Ivabradine Combix 7.5 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Ivabradina Combix 7.5 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, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Ivabradina Combix tablets are and what they are used for
2. What you need to know before taking Ivabradina Combix tablets
3. How to take Ivabradina Combix tablets
4. Possible side effects
5. How to store Ivabradina Combix tablets
6. Contents of the pack and other information

1. What ivabradine Combix tablets are and what they are used for

Ivabradine is a heart medication used to treat:

• Symptomatic stable angina (which causes chest pain) in adult patients with a heart rate of 70 beats per minute or higher. It is used in adult patients who cannot tolerate or cannot take heart medications known as beta-blockers. It is also used in combination with beta-blockers in adult patients whose condition is not adequately controlled with a beta-blocker 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 treatment with beta-blockers, or when beta-blockers are contraindicated or not tolerated.

About stable angina (commonly known as “angina”)

Stable angina is a heart disease that occurs when the heart does not receive enough oxygen. It usually develops between the ages of 40 and 50. The most common symptom of angina is chest pain or discomfort. Angina is more likely to occur when the heart beats faster, such as during physical exertion, emotional stress, exposure to cold, or after eating. This increase in heart rate may trigger chest pain in people with angina.

About chronic heart failure

Chronic heart failure is a heart disease that occurs when your heart cannot pump enough blood to the rest of the body. The most common symptoms of heart failure are shortness of breath, fatigue, tiredness, and swelling of the ankles.

How does Ivabradine work?

Ivabradine works primarily by reducing the heart rate by several beats per minute. This decreases the heart's oxygen demand, particularly in situations where an angina attack is more likely to occur. Thus, Ivabradine tablets help control and reduce the number of angina attacks.

Additionally, since elevated heart rate negatively affects heart function and vital prognosis in patients with chronic heart failure, the specific heart rate-lowering action of Ivabradine helps improve heart function and vital prognosis in these patients.

2. What you need to know before taking Ivabradina Combix tablets

Do not take Ivabradina tablets

• if you are allergic to ivabradine 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 are suffering from cardiogenic shock (a heart condition treated in 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 in which chest pain occurs frequently, with or without exercise);
• if you have heart failure that has recently worsened;
• if your heart rate is solely determined by your pacemaker;
• if you have severe liver problems;
• if you are taking medicines for fungal infections (such as ketoconazole, itraconazole), macrolide antibiotics (such as josamycin, clarithromycin, telithromycin or oral erythromycin), medicines to treat HIV infections (such as nelfinavir, ritonavir) or nefazodone (a medicine for treating depression), or diltiazem, verapamil (used to treat high blood pressure or angina);
• 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

Talk to your doctor or pharmacist before starting to take Ivabradina tablets:

• 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 on the electrocardiogram (ECG) called "Long QT syndrome";
• if you experience symptoms such as fatigue, dizziness, or difficulty breathing (this may mean your heart is beating too slowly);
• if you develop symptoms of atrial fibrillation (unusually high resting pulse (over 110 beats per minute) or irregular pulse, without apparent reason, making it difficult to measure);
• if you have recently had a stroke (cerebral attack);
• if you have mild to moderate low blood pressure;
• if you have uncontrolled blood pressure, especially after a change in your antihypertensive treatment;
• if you have severe heart failure or heart failure with an ECG abnormality called "bundle branch block";
• if you have chronic retinal eye disease;
• if you have moderate liver problems;
• if you have severe kidney problems.

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

Children

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

Taking Ivabradina tablets with other medicines

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

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

• fluconazole (an antifungal medicine);
• rifampicin (an antibiotic);
• barbiturates (for sleep disorders or epilepsy);
• phenytoin (for epilepsy);
• Hypericum perforatum or St. John's wort (herbal remedy for depression);
• medicines that prolong the QT interval used to treat heart rhythm disorders or other conditions:
  • quinidine, disopyramide, ibutilide, sotalol, amiodarone (for treating heart rhythm disorders);
  • bepridil (for treating angina pectoris);
  • certain types of medicines for treating 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 (for gastroesophageal reflux).
• Certain types of diuretics that may reduce blood potassium levels, such as furosemide, hydrochlorothiazide, indapamide (used to treat edema, high blood pressure).

Taking Ivabradina tablets with food and drinks

Avoid grapefruit juice during treatment with Ivabradina tablets.

Pregnancy and breastfeeding

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

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

Do not take Ivabradina tablets if you are of childbearing age unless you are using reliable contraceptive methods (see "Do not take Ivabradina tablets").

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

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

Driving and using machines

Ivabradina tablets may cause transient luminous visual phenomena (a brief brightness in the visual field, see "Possible side effects"). If this occurs,

take care when driving or using machinery in situations where sudden changes in light intensity may occur, especially when driving at night.

3. How to take Ivabradine Combix tablets

Follow exactly the instructions for use of this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Ivabradine tablets should be taken with breakfast and dinner.

If you are being treated for stable angina

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

If you are being treated for chronic heart failure

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

If you take more Ivabradine tablets than you should

An overdose of ivabradine tablets may make you feel tired or short of breath due to your heart beating too slowly. If this happens, contact your doctor immediately.

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

If you forget to take Ivabradine tablets

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

If you stop taking Ivabradine tablets

Treatment for stable angina or chronic heart failure is usually lifelong; therefore, you must consult your doctor before stopping this medicine.

If you think that the effect of ivabradine tablets is too strong or too weak, inform your doctor or pharmacist.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The frequency of the possible adverse 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 adverse reactions with this medicine are dose-dependent and are related to its mechanism of action:

Very common:

Luminous visual phenomena (brief moments of increased brightness, almost always caused by sudden changes in light intensity). These may also be described as halos, colored flashes, image fragmentation, or multiple images. These usually appear during the first two months of treatment, after which they may recur repeatedly and resolve during or after treatment.

Common:

Changes in heart function (symptoms include slowing of the heart rate). This occurs especially during the first 2 to 3 months after starting treatment.

Other adverse effects that have been reported include:

Common:

Rapid irregular heartbeat, sensation of abnormal heartbeat, uncontrolled blood pressure, headache, dizziness, and blurred vision (cloudy vision).

Uncommon:

Palpitations and extra heartbeats, sensation of dizziness (nausea), constipation, diarrhoea, abdominal pain, sensation of spinning (vertigo), difficulty breathing (dyspnoea), muscle cramps, changes in laboratory tests: elevated blood levels of uric acid, excess eosinophils (a type of white blood cell), and elevated 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 electrocardiogram, double vision, visual disturbance.

Rare:

Urticaria, itching, skin redness, malaise.

Very rare:

Irregular heartbeats.

Reporting of adverse effects

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

5. Storage of Ivadradina Combix tablets

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their packaging at a SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Ivabradina Combix

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

Tablet core: Lactose, microcrystalline cellulose (460i), magnesium stearate (470b), pregelatinized corn starch (1500 LM), sodium starch glycolate from potato type A, colloidal anhydrous silica.

Coating: Opadry Beige 03G570000.

Appearance of the product and contents of the container

Film-coated tablets, light brown in color, round-shaped, marked with the number “2” on one side and smooth on the other.

Ivabradina Combix 7.5 mg is available in blisters, in pack sizes 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 the most recent review of this leaflet: January 2017

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/