IVABRADINE COMBIX 7.5 mg FILM-COATED TABLETS

Introduction

Patient Information Leaflet

Ivabradina Combix7.5 mg film-coated tablets EFG

Read all of this leaflet carefully before you start 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 you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What Ivabradina Combix is and what it is used for
2. What you need to know before you take Ivabradina Combix
3. How to take Ivabradina Combix
4. Possible side effects
5. Storing Ivabradina Combix
6. Contents of the pack and other information

1. What Ivabradina Combix is and what it is used for

Ivabradina is a heart medicine used to treat:

• Stable angina pectoris (which causes chest pain) in adult patients whose heart rate is greater than or equal to 70 beats per minute. It is used in adult patients who cannot tolerate or are unable to take heart medications called beta-blockers. It is also used in combination with beta-blockers in adult patients whose disease is not completely controlled with a beta-blocker.
• Chronic heart failure in adult patients whose heart rate is greater than or equal to 75 beats per minute. It is used in combination with standard treatment, including treatment with beta-blockers, or when beta-blockers are contraindicated or not tolerated.

About stable angina pectoris (commonly known as "angina")

Stable angina pectoris is a heart disease that occurs when the heart does not receive enough oxygen. It usually appears between the ages of 40 and 50. The most frequent symptom of angina is chest pain or discomfort. Angina is more likely to occur when the heart beats faster in situations such as exercise, emotion, exposure to cold, or after eating. This increase in heart rate can cause chest pain in people who suffer from angina.

About chronic heart failure

Chronic heart failure is a heart disease that occurs when your heart is unable to pump enough blood to the rest of your body. The most frequent symptoms of heart failure are difficulty breathing, fatigue, tiredness, and swelling of the ankles.

How Ivabradina works

Ivabradina works mainly by reducing the heart rate by some beats per minute. This reduces the heart's need for oxygen, especially in situations where angina attacks are more likely to occur. In this way, Ivabradina tablets help control and reduce the number of angina attacks.

Also, since a high heart rate negatively affects the functioning of the heart and vital prognosis in patients with chronic heart failure, the specific heart rate-lowering action of Ivabradina helps improve heart function and vital prognosis in these patients.

2. What you need to know before you take Ivabradina Combix

Do not take Ivabradina

• if you are allergic to ivabradina or any of the other ingredients of this medicine (listed in section 6);
• if your resting heart rate before treatment is too slow (below 70 beats per minute);
• if you have cardiogenic shock (a heart problem treated in the hospital);
• if you have a heart rhythm disorder;
• if you are having a heart attack;
• if you have very low blood pressure;
• if you have unstable angina (a severe type of angina that occurs very frequently with or without exercise);
• if you have recently worsened heart failure;
• if your heart rate is exclusively determined by your pacemaker;
• if you have severe liver problems;
• if you are taking medications for the treatment of fungal infections (such as ketoconazole, itraconazole), antibiotics of the macrolide group (such as josamycin, clarithromycin, telithromycin, or erythromycin administered orally), medications for the treatment of HIV (such as nelfinavir, ritonavir), or nefazodone (a medication for the treatment of depression) or diltiazem, verapamil (used for the treatment of high blood pressure or angina pectoris);
• if you are a woman of childbearing age and do not use reliable contraceptive methods;
• if you are pregnant or trying to become pregnant;
• if you are breastfeeding.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Ivabradina if:

• you have heart rhythm disorders (such as irregular heartbeat, palpitations, increased chest pain) or sustained atrial fibrillation (a type of irregular heartbeat), or an abnormality in the electrocardiogram (ECG) called "QT prolongation syndrome",
• you have symptoms such as fatigue, dizziness, or difficulty breathing (this may mean that your heart is beating too slowly),
• you have symptoms of atrial fibrillation (unusually high resting pulse (above 110 beats per minute) or irregular, without any apparent reason, making it difficult to measure),
• you have had a recent stroke (brain attack),
• you have mild to moderate low blood pressure,
• you have uncontrolled high blood pressure, especially after a change in your antihypertensive treatment,
• you have severe heart failure or heart failure with an ECG abnormality called "branch block",
• you have chronic eye retinal disease,
• you have moderate liver problems,
• you have severe kidney problems.

If you meet any of these conditions, consult your doctor immediately before or during treatment with Ivabradina.

Children

Ivabradina is not intended for use in children and adolescents under 18 years of age.

Using Ivabradina with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Make sure to inform your doctor if you are taking any of the following medicines, as a dose adjustment of Ivabradina or monitoring may be necessary:

• fluconazole (an antifungal medication)
• rifampicin (an antibiotic)
• barbiturates (for sleep problems or epilepsy)
• phenytoin (for epilepsy)
• Hypericum perforatumor St. John's Wort (a medicinal plant for the treatment of depression).
• Medicines that prolong the QT interval for the treatment of heart rhythm disorders or other conditions:
• • quinidine, disopyramide, ibutilide, sotalol, amiodarone (for the treatment of heart rhythm disorders)
  • bepridil (for the treatment of angina pectoris)
  • certain types of medications for the treatment of anxiety, schizophrenia, or other psychoses (such as pimozide, ziprasidone, sertindol)
  • antimalarial medications (such as mefloquine or halofantrine)
  • intravenous erythromycin (an antibiotic)
  • pentamidine (an antiparasitic medication)
  • cisapride (for gastroesophageal reflux).
• Certain types of diuretics that can cause a reduction in potassium levels in the blood, such as furosemide, hydrochlorothiazide, indapamide (used to treat edema, high blood pressure).

Taking Ivabradina with food and drinks

Avoid grapefruit juice during treatment with Ivabradina.

Pregnancy and breastfeeding

Do not take Ivabradina if you are pregnant or plan to become pregnant (see "Do not take Ivabradina").

If you are pregnant and have taken Ivabradina, consult your doctor.

Do not take Ivabradina if you are of childbearing age and do not use reliable contraceptive methods (see "Do not take Ivabradina").

Do not take Ivabradina if you are breastfeeding (see "Do not take Ivabradina"). Talk to your doctor if you are breastfeeding or plan to start breastfeeding, as breastfeeding should be discontinued if you are taking Ivabradina.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

Ivabradina may cause transient visual phenomena (a brief increase in brightness, usually caused by sudden changes in light intensity). If this happens, be careful when driving or using machinery in situations where sudden changes in light intensity may occur, especially when driving at night.

3. How to take Ivabradina Combix

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

Ivabradina should be taken with breakfast and dinner.

If you are being treated for stable angina pectoris

The initial dose should not exceed one 5 mg Ivabradina tablet twice a day. If you still have symptoms of angina and have tolerated the 5 mg dose twice a day, the dose may be increased. The maintenance dose should not exceed 7.5 mg twice a day. Your doctor will prescribe the correct dose for you. The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g., if you are an elderly patient), your doctor may prescribe half the dose, i.e., half a 5 mg Ivabradina tablet (corresponding to 2.5 mg of Ivabradina) in the morning and half a 5 mg tablet in the evening.

If you are being treated for chronic heart failure

The recommended initial dose is one 5 mg Ivabradina tablet twice a day, which may be increased if necessary to one 7.5 mg Ivabradina tablet twice a day. Your doctor will decide the suitable dose for you. The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g., if you are an elderly patient), your doctor may prescribe half the dose, i.e., half a 5 mg Ivabradina tablet (corresponding to 2.5 mg of Ivabradina) in the morning and half a 5 mg tablet in the evening.

If you take more Ivabradina than you should

Taking too much Ivabradina may make you feel tired or have difficulty breathing because your heart is beating too slowly. If this happens, contact your doctor immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Ivabradina

If you forget to take a dose of Ivabradina, take the next dose at the scheduled time. Do not take a double dose to make up for forgotten doses.

If you stop taking Ivabradina

Generally, treatment for angina pectoris or chronic heart failure is lifelong, so you should consult your doctor before stopping this medication.

If you think the action of Ivabradina is too strong or too weak, tell your doctor or pharmacist.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequency of the possible side effects listed below is defined using the following system:

Very common: may affect more than 1 in 10 people.

Common: may affect up to 1 in 10 people.

Uncommon: may affect up to 1 in 100 people.

Rare: may affect up to 1 in 1,000 people.

Very rare: may affect up to 1 in 10,000 people.

Frequency not known: frequency cannot be estimated from the available data.

The most common side effects with this medicine are dose-dependent and related to its mechanism of action:

Very common:

Transient visual phenomena (brief moments of increased brightness, usually caused by sudden changes in light intensity). They can also be described as a halo, flashes of color, image decomposition, or multiple images. These usually appear during the first two months of treatment, after which they may occur repeatedly and resolve during or after treatment.

Common:

Modification of heart function (symptoms are a slowing of the heart rate). This occurs especially in the first 2 to 3 months after starting treatment.

Other side effects have also been reported:

Common:

Irregular rapid heart contraction, sensation of abnormal heartbeat, uncontrolled high blood pressure, headache, dizziness, and blurred vision (cloudy vision).

Uncommon:

Palpitations and extra heartbeats, sensation of dizziness (nausea), constipation, diarrhea, abdominal pain, sensation of spinning (vertigo), difficulty breathing (dyspnea), muscle cramps, changes in laboratory tests: elevated blood uric acid levels, excess eosinophils (a type of white blood cell), and elevated creatinine levels in blood (a muscle breakdown product), skin rash, angioedema (such as facial swelling, tongue or throat swelling, difficulty breathing or swallowing), low blood pressure, fainting, feeling of tiredness, feeling of weakness, abnormal electrocardiogram, double vision, visual disturbance.

Rare:

Urticaria, itching, skin redness, malaise.

Very rare:

Irregular heartbeats.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Ivabradina Combix

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

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

6. Contents of the pack and other information

Composition of Ivabradina Combix

• The active substance is ivabradina. Each film-coated tablet contains 7.5 mg of ivabradina.
• The other ingredients are:

Core of the tablet: Lactose, microcrystalline cellulose (460i), magnesium stearate (470b), pregelatinized corn starch (1500 LM), sodium starch glycolate type A potato, anhydrous colloidal silica.

Coating: Opadry Beige 03G570000.

Appearance of the product and pack contents

Film-coated tablets, light brown in color, round, with the mark "2" on one face and smooth on the other.

Ivabradina Combix 7.5 mg is available in blister packs, in packs of 56 tablets.

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

or

Pharmex Advanced Laboratories S.L.

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

Date of last revision of this leaflet:January 2017

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/