Carivalan Warnings

Special warnings: Lack of benefit on clinical outcomes in patients with symptomatic chronic stable angina pectoris: Carvedilol + Ivabradine (Carivalan) is indicated only for symptomatic treatment of chronic stable angina pectoris because ivabradine has no benefits on cardiovascular outcomes (e.g. myocardial infarction or cardiovascular death).
Measurement of heart rate: Given that the heart rate may fluctuate considerably over time, serial heart rate measurements, ECG or ambulatory 24-hour monitoring should be considered when determining resting heart rate in patients on treatment with ivabradine when titration is considered. This also applies to patients with a low heart rate, in particular when heart rate decreases below 50 bpm, or after dose reduction.
Cardiac 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). Carvedilol + Ivabradine (Carivalan) is therefore not recommended in patients with atrial fibrillation or other cardiac arrhythmias that interfere with sinus node function.
In patients treated with ivabradine, the risk of developing atrial fibrillation is increased. Atrial fibrillation has been more common in patients using concomitantly amiodarone or potent class I anti-arrhythmics. 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).
Patients should be informed of signs and symptoms of atrial fibrillation and be advised to contact their physician if these occur. If atrial fibrillation develops during treatment, the balance of benefits and risks of continued Carvedilol + Ivabradine (Carivalan) treatment should be carefully reconsidered.
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 a low heart rate: Carvedilol + Ivabradine (Carivalan) must not be initiated in patients with a pre-treatment resting heart rate below 50 beats per minute.
If, during treatment with Carvedilol + Ivabradine (Carivalan), resting heart rate decreases persistently below 50 bpm or the patient experiences symptoms related to bradycardia such as dizziness, fatigue or hypotension, down titration should be done with the individual components ensuring the patient is maintained at an optimal dose of carvedilol and ivabradine or treatment discontinued.
Combination with calcium channel blockers: Concomitant use of Carvedilol + Ivabradine (Carivalan) with heart rate reducing calcium channel blockers such as verapamil or diltiazem is contraindicated. 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 Carvedilol + Ivabradine (Carivalan) treatment. Carvedilol + Ivabradine (Carivalan) is not recommended in heart failure patients with NYHA functional classification IV due to limited amount of data with ivabradine in this population.
Carvedilol + Ivabradine (Carivalan) should be used with caution in combination with digitalis glycosides since these products, as well as carvedilol, may slow the AV conduction.
Stroke: The use of Carvedilol + Ivabradine (Carivalan) is not recommended immediately after a stroke since no data with ivabradine is available in these situations.
Visual function: Ivabradine influences retinal function. There is no evidence of a toxic effect of long-term ivabradine treatment on the retina. Cessation of treatment should be considered if any unexpected deterioration in visual function occurs. Caution should be exercised in patients with retinitis pigmentosa.