CORALAN

Symptomatic treatment of chronic stable angina

Ivabradine is indicated in the symptomatic treatment of chronic stable angina in coronary adults in sinus rhythm with a heart rate greater than or equal to 70 bpm.

Ivabradine is indicated:

· in adults with intolerance or a contraindication to beta-blockers,

· or in association with beta-blockers in patients insufficiently controlled by an optimal dose of beta-blockers.

Treatment of chronic heart failure

Ivabradine is indicated in the treatment of chronic heart failure NYHA class II to IV with systolic dysfunction, in patients in sinus rhythm with a heart rate greater than or equal to 75 bpm, in association with standard treatment including beta-blockers, or in case of contraindication or intolerance to beta-blockers (see section 5.1).

Women of childbearing age

Women of childbearing age must use an effective method of contraception throughout their treatment (see section 4.3).

Pregnancy

There is no data or limited data on the use of ivabradine in pregnant women. Studies conducted in animals have shown reproductive toxicity. These studies have shown embryotoxic and teratogenic effects (see section 5.3). The potential risk in humans is unknown. Therefore, ivabradine is contraindicated during pregnancy (see section 4.3).

Breastfeeding

Animal studies show that ivabradine is excreted in breast milk. Therefore, ivabradine is contraindicated during breastfeeding (see section 4.3). Women who must be treated with ivabradine should discontinue breastfeeding and choose another method of feeding for their child.

Fertility

Studies in rats have shown that there is no effect on the fertility of males and females (see section 5.3).

A specific study intended to evaluate the influence of ivabradine on driving was conducted in healthy volunteers; no alteration in driving was demonstrated.

Nevertheless, based on post-MAA data, cases of impairment of the ability to drive vehicles due to visual symptoms have been reported. Ivabradine may be responsible for transient luminous phenomena, mainly of the type of phosphenes (see section 4.8). The possible appearance of such luminous phenomena must be taken into account when driving vehicles or using machines in situations where sudden changes in brightness are likely to occur, especially when driving at night.

Ivabradine has no influence on the ability to use machines.

Summary of the safety profile

Ivabradine has been studied in clinical trials involving approximately 45 000 patients. The most frequent adverse reactions observed with ivabradine, luminous phenomena (phosphenes) and bradycardia, are dose-dependent and related to the pharmacological effect of the medicinal product.

Table of adverse reactions

The following adverse reactions have been reported during clinical trials and are listed below using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).

*Event from spontaneous reporting: frequency calculated from clinical study data.

Description of certain adverse reactions

Luminous phenomena (phosphenes) were reported by 14,5 % of patients, described as a transiently increased brightness in a limited area of the visual field. They are usually triggered by sudden variations in light intensity. Phosphenes can be described as a halo, image decomposition (stroboscopic or kaleidoscopic effects), colored bright lights, or multiple images (retinal persistence). Phosphenes generally appear within the first two months of treatment, after which they may occur repeatedly. Phosphenes are generally described as mild to moderate in intensity. They most often resolve during or after treatment, with a majority (77,5 %) resolving during treatment. Less than 1 % of patients changed their daily habits or discontinued treatment due to phosphenes.

Bradycardia was reported by 3,3 % of patients, particularly during the first 2 or 3 months of treatment. 0,5 % of patients experienced severe bradycardia with a heart rate less than or equal to 40 bpm.

During the SIGNIFY study, atrial fibrillation was observed in 5,3 % of patients treated with ivabradine versus 3,8 % of patients in the placebo group. In an analysis pooling data from all phase II and III double-blind studies, with a duration of at least three months and including more than 40000 patients, an incidence of 4,86 % was observed for the occurrence of atrial fibrillation in patients treated with ivabradine compared to an incidence of 4,08 % in subjects in the control groups (HR 1,26 95% CI [1,15-1,39]).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse reaction via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and network of Regional Pharmacovigilance Centres - Website: www.signalement-sante.gouv.fr .