Leaflet: information for the patient

Ivabradina Combix 5 mg film-coated tablets

Read 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. Do not give it to others even if they have similar symptoms to you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

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

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

3. How to take Ivabradina Combix tablets

4. Possible side effects

5. Storage of Ivabradina Combix tablets

6. Contents of the pack and additional information

Ivabradina is a heart medication that serves to treat:

• Stable angina pectoris (causing chest pain) in adult patients whose heart rate is 70 beats per minute or higher. It is used in adult patients who cannot tolerate or take heart medications called beta-blockers. It is also used in association with beta-blockers in adult patients whose condition is not fully controlled with a beta-blocker.
• Chronic heart failure in adult patients whose heart rate is 75 beats per minute or higher. It is used in association with standard treatment, including treatment with beta-blockers or when beta-blockers are contraindicated or not tolerated.

About stable angina (usually known as “angina”)

Stable angina 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 common symptom of angina is chest pain or discomfort. Angina is more likely to appear 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 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 your body. The most common symptoms of heart failure are difficulty breathing, fatigue, tiredness, and swelling of the ankles.

How does Ivabradina work?

Ivabradina primarily acts by reducing the heart rate by a few 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.

In addition, as a high heart rate negatively affects the functioning of the

heart and the vital prognosis in patients with chronic heart failure, the specific action of lowering the heart rate of Ivabradina helps to improve the functioning of the heart and the vital prognosis in these patients.

Do not take Ivabradina tablets

• 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 are experiencing 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 where chest pain appears 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 antifungal medications (such as ketoconazole, itraconazole), macrolide antibiotics (such as josamycin, clarithromycin, telithromycin, or oral erythromycin), HIV infection treatments (such as nelfinavir, ritonavir), or nefazodone (a depression medication) or diltiazem, verapamil (used to treat high blood pressure or angina);
• if you are a fertile woman 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 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 electrocardiogram (ECG) anomaly called "prolonged QT syndrome",
• if you have symptoms such as fatigue, dizziness, or difficulty breathing (this may mean your heart is beating too slowly),
• if you have symptoms of atrial fibrillation (unusual resting pulse above 110 beats per minute or irregular, without apparent reason, that makes it difficult to measure),
• if you have had a recent stroke (cerebral attack),
• if you have mild to moderate low blood pressure,
• if you have uncontrolled high blood pressure, especially after a change in your antihypertensive treatment,
• if you have severe heart failure or heart failure with an ECG anomaly called "branch block",
• if you have chronic retinal disease of the eye,
• if you have moderate liver problems,
• if you have severe kidney problems.

If you meet any of these conditions, 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 old.

Use of Ivabradina tablets with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may take any other medicine.

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

• fluconazole (an antifungal medication)
• rifampicin (an antibiotic)
• barbiturates (for sleep problems or epilepsy)
• phenytoin (for epilepsy)
• Hypericum perforatum or St. John's Wort (a medicinal plant for depression treatment).
• Medicines that prolong the QT interval to treat heart rhythm disorders or other alterations:
• • quinidine, disopyramide, ibutilide, sotalol, amiodarone (for heart rhythm disorders)
  • bepridil (for angina treatment)
  • certain types of medications for anxiety, schizophrenia, or other psychoses (such as pimozide, ziprasidone, sertindole)
  • antimalarial medications (such as mefloquine or halofantrine)
  • intravenous erythromycin (an antibiotic)
  • pentamidine (an antiparasitic medication)
  • cisapride (for gastroesophageal reflux).
• Some types of diuretics that may cause a reduction in 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 intend 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 fertile and do not use 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 intend to start breastfeeding, as you should stop breastfeeding if you are taking Ivabradina tablets.

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

Driving and operating machinery

Ivabradina tablets may cause transient visual phenomena (a

fleeting luminosity in the field of vision, see "Possible side effects"). If this happens,

be careful when driving or using machinery in situations where there may be sudden changes in light intensity, especially when driving at night.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Ivabradina tablets should be taken with breakfast and dinner.

If you are being treated for stable angina

The initial dose should not exceed one Ivabradina 5 mg tablet twice a day. If you still have angina symptoms and have tolerated the 5 mg dose twice a day, the dose can 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 at night. 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 at night.

If you are being treated for chronic heart failure

The recommended initial normal dose is one 5 mg Ivabradina tablet twice a day, increasing if necessary to one 7.5 mg Ivabradina tablet twice a day. Your doctor will decide on the suitable dose for you. The usual dose is one tablet in the morning and one tablet at night. In some cases (for example, if you are an elderly person), 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 at night.

If you take more Ivabradina tablets than you should

A high dose of Ivabradina tablets can make you feel tired or have difficulty breathing due to your heart 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 Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take Ivabradina tablets

If you forgot to take a dose of Ivabradina tablets, take the next dose at the scheduled time. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Ivabradina tablets

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

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

If you have any other questions about the use of this medication, ask your doctor or

pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience 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: the frequency cannot be estimated from the available data.

The most frequent adverse reactions with this medicine are dose-dependent and related to its mechanism of action:

Very common:

Phenomena of luminous vision (brief moments of increased luminosity, caused almost always by sudden changes in light intensity). They can also be described as a halo, flashes of color, image decomposition, or multiple images. These generally 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 heart rate). This occurs especially in the first 2 to 3 months after starting treatment.

Other adverse reactions have also been reported:

Common:

Irregular rapid heart contractions, abnormal heart palpitations, uncontrolled blood pressure, headache, dizziness, and blurred vision (hazy vision).

Uncommon:

Palpitations and additional heartbeats, sensation of dizziness (nausea), constipation, diarrhea, abdominal pain, sensation of spinning (vertigo), difficulty breathing (dyspnea), muscle cramps, changes in laboratory tests: elevated blood levels of uric acid, an excess of eosinophils (a type of white blood cell), and elevated blood levels of creatinine (a muscle degradation product), skin rash, angioedema (inflammation 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 alteration.

Rare:

Urticaria, itching, skin redness, indisposition.

Very rare:

Irregular heartbeats.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also

report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.By reporting

side effects, you can contribute to providing more information on the safety of

this medicine.

Keepthis medicationout of sight and reach of children.

Do not usethis medicationafter the expiration date that appears onthe packaging after CAD.The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or trash. Dispose of packaging and medications you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Ivabradina Combix

• The active ingredient is ivabradina. Each film-coated tablet contains 5 mg of ivabradina
• The other components are:

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

Coating: Opadry Beige 03G570000.

Appearance of the product and content of the container

Film-coated tablets, brownish yellow in color, oblong, with a notch on both sides with the mark “?” on one face and smooth on the other.

The tablet can be divided into equal doses.

Ivabradina Combix 5 mg is presented in blisters in containers of 56 tablets.

Holder of the marketing authorization

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

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

Last review date of this leaflet:January 2017

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