Ivabradine

Ivabradine is a pure heart rate lowering agent that acts by selective and specific inhibition of the cardiac pacemaker If current that controls the spontaneous diastolic depolarization in the sinus node and regulates heart rate. By decreasing heart rate, Ivabradine decreases the cardiac workload and oxygen consumption. Concomitantly, it prolongs diastole allowing increased perfusion of coronary arteries and increased oxygen supply to the heart.

• Symptomatic treatment of chronic stable angina pectoris (in coronary artery disease patients with normal sinus rhythm)

Adult Dose (Oral):

• Initial: 5 mg twice daily (with meals)
• May be increased after 3-4 weeks to 7.5 mg twice daily, depending on therapeutic response
• 1 tablet in the morning and 1 tablet in the evening during meals
• Heart rate <50 bpm: Reduce dose to 2.5 mg twice daily; if persists, discontinue
• Elderly (≥75 years): Initial: 2.5 mg twice daily

Renal Dose: CrCl >15 mL/min: No dose adjustment; CrCl <15 mL/min: Caution required

Hepatic Impairment: Mild: No dose adjustment; Moderate: Caution; Severe: Contraindicated

Child Dose: Not recommended

Common Side Effects:

• Slow heart rate (bradycardia)
• Headache
• Luminous phenomena (Enhanced brightness)
• High blood pressure
• Visual symptoms (blurred vision)
• 1st degree AV block
• Ventricular extrasystoles
• Dizziness

Precautions:

• Ivabradine may affect your ability to drive (transient luminous phenomena including phosphenes, especially when driving at night)
• May cause dizziness or sleepiness; do not drive or do anything requiring concentration until you know how it affects you
• Temporary changes in vision (enhanced visual brightness) may occur within first 2 months of treatment, gradually resolve
• Monitor blood pressure (may increase)
• Monitor heart rate (low heart rate is common side effect)
• Caution in mild to moderate hypotension, atrial fibrillation, QT syndrome patients

Contraindications:

• Pregnancy
• Lactation
• Resting heart rate <60 bpm before treatment
• Cardiogenic shock
• Acute myocardial infarction
• Severe hypotension (<90/50 mmHg)
• Severe hepatic insufficiency
• Sick sinus syndrome, sino-atrial block
• Heart failure (NYHA class III-IV)
• Pacemaker dependent
• Unstable angina, 3rd degree AV-block
• Concurrent use with potent CYP3A4 inhibitors

Drug Interactions:

• Concomitant use with QT-prolonging drugs is not recommended
• Concentrations may increase with CYP3A4 inhibitors
• Use with verapamil or diltiazem is not recommended
• Potentially Fatal: Concurrent use with potent CYP3A4 inhibitors is contraindicated

Food Interactions: It is not known whether it is safe to consume alcohol with Ivabradine; consult your doctor.

Use in Pregnancy: Unsafe during pregnancy; definite evidence of risk to developing baby; contraindicated in pregnancy.

Use in Lactation: Information regarding use during breastfeeding is not available; contraindicated in lactation; animal studies indicate excretion in milk.

Renal Impairment: CrCl >15 mL/min: No dose adjustment; CrCl <15 mL/min: Caution required; caution in severe kidney disease.

Hepatic Impairment: Mild: No dose adjustment; Moderate: Caution; Severe: Contraindicated; not recommended in severe liver disease.

Overdose: Severe bradycardia may occur; symptomatic supportive treatment; for symptomatic bradycardia, consider IV atropine or pacing.