ivabradine

Adult Dosing

Heart failure

Initial dose: 5mg PO BID with meals
After 2 weeks, assess the patient and adjust the dose to achieve a resting heart rate of 50-60 bpm. Thereafter, adjust the dose, if necessary, based on resting heart rate and tolerability, as given below

Dose adjustment

If HR >60 bpm: Increase the dose by 2.5 mg (BID) up to a maximum dose of 7.5 mg BID
If HR is 50-60 bpm: Maintain the dose
If HR <50 bpm or signs and symptoms of bradycardia: Decrease the dose by 2.5 mg (BID); if current dose is 2.5 mg BID, discontinue therapy

Pediatric Dosing

[Outline]

Indications ⬆ ⬇

To reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with LVEF 35% who are in sinus rhythm with resting heart rate 70 bpm and are either on maximally tolerated doses of beta-blockers or in whom beta-blockers are contraindicated

Contraindications ⬆ ⬇

Hypersensitivity to any of the ingredients of the product
Acute decompensated heart failure
Blood pressure less than 90/50 mmHg
Sick sinus syndrome, sinoatrial block, or 3rd degree AV block, unless a functioning demand pacemaker is present
Resting heart rate less than 60 bpm prior to treatment
Severe hepatic impairment
Pacemaker dependence (heart rate maintained exclusively by the pacemaker)
Concomitant use of strong CYP3A4 inhibitors

Black Box Warnings ⬆ ⬇

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Hepatic Dose Adjustment

Warnings/Precautions ⬆ ⬇

Animal studies have reported embryo-fetal toxicity and cardiac teratogenic effects of ivabradine. Advise women to use effective contraception when taking ivabradine
Ivabradine increases risk of atrial fibrillation. Monitor cardiac rhythm regularly. Discontinue ivabradine if atrial fibrillation develops
Bradycardia, sinus arrest, and heart block have been reported with ivabradine. Risk factors for bradycardia include sinus node dysfunction, conduction defects (eg, first or second degree AV block, bundle-branch block), ventricular dyssynchrony, and use of other negative chronotropes (eg, digoxin, diltiazem, verapamil, amiodarone). Also, concurrent use of verapamil or diltiazem increases ivabradine systemic exposure and should be avoided. Avoid use in patients with second-degree AV block unless a functioning demand pacemaker is present

Interactions ⬆ ⬇

Corlanor interacts with :

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category: Not rated

Pregnant patients started on ivabradine, especially during the first trimester, should be followed closely for destabilization of their congestive heart failure which can result from heart rate slowing
Pregnant women with chronic heart failure should be monitored for preterm birth in 3rd trimester of pregnancy

Breastfeeding: Breastfeeding is not recommended because of the potential risk to breastfed infants from exposure to ivabradine.

Adverse Reactions ⬆ ⬇

Clinical Pharmacology ⬆ ⬇

Selective I(f) Current Inhibitor; blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) current, which regulates heart rate
Absolute Bioavailability: 40%
Metabolism: Extensively metabolized in the liver and intestines by CYP3A4-mediated oxidation; major metabolite is N-desmethylated derivative (S 18982)
Excretion: Excreted in urine (4%) and feces
Half-life: Distribution half-life: 2 hrs Effective half-life: approx 6 hrs

Brands and Availability ⬆ ⬇