CORALAN

What it is

Coralan contains ivabradine (as hydrochloride) and is available as film-coated tablets in 5 mg and 7.5 mg strengths. Ivabradine is a heart rate lowering agent, acting by selective inhibition of the cardiac pacemaker If current that controls the spontaneous diastolic depolarisation in the sinus node and regulates heart rate.

Approved indications

— Symptomatic treatment of chronic stable angina due to atherosclerotic coronary artery disease in patients with normal sinus rhythm and heart rate at or above 70 bpm, who are unable to tolerate or have a contraindication to the use of beta-blockers, or in combination with atenolol 50 mg once daily when angina is inadequately controlled. — Treatment of symptomatic chronic heart failure of NYHA Classes II or III and with documented left ventricular ejection fraction (LVEF) ≤ 35% in adult patients in sinus rhythm and with heart rate at or above 77 bpm, in combination with optimal standard chronic heart failure treatment.

Dosing overview

In patients aged 75 years or more, a lower starting dose (2.5 mg twice daily) should be considered before up-titration if necessary. Ivabradine should be taken once in the morning and once in the evening during meals.

Key safety warnings

Ivabradine is indicated only for symptomatic treatment of chronic stable angina because it has no benefits on cardiovascular outcomes such as myocardial infarction or cardiovascular death. Ivabradine must not be initiated in patients with a pre-treatment resting heart rate below 70 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, and if heart rate remains below 50 bpm or symptoms persist, treatment should be discontinued. In patients treated with ivabradine the risk of developing atrial fibrillation is increased. It is recommended to regularly monitor ivabradine-treated patients for the occurrence of atrial fibrillation (sustained or paroxysmal), including ECG monitoring if clinically indicated, and patients should be informed of signs and symptoms of atrial fibrillation and be advised to contact their physician if these occur. The use of ivabradine in patients with QT prolongation, congenital QT syndrome or treated with QT prolonging medicinal products should be avoided; if the combination appears necessary, close cardiac monitoring is needed, as heart rate reduction with ivabradine may exacerbate QT prolongation, which may give rise to severe arrhythmias in particular Torsade de pointes. Ivabradine may cause transient luminous phenomena consisting mainly of phosphenes, and the possible occurrence of such luminous phenomena should be taken into account when driving or using machines in situations where sudden variations in light intensity may occur, especially when driving at night.

Contraindications

Coralan is contraindicated in patients with known hypersensitivity to ivabradine or any of the excipients, in conditions in which the sinus node is no longer the cardiac pacemaker (such as artificial pacemaker or sick sinus syndrome), third degree atrioventricular (AV) block, unstable or acute heart failure, resting heart rate below 70 bpm prior to treatment, severe hypotension (< 90/50 mmHg), unstable angina, cardiogenic shock, acute myocardial infarction, and sino-atrial block. Coralan is also contraindicated in patients with Hypertrophic Cardiomyopathy (HOCM) unless co-existing Coronary Artery Disease (CAD) is proven, in combination with potent cytochrome P450 3A4 (CYP 3A4) inhibitors such as ketoconazole, macrolide antibiotics, cyclosporin, gestodene and anti-retroviral drugs, and in combination with verapamil or diltiazem which are moderate CYP3A4 inhibitors with heart rate reducing properties. Coralan is contraindicated in severe hepatic insufficiency, during pregnancy, lactation, and in women of childbearing potential not using appropriate contraceptive measures.

PBS listing

Coralan 5 mg and 7.5 mg tablets are listed on the PBS with streamlined restriction, with an ex-manufacturer price of A$31.03 per pack, with 2 PBS items for each strength.

Regulatory history

Coralan ivabradine 5 mg and 7.5 mg tablets were first listed on the ARTG on 31 October 2006. On 9 July 2012, the TGA approved Coralan for the treatment of symptomatic chronic heart failure of NYHA Classes II or III with documented left ventricular ejection fraction ≤ 35% in adult patients in sinus rhythm and with heart rate at or above 77 bpm when used in combination with optimal standard chronic heart failure treatment. The TGA's evaluation focused on the pivotal SHIFT study, which demonstrated the superiority of ivabradine over placebo in reducing cardiovascular mortality or hospitalisation for worsening heart failure in patients with symptomatic chronic heart failure and reduced left ventricular ejection fraction.