Ivabradine tablet is indicated for the symptomatic treatment of chronic stable angina pectoris in patients with coronary artery disease and normal sinus rhythm. It is used:

• In patients who are unable to tolerate or have a contraindication to the use of beta-blockers; OR
• In combination with beta-blockers in patients whose condition is inadequately controlled with an optimal beta-blocker dose and whose heart rate is >60 bpm.

Ivabradine is a selective heart rate–reducing agent. It works by specifically inhibiting the cardiac pacemaker If current, which controls spontaneous diastolic depolarization in the sinus node and regulates heart rate. By lowering heart rate, ivabradine reduces cardiac workload and oxygen demand. It also prolongs diastole, improving coronary artery perfusion and increasing oxygen supply to the heart. Its effects are limited to the sinus node and do not influence intra-atrial, atrioventricular, or intraventricular conduction, myocardial contractility, or ventricular repolarization.

Adult: The usual recommended starting dose of Ivabradine is 5 mg twice daily which may be increased after 3–4 weeks of treatment to 7.5 mg twice daily, depending on therapeutic response. Usual dose is 1 tablet in the morning and 1 tablet in the evening during meals. If the heart rate decreases persistently below 50 bpm at rest or if symptoms related to bradycardia, the dose must be adjusted downwards to 2.5 mg twice daily (one half of the 5 mg tablet twice daily). Treatment must be discontinued if heart rate remains below 50 bpm or symptoms of bradycardia persist.

Elderly: Since ivabradine has been studied in a limited number of patients aged 75 years or more, a lower starting dose should be considered for these patients (2.5 mg twice daily i.e. one half 5 mg tablet twice daily) before up-titration if necessary.

Renal insufficiency: No dose adjustment is required in patients with renal insufficiency and creatinine clearance above 15 ml/min. No data are available in patients with creatinine clearance below 15 ml/min. Ivabradine should therefore be used with precaution in this population.

Hepatic impairment: No dose adjustment is required in patients with mild hepatic impairment. Caution should be exercised when using ivabradine in patients with moderate hepatic impairment. Ivabradine is contra-indicated for use in patients with severe hepatic insufficiency.

Children and adolescents: Ivabradine is not recommended for use in children and adolescents due to a lack of data on safety and efficacy.

Use of QT interval–prolonging medicines is not recommended with ivabradine. These include cardiovascular agents (e.g., quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone) and non-cardiovascular agents (e.g., pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, intravenous erythromycin). Concomitant use should be avoided because QT prolongation may worsen due to reduced heart rate. If combination is unavoidable, careful cardiac monitoring is required.

Ivabradine is contraindicated in patients with hypersensitivity to ivabradine or any excipients, resting heart rate below 60 bpm before treatment, cardiogenic shock, acute myocardial infarction, severe hypotension (<90/50 mmHg), severe hepatic impairment, sick sinus syndrome, sino-atrial block, pacemaker dependence, unstable angina, third-degree AV block, and when used with strong CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics, HIV protease inhibitors).

Common adverse effects include visual disturbances, blurred vision, bradycardia, first-degree AV block, ventricular extrasystoles, headache, and dizziness.

Animal studies in rats have shown no adverse effects on fertility in both males and females. However, there is limited or no adequate data on the use of ivabradine in pregnant women. Therefore, ivabradine is contraindicated during pregnancy. Animal studies also indicate that ivabradine is excreted in breast milk; hence, its use is contraindicated during breastfeeding.

Use with caution in patients with mild to moderate hypotension, atrial fibrillation, congenital QT syndrome, or those receiving QT-prolonging medications. Also use cautiously in patients with moderate hepatic impairment or severe renal impairment.

Other Anti-anginal and Anti-ischemic drugs

Store below 30°C, protected from light and moisture. Keep out of reach of children.