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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/594714/2015

EMEA/H/C/004187

EPAR summary for the public

Ivabradine Anpharm

ivabradine

This is a summary of the European public assessment report (EPAR) for Ivabradine Anpharm. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Ivabradine Anpharm.

For practical information about using Ivabradine Anpharm, patients should read the package leaflet or contact their doctor or pharmacist.

What is Ivabradine Anpharm and what is it used for?

Ivabradine Anpharm is a medicine used to treat the symptoms of long-term stable angina (pains to the chest, jaw and back, brought on by physical effort) in adults with coronary artery disease (disease of the heart caused by the obstruction of the blood vessels that supply blood to the heart muscle). The medicine is used in patients who have a normal heart rhythm but whose heart rate is at least 70 beats per minute. It is used in patients who cannot be treated with beta-blockers (another type of medicine to treat angina) or in combination with a beta blocker in patients whose disease is not controlled by beta blockers alone.

Ivabradine Anpharm is also used in patients with long-term heart failure (when the heart cannot pump enough blood to the rest of the body) who have a normal heart rhythm but whose heart rate is at least 75 beats per minute. It is used in combination with standard therapy including beta-blockers, or in patients who cannot be treated with beta-blockers.

This medicine is the same as Procoralan, which is already authorised in the EU. The company that makes Procoralan has agreed that its scientific data can be used for Ivabradine Anpharm ('informed consent').

Ivabradine Anpharm contains the active substance ivabradine.

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© European Medicines Agency, 2015. Reproduction is authorised provided the source is acknowledged.

How is Ivabradine Anpharm used?

Ivabradine Anpharm is available as tablets (5 and 7.5 mg) and can only be obtained with a prescription. The recommended starting dose is 5 mg twice a day with meals, which the doctor may increase to 7.5 mg twice a day or decrease to 2.5 mg (half a 5-mg tablet) twice a day depending on the patient's heart rate and symptoms. In patients over 75 years old, a lower starting dose of 2.5 mg twice a day can be used. Treatment must be stopped if the heart rate decreases persistently below 50 beats per minute or if symptoms of bradycardia (slow heart rate) continue. When used for angina, treatment should be stopped if there is no improvement in symptoms after 3 months and the doctor should consider stopping treatment if the improvement in symptoms or the reduction in the heart rate is only limited.

For further information see the summary of product characteristics (also part of the EPAR).

How does Ivabradine Anpharm work?

The symptoms of angina are caused by the heart not receiving enough oxygenated blood. In stable angina, these symptoms appear during physical effort. The active substance in Ivabradine Anpharm, ivabradine, works by blocking the 'I_f currents' in the sinus node, the natural 'pacemaker' that controls the heart's contractions and regulates the heart rate. When these currents are blocked, the heart rate is lowered, so that the heart has less work to do and needs less oxygenated blood. Ivabradine Anpharm therefore reduces or prevents the symptoms of angina.

The symptoms of heart failure are caused by the heart not pumping enough blood around the body. By lowering the heart rate, Ivabradine Anpharm reduces the stress on the heart, thereby slowing the progression of heart failure and improving symptoms.

What benefits of Ivabradine Anpharm have been shown in studies?

Ivabradine Anpharm has been studied in five main studies involving over 4,000 adults with long-term stable angina. The medicine was compared with placebo (a dummy treatment) in 360 patients, atenolol (a beta-blocker) in 939 patients and amlodipine (another medicine used to treat angina) in 1,195 patients. It was also compared with placebo as an add-on to atenolol in 889 patients and as an add-on to amlodipine in 728 patients. Each study lasted three to four months. The main measure of effectiveness was how long the patients could exercise on a bicycle or a treadmill, measured at the start and the end of each study. The studies showed that the medicine was more effective than placebo at improving exercise capacity and was as effective as atenolol and amlodipine. Ivabradine Anpharm was also more effective than placebo when added to atenolol. However, adding it to amlodipine did not provide an additional benefit.

Ivabradine Anpharm has also been compared with placebo in one main study involving 6,558 patients with long-term moderate to severe heart failure. The main measure of effectiveness was the time until death due to disease of the heart or blood vessels, or hospitalisation due to worsening heart failure. It was more effective than placebo at preventing death due to disease of the heart or blood vessels or hospitalisation due to worsening heart failure: 24.5% (793 out of 3,241) of patients treated with Ivabradine Anpharm died or were hospitalised for the first time due to worsening heart failure, compared with 28.7% (937 out of 3,264) of patients treated with placebo.

Another study compared Ivabradine Anpharm with placebo in 19,102 patients with coronary heart disease and without clinical heart failure. The main measure of effectiveness was a reduction in the risk of death due to heart problems and non-fatal heart attack. In this study a specific subgroup of patients who had symptomatic angina had a small but significant increase in the combined risk of cardiovascular death or non-fatal heart attack with Ivabradine Anpharm compared with placebo (3.4% vs 2.9% yearly incidence rates). However it should be noted that patients in this study were given doses higher than the recommended dose (up to 10 mg twice a day).

What are the risks associated with Ivabradine Anpharm?

The most common side effect with Ivabradine Anpharm (seen in more than 1 patient in 10) is luminous phenomena or 'phosphenes' (a temporary brightness in the field of vision). For the full list of all side effects reported with Ivabradine Anpharm, see the package leaflet.

Ivabradine Anpharm must not be used in patients who have a resting heart rate below 70 beats per minute, very low blood pressure, various types of heart disorder (including cardiogenic shock, rhythm disorders, heart attack, unstable or acute (sudden) heart failure and unstable angina) or severe liver problems. It must not be used in women who are pregnant, breastfeeding or by women who could become pregnant and who are not using appropriate contraceptives. Caution is needed if Ivabradine Anpharm is taken with some other medicines. For the full list of restrictions, see the package leaflet.

Why is Ivabradine Anpharm approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that Ivabradine Anpharm was shown to be effective in long-term angina with an acceptable safety profile for it to provide an alternative treatment for patients who cannot take beta-blockers or whose disease is not controlled with them. It also concluded that Ivabradine Anpharm was effective in long-term heart failure with an acceptable safety profile. The Committee decided that Ivabradine Anpharm's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Ivabradine Anpharm?

A risk management plan has been developed to ensure that Ivabradine Anpharm is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Ivabradine Anpharm, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Ivabradine Anpharm must carry out a further study of the patients using the medicine and the way that it is used, and of how well measures to reduce the risks of treatment are being followed.

Further information can be found in the summary of the risk management plan.

Other information about Ivabradine Anpharm

The European Commission granted a marketing authorisation valid throughout the European Union for Ivabradine Anpharm on 8 September 2015.

The full EPAR and risk management plan summary for Ivabradine Anpharm can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more information about treatment with Ivabradine Anpharm, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 09-2015.

Ivabradine Anpharm

EMA/594714/2015

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