What is the side effect profile of Ivabradine (Corlanor)?

Ivabradine Side Effect Profile

Ivabradine has a generally well-tolerated side effect profile with the most common adverse effects being visual phosphenes (brightness phenomena) and bradycardia, which are typically mild to moderate and often transient. 1

Common Side Effects

Cardiovascular Effects

• Bradycardia: Occurs in approximately 10% of patients (vs 2.2% with placebo) 1, 2
  • Usually dose-dependent and proportional to baseline heart rate
  • Rarely severe enough to require discontinuation (<1% of patients) 3, 4
• Hypertension/increased blood pressure: 8.9% (vs 7.8% with placebo) 1
• Atrial fibrillation: 8.3% (vs 6.6% with placebo) 1

Visual Effects

• Phosphenes (visual brightness phenomena): 2.8-3% of patients (vs 0.5% with placebo) 1, 5, 2
  • Described as transiently enhanced brightness in a limited area of visual field
  • May include halos, image decomposition (stroboscopic/kaleidoscopic effects), colored bright lights
  • Usually triggered by sudden variations in light intensity
  • Typically occur within first 2 months of treatment
  • Generally mild to moderate in intensity
  • Rarely lead to treatment discontinuation (<1% of patients)
  • Often resolve during or after treatment 1

Less Common Side Effects

• Syncope 1
• Hypotension 1
• Serious cardiac arrhythmias (rare):
  • Torsade de pointes
  • Ventricular fibrillation
  • Ventricular tachycardia 1
• Dermatological reactions:
  • Angioedema
  • Erythema
  • Rash
  • Pruritus
  • Urticaria 1
• Other visual disturbances:
  • Vertigo
  • Diplopia
  • Visual impairment 1

Safety Considerations and Precautions

Contraindications

• Recent worsening of heart failure symptoms
• Very low blood pressure (hypotension)
• Certain heart conditions:
  • Sick sinus syndrome
  • Sinoatrial block
  • 3rd degree atrioventricular block
• Pre-existing slow resting heart rate
• Certain liver problems
• Concurrent use of medications that increase ivabradine effects 1

Drug Interactions

• Avoid concurrent use with:
  • Other medications that lower heart rate (beta blockers, calcium channel blockers)
  • QT-prolonging medications
  • Grapefruit juice
  • St. John's wort 1, 4

Monitoring Recommendations

• Regular heart rate monitoring, especially during dose titration
• Monitor for symptoms of bradycardia (dizziness, fatigue, lack of energy)
• In children, watch for signs of bradycardia including poor feeding, difficulty breathing, or cyanosis 1
• Consider baseline ECG before starting therapy in high-risk patients 6

Special Populations

Pediatric Patients

• Limited data available
• In children with postural orthostatic tachycardia syndrome (POTS), ivabradine appears to be well-tolerated
• Phosphenes reported in approximately 4.5% of pediatric patients 7

Elderly and Patients with Comorbidities

• May have increased risk of bradycardia
• Consider starting at lower doses and titrating slowly 6

Mechanism of Side Effects

Ivabradine's side effects are largely related to its mechanism of action:

• Bradycardia: Results from selective inhibition of the I(f) current in sinoatrial node cells 3, 4
• Visual effects: Caused by inhibition of retinal h-channels that carry the I(h) current (similar to I(f) current) 3, 4

The drug does not cross the blood-brain barrier, so CNS effects are minimal 3, 4. Unlike other rate-controlling agents, ivabradine does not cause negative inotropic effects or vasoconstriction 4.