Corlanor® is a first-in-class, HCN channel blocker
that lowers heart rate1,2

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HCN channel

Mixed sodium and potassium channel that carries the If current

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If current

Inward flow of positively charged ions that initiates the spontaneous diastolic depolarization phase, modulating heart rate

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Corlanor®

Within the SA node, selectively blocks the HCN channel, inhibits the If current, and lowers heart rate

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  • Corlanor® has no effect on myocardial contractility (no negative inotropic effect)
  • Corlanor® has no effect on ventricular repolarization
  • Reduction in heart rate with Corlanor® is both dose dependent and baseline heart rate dependent

Mechanism of action statements are not meant to imply clinical efficacy.

HCN = hyperpolarization-activated cyclic nucleotide-gated; SA = sinoatrial.

References
  1. Corlanor® (ivabradine) Prescribing Information, Amgen.
  2. DiFrancesco D. Funny channels in the control of cardiac rhythm and mode of action of selective blockers. Pharmacol Res. 2006;53:399-406.
IMPORTANT SAFETY INFORMATION
SEE MORELESS

IMPORTANT SAFETY INFORMATION Contraindications: Corlanor® is contraindicated in patients with acute decompensated heart failure, blood pressure < 90/50 mmHg, sick sinus syndrome, sinoatrial block, 3rd degree atrioventricular block (unless a functioning demand pacemaker is present), a resting heart rate < 60 bpm prior to treatment, severe hepatic impairment, pacemaker dependence (heart rate maintained exclusively by the pacemaker), and concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors.

Fetal Toxicity: Corlanor® may cause fetal toxicity when administered to a pregnant woman based on embryo-fetal toxicity and cardiac teratogenic effects observed in animal studies. Advise females to use effective contraception when taking Corlanor®.

Atrial Fibrillation: Corlanor® increases the risk of atrial fibrillation. The rate of atrial fibrillation in patients treated with Corlanor® compared to placebo was 5% vs. 3.9% per patient-year, respectively. Regularly monitor cardiac rhythm. Discontinue Corlanor® if atrial fibrillation develops.

Bradycardia and Conduction Disturbances: Bradycardia, sinus arrest and heart block have occurred with Corlanor®. The rate of bradycardia in patients treated with Corlanor® compared to placebo was 6% (2.7% symptomatic; 3.4% asymptomatic) vs. 1.3% per patient‐year, respectively. Risk factors for bradycardia include sinus node dysfunction, conduction defects, ventricular dyssynchrony, and use of other negative chronotropes. Bradycardia may increase the risk of QT prolongation which may lead to severe ventricular arrhythmias, including torsades de pointes, especially in patients with risk factors such as use of QTc prolonging drugs.

Concurrent use of verapamil or diltiazem also increases Corlanor® exposure, contributes to heart rate lowering, and should be avoided. Avoid use of Corlanor® in patients with 2nd degree atrioventricular block unless a functioning demand pacemaker is present

Adverse Reactions: The most common adverse drug reactions reported at least 1% more frequently with Corlanor® than placebo and that occurred in more than 1% of patients treated with Corlanor® were bradycardia (10% vs. 2.2%), hypertension or increased blood pressure (8.9% vs. 7.8%), atrial fibrillation (8.3% vs. 6.6%), and luminous phenomena (phosphenes) or visual brightness (2.8% vs. 0.5%).

In postmarketing experience, torsades de pointes has been observed.


INDICATION

Corlanor® (ivabradine) is indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction 35%, who are in sinus rhythm with resting heart rate 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.

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