Special warningsCardiac arrhythmias
Ivabradine is not effective in the treatment or prevention of cardiac arrhythmias and likely loses its efficacy when a tachyarrhythmia occurs (eg. ventricular or supraventricular tachycardia). Ivabradine is therefore not recommended in patients with atrial fibrillation or other cardiac arrhythmias that interfere with sinus node function.
It is recommended to regularly clinically monitor ivabradine treated patients for the occurrence of atrial fibrillation (sustained or paroxysmal), which should also include ECG monitoring if clinically indicated (e.g. in case of exacerbated angina, palpitations, irregular pulse). The risk of developing atrial fibrillation may be higher in chronic heart failure patients treated with ivabradine. Atrial fibrillation has been more common in patients using concomitantly amiodarone or potent class I anti-arrhythmics.
Chronic heart failure patients with intraventricular conduction defects (bundle branch block left, bundle branch block right) and ventricular dyssynchrony should be monitored closely.Use in patients with AV-block of 2nd degree
Ivabradine is not recommended in patients with AV-block of 2nd degree.Use in patients with a low heart rate
Ivabradine must not be initiated in patients with a pre-treatment resting heart rate below 60 beats per minute
If, during treatment, resting heart rate decreases persistently below 50 bpm or the patient experiences symptoms related to bradycardia such as dizziness, fatigue or hypotension, the dose must be titrated downward or treatment discontinued if heart rate below 50 bpm or symptoms of bradycardia persist .
Combination with calcium channel blockers
Concomitant use of ivabradine with heart rate reducing calcium channel blockers such as verapamil or diltiazem is not recommended . No safety issue has been raised on the combination of ivabradine with nitrates and dihydropyridine calcium channel blockers such as amlodipine. Additional efficacy of ivabradine in combination with dihydropyridine calcium channel blockers has not been established Chronic heart failure
Heart failure must be stable before considering ivabradine treatment. Ivabradine should be used with caution in heart failure patients with NYHA functional classification IV due to limited amount of data in this population.Stroke
The use of ivabradine is not recommended immediately after a stroke since no data is available in these situations.Visual function
Ivabradine influences on retinal function . To date, there is no evidence of a toxic effect of ivabradine on the retina, but the effects of long-term ivabradine treatment beyond one year on retinal function are currently not known. Cessation of treatment should be considered if any unexpected deterioration in visual function occurs. Caution should be exercised in patients with retinitis pigmentosa.
Precautions for usePatients with hypotension
Limited data are available in patients with mild to moderate hypotension, and ivabradine should therefore be used with caution in these patients. Ivabradine is contra-indicated in patients with severe hypotension (blood pressure < 90/50 mmHg) .Atrial fibrillation - Cardiac arrhythmias
There is no evidence of risk of (excessive) bradycardia on return to sinus rhythm when pharmacological cardioversion is initiated in patients treated with ivabradine. However, in the absence of extensive data, non urgent DC-cardioversion should be considered 24 hours after the last dose of ivabradine.Use in patients with congenital QT syndrome or treated with QT prolonging medicinal products
The use of ivabradine in patients with congenital QT syndrome or treated with QT prolonging medicinal products should be avoided . If the combination appears necessary, close cardiac monitoring is needed.
Heart rate reduction, as caused by ivabradine, may exacerbate QT prolongation, which may give rise to severe arrhythmias, in particular Torsade de pointes.Hypertensive patients requiring blood pressure treatment modifications.
In the SHIFT trial more patients experienced episodes of increased blood pressure while treated with ivabradine (7.1%) compared to patients treated with placebo (6.1%). These episodes occurred most frequently shortly after blood pressure treatment was modified, were transient, and did not affect the treatment effect of ivabradine. When treatment modifications are made in chronic heart failure patients treated with ivabradine blood pressure should be monitored at an appropriate interval .Excipients
Since tablets contain lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.