Patient Information Leaflet

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

Keep this leaflet. You may need to read it again.
If you have any further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not give it to others. It may harm someone else, 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 immediately. See section 4.

Table of Contents

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 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. It is used in adults who are unable to tolerate or cannot take heart medications known as beta-blockers. It may also be used in combination with beta-blockers in adult patients whose condition is not adequately controlled with beta-blockers alone;
chronic heart failure in adult patients with a heart rate of 75 beats per minute or higher. It 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 condition in which the heart is unable to pump enough blood to meet the body's needs. The most common symptoms of heart failure are shortness of breath, fatigue, tiredness, and swelling of the ankles.

How Bixebra works
Ivabradine specifically reduces heart rate, which 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 (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 medicines used to treat fungal infections (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 age who are not using appropriate methods of contraception;
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 certain abnormality in the electrocardiogram (ECG), known as 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 develops symptoms of atrial fibrillation [very 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 and 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 of its use may be necessary:

fluconazole (an antifungal medicine);
rifampicin (an antibiotic);
barbiturates (medicines used for sleep difficulties or epilepsy);
phenytoin (a medicine used for epilepsy);
St John's wort (Hypericum perforatum) preparations (herbal medicines used to treat 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 (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 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 become pregnant, 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 age should not take Bixebra unless they are using appropriate methods of contraception (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 such symptoms 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 use Bixebra

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
Bixebra is available in the following strengths: 5 mg, 7.5 mg.
Bixebra should be taken with food.

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. 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 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 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 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 prescribed
After taking a large dose of Bixebra, shortness of breath or fatigue may occur due to excessive slowing of the heart rate. In such a case, seek medical advice immediately.

Missing a dose of Bixebra
If a dose of Bixebra is missed, the next dose should be taken at the usual time. A double dose should not be taken to make up for the missed dose.

Stopping Bixebra
As treatment for angina pectoris or chronic heart failure is usually long-term, consult a doctor before stopping this medicine.

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 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 commonly 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 or after therapy.
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, headaches, dizziness, and 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 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 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 1000 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 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 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 instructions apply.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Following this advice helps protect the environment.

6. Contents of the pack and other information

What Bixebra contains

The active substance is ivabradine.
Each coated tablet contains 7.5 mg of ivabradine (as 8.085 mg 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, round, slightly biconvex tablets with bevelled edges, 7 mm in diameter.
Pack sizes:

14, 28, 56, 98 and 112 coated tablets in blisters packed in 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:
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: 14341/2022/04
14341/2022/02
14341/2022/01
Parallel import authorisation number: 105/20