallowing), low blood pressure, fainting, feeling of fatigue, feeling of weakness, abnormal heart activity recording visible on ECG, double vision, impaired vision.
Rare adverse reactions (may occur in less than 1 in 1,000 patients):
urticaria, itching, redness of the skin, 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 adverse reactions not listed
in this leaflet, inform your doctor, pharmacist or nurse. 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
By reporting adverse reactions, more information on the safety of the medicine can be collected.

5. How to store Bixebra

Keep this medicine 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 stated month.
No special storage conditions apply.
Medicines must 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 (in the form of 5.390 mg of ivabradine hydrochloride).
• The other ingredients (excipients) are: maltodextrin, lactose monohydrate, maize starch, colloidal anhydrous silica, magnesium stearate (E 470b) 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 lactose monohydrate".

What Bixebra looks like and contents of the pack
Bixebra 5 mg, coated tablets (tablets): 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.
Packaging:
56 coated tablets in blisters within a cardboard box.
For more detailed information, please contact the marketing authorisation holder 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:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Marketing authorisation number in Romania, country of export: 14340/2022/04
Parallel import authorisation number: 107/26