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Ivabradine

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Ivabradine, Corlanor

  • See Also
  1. Systolic Dysfunction
  • Indications
  1. Refractory, persistent CHF symptoms
    1. Consider as an adjunct to maximal medical therapy (e.g. ACE Inhibitor, Beta Blocker and Aldosterone Antagonist)
    2. Requires stable patients in sinus rhythm with Heart Rate >70, EF <35%
    3. Very expensive tertiary adjunct ($430/month) in CHF
  • 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
  2. Food delays absorption
  • Dosing
  • Adults
  1. Start at 5 mg orally twice daily
    1. Start at 2.5 mg orally twice daily if risk of Hypotension with Bradycardia, or conduction defect
  2. Titrate starting after 2 weeks
    1. Increase to 7.5 mg twice daily after 2 weeks if Heart Rate >60/min
    2. 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. Third degree AV Block or Sick Sinus Syndrome
  4. Visual Field increased brightness (2%)
  5. 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 (Teratogenic)
  2. Unsafe in Lactation
  • References
  1. (2015) Presc Lett 22(6): 31
  2. (2017) Presc Lett 24(7)
  3. Davis (2016) Am Fam Physician 93(8): 683-4 [PubMed]
  4. Swedberg (2010) Lancet 376(9744):875-85 +PMID:20801500 [PubMed]