Package leaflet: Information for the patient

Bixebra, 5 mg, film-coated tablets
Bixebra, 7.5 mg, film-coated tablets
Ivabradinum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

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 a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

What Bixebra is and what it is used for
What you need to know 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 heart medication used for:

symptomatic stable angina (which causes chest pain) in adult patients with a heart rate of 70 beats per minute or more. 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 more. The medicine is used in combination with standard therapy, including beta-blockers, or when beta-blockers are contraindicated or not tolerated.

About stable angina (often 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 pain or discomfort in the chest.

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 heart rate-reducing action of ivabradine helps:

control and reduce the number of angina attacks by decreasing the heart's oxygen demand
improve heart function and outcomes 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 (a severe form with frequent chest pain occurring with or without exertion);
in patients whose heart failure 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 orally administered erythromycin), medications used to treat HIV infection (such as nelfinavir, ritonavir) or nefazodone (a medication used to treat depression), or diltiazem, verapamil (medications used to treat high blood pressure or angina);
in women of childbearing age 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 permanent 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 too low a heart rate);
if the patient experiences 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 blood pressure, especially after a change in 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. Available data in this age group are insufficient.

Bixebra with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Inform your doctor if taking any of the following medicines, as it may be necessary to adjust the dose of Bixebra or closely monitor its use:

fluconazole (an antifungal medicine);
rifampicin (an antibiotic);
barbiturates (medicines used for difficulty sleeping or in 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);
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").
Contact your doctor if pregnancy occurs during treatment with Bixebra.
Women of childbearing age 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 using machines
Bixebra may cause transient visual disturbances (brief sensations of seeing 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
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 use Bixebra

This medicine should always be used according to the instructions given by the doctor or pharmacist. If in doubt,
consult the doctor or pharmacist.
Bixebra tablets should be taken during meals.
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 Bixebra tablet taken twice daily. If symptoms of angina pectoris 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. 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 of age or older), the doctor may prescribe half the dose, i.e. half a 5 mg Bixebra tablet (corresponding 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 initial dose is one 5 mg Bixebra tablet taken twice daily; if necessary, the dose may be increased to one 7.5 mg Bixebra tablet taken twice daily. 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 of age or older), the doctor may recommend half the dose, i.e. half a 5 mg Bixebra tablet (corresponding to 2.5 mg of ivabradine) in the morning and half a 5 mg tablet in the evening.

Taking more Bixebra than prescribed
After taking a larger than recommended dose of Bixebra, shortness of breath or feeling tired may occur due to excessive slowing of the heart rate. In such a case, consult a doctor immediately.

Missing a dose of Bixebra
If a dose of Bixebra is missed, 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 of angina pectoris or chronic heart failure is usually long-term, consult the doctor before stopping this medicine.
If you feel that the effect of Bixebra is too strong or too weak, consult the doctor or pharmacist.
If you have any further doubts about using this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
The most common adverse reactions of this medicine are dose-dependent and are related to its mechanism of action:
Very common adverse reactions (may occur in more than 1 in 10 patients):
visual disturbances (transient sensations of seeing bright light, most frequently caused by sudden changes in light intensity). These disturbances are also described as halos, colored flashes, split 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.
Other adverse reactions have also been reported:
Common adverse reactions (may occur in less than 1 in 10 patients):
change in heart function (symptoms of slowed heart rate). Symptoms occur particularly within the first 2 to 3 months after starting treatment.
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), difficulty breathing (dyspnea), muscle cramps, changes in laboratory parameters: high blood uric acid levels, increased number of eosinophils in blood (a type of white blood cells), 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 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 atriovent游戏副本

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 carton after the word "EXP". The expiry date refers to the last day of the stated month.
There are no special storage instructions.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures 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 of ivabradine (equivalent to 5.390 mg of ivabradine hydrochloride). Bixebra 7.5 mg, coated tablets: each coated tablet contains 7.5 mg of ivabradine (equivalent to 8.085 mg of ivabradine hydrochloride).
The other components (excipients) are: maltodextrin, monohydrate lactose, corn starch, anhydrous colloidal silicon dioxide, 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".

What Bixebra looks like and contents of the pack
Bixebra 5 mg, coated tablets: the coated tablets are light pink-orange, rectangular, slightly biconvex tablets with a break 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 coated tablets are light pink-orange, round, slightly biconvex tablets with bevelled edges, 7 mm in diameter.
Packaging:

14, 28, 30, 56, 60, 90, 98, 100, 112 and 180 coated tablets in blister packs contained in a cardboard box;
14 × 1, 28 × 1, 30 × 1, 56 × 1, 60 × 1, 90 × 1, 98 × 1, 100 × 1, 112 × 1 and 180 × 1 coated tablet in unit dose blisters contained in a cardboard box. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
For further information about the names of medicinal products in other European Economic Area countries, please contact the representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Tel. 22 57 37 500.