Pharm

Ivabradine

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Ivabradine, Corlanor

  • Indications
  1. Persistent CHF symptoms in stable patients in sinus rhythm with Heart Rate >70, EF <35
  2. Very expensive adjunct ($430/month) in CHF following ACE Inhibitor, Beta Blocker, Aldosterone Antagonist
  • Contraindications
  1. Severe Hepatic Impairment
  2. Sick Sinus Syndrome
  3. Sinoatrial Block
  4. Second or Third Degree Atrioventricular Block (without Pacemaker)
  5. Resting Heart Rate <60 beats per minute
  6. Pacemaker dependence
  • Mechanism
  1. Hyperpolarization-activated cyclic nucleotide-gated channel blocker
  2. Decreases Heart Rate without affecting myocardial contractility
    1. Does not cause Hypotension
  • Pharmacokinetics
  1. CYP3A4 metabolized
  • Dose
  1. Start at 5 mg twice daily
  2. Increase to 7.5 mg twice daily after 2 weeks if Heart Rate >60/min
  3. Decrease to 2.5 mg twice daily after 2 weeks if Heart Rate <50/min
  • Adverse effects
  1. Bradycardia (8-13%)
    1. Risk factors
      1. Combined with Beta Blockers, Amiodarone, Digoxin, Diltiazem
      2. Cardiac conduction disorders
      3. Low resting Heart Rate
    2. Monitor carefully while titrating dose
    3. Avoid in patients with resting Heart Rate <70/min
  2. Atrial Fibrillation (1%)
  3. Visual Field increased brightness (2%)
  4. Hypertension
  • Efficacy
  1. Prevents CHF hospitalizations (NNT 25)
  2. Does not reduce mortality
  3. Swedberg (2010) Lancet 376(9744): 875-85 [PubMed]
  • Drug Interactions
  1. Strong CYP3A4 inhibitors potentiate Ivabradine
    1. Verapamil (also increases Bradycardia risk)
    2. Diltiazem (also increases Bradycardia risk)
    3. Macrolide Antibiotics
    4. Protease Inhibitors
  2. CYP3A4 Inducers reduce Ivabradine effect
    1. Rifampin
    2. Phenytoin (Dilantin)
  • Safety
  1. Pregnancy Category D