II. Indications
- Refractory, persistent CHF symptoms
- Consider as an adjunct to maximal medical therapy (e.g. ACE Inhibitor, Beta Blocker and Aldosterone Antagonist)
- Requires stable patients in sinus rhythm with Heart Rate >70, EF <35%
- Very expensive tertiary adjunct ($430/month) in CHF
III. Contraindications
- Severe Hepatic Impairment
- Sick Sinus Syndrome
- Sinoatrial Block
- Second or Third Degree Atrioventricular Block (without Pacemaker)
- Resting Heart Rate <60 beats per minute
- Pacemaker dependence
IV. Mechanism
- Hyperpolarization-activated cyclic Nucleotide-gated channel blocker
- Decreases Heart Rate without affecting myocardial contractility
- Does not cause Hypotension
V. Pharmacokinetics
- CYP3A4 metabolized
- Food delays absorption
VI. Dosing: Adults
- Start at 5 mg orally twice daily
- Start at 2.5 mg orally twice daily if risk of Hypotension with Bradycardia, or conduction defect
- Titrate starting after 2 weeks
- Increase to 7.5 mg twice daily after 2 weeks if Heart Rate >60/min
- Decrease to 2.5 mg twice daily after 2 weeks if Heart Rate <50/min
VII. Adverse effects
-
Bradycardia (8-13%)
- Risk factors
- Combined with Beta Blockers, Amiodarone, Digoxin, Diltiazem
- Cardiac conduction disorders
- Low resting Heart Rate
- Monitor carefully while titrating dose
- Avoid in patients with resting Heart Rate <70/min
- Risk factors
- Atrial Fibrillation (1%)
- Third degree AV Block or Sick Sinus Syndrome
- Visual Field increased brightness (2%)
- Hypertension
VIII. Efficacy
- Prevents CHF hospitalizations (NNT 25)
- Does not reduce mortality
- Swedberg (2010) Lancet 376(9744): 875-85 [PubMed]
IX. Drug Interactions
- Strong CYP3A4 inhibitors potentiate Ivabradine
- Verapamil (also increases Bradycardia risk)
- Diltiazem (also increases Bradycardia risk)
- Macrolide Antibiotics
- Protease Inhibitors
- CYP3A4 Inducers reduce Ivabradine effect
XI. References
- (2015) Presc Lett 22(6): 31
- (2017) Presc Lett 24(7)
- Davis (2016) Am Fam Physician 93(8): 683-4 [PubMed]
- Swedberg (2010) Lancet 376(9744):875-85 +PMID:20801500 [PubMed]
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