Version October 2024
Heart failure with reduced ejection fraction (adjunctive agent):
Note: May be considered for additional therapy in patients who are persistently symptomatic despite an optimal medical regimen for heart failure with reduced ejection fraction. Consider for use in stable, euvolemic patients who are in sinus rhythm with resting heart rate ≥70 beats per minute (bpm) despite being on a target or maximally tolerated dose of beta blocker or if there is a contraindication to beta-blocker use (Ref).
Oral: Initial: 5 mg twice daily or 2.5 mg twice daily in patients with a history of conduction defects or who may experience hemodynamic compromise due to bradycardia. Adjust dose every ≥2 weeks as needed (Ref).
Dosage adjustment based on resting heart rate (Ref):
If heart rate >60 bpm: Increase dose by 2.5 mg twice daily; maximum dose: 7.5 mg twice daily.
If heart rate 50 to 60 bpm: Maintain dose.
If heart rate <50 bpm or signs and symptoms of bradycardia: Decrease dose by 2.5 mg twice daily; if current dose is 2.5 mg twice daily, discontinue therapy.
Stable angina (off-label use):
Note: Consider for use if symptoms are not controlled on beta-blocker or calcium channel blocker monotherapy. If combined with a calcium channel blocker, use of a dihydropyridine (such as slow-release nifedipine, amlodipine, or felodipine) is suggested (Ref).
Adults <75 years of age: Oral: Initial: 2.5 to 5 mg twice daily; titrate up in increments of 2.5 mg after 3 to 4 weeks if symptoms persist and heart rate is >60 bpm; maximum dose: 7.5 mg twice daily. Discontinue therapy if angina symptoms do not improve within 3 months of initiation. Also consider discontinuation if improvement of angina symptoms is limited and no clinically significant heart rate reduction occurs in the first 3 months. If heart rate is <50 bpm at rest or patient experiences symptomatic bradycardia (eg, dizziness, fatigue, hypotension) during therapy, decrease dose by 2.5 mg per dose, or discontinue if already at the minimum dose of 2.5 mg twice daily. Monitor heart rate carefully after dosage reduction. If heart rate continues to be <50 bpm or symptoms of bradycardia persist, discontinue therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥15 mL/minute: No dosage adjustment necessary.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): Use is contraindicated (has not been studied; increase in systemic exposure anticipated).
Heart failure with reduced ejection fraction: Adults ≥75 years of age: Initial: Oral: 2.5 mg twice daily. Refer to adult dosing for titration and maintenance dosing (Ref).
Stable angina (off-label use): Adults ≥75 years of age: Initial: Oral: Consider 2.5 mg twice daily. Titration and maintenance: Refer to adult dosing.
(For additional information see "Ivabradine: Pediatric drug information")
Heart failure, dilated cardiomyopathy:
Infants ≥6 months, Children, and Adolescents <18 years:
<40 kg: Oral: Initial: 0.05 mg/kg/dose twice daily; may increase dose every 2 weeks by 0.05 mg/kg/dose as tolerated to achieve a 20% reduction in heart rate without inducing bradycardia.
Maximum dose: Age-dependent:
≥6 months to <1 year: 0.2 mg/kg/dose twice daily.
≥1 year: 0.3 mg/kg/dose twice daily, not to exceed 7.5 mg/dose twice daily.
Dosage adjustment for bradycardia:
Initial dose: Decrease dose to 0.02 mg/kg/dose twice daily.
During titration: Decrease dose to previous dose.
≥40 kg: Oral: Initial: 2.5 mg twice daily; may increase dose every 2 weeks by 2.5 mg as tolerated to achieve a 20% reduction in heart rate without inducing bradycardia; maximum dose: 7.5 mg/dose twice daily.
Dosage adjustment for bradycardia: Decrease dose to previous dose.
Adolescents ≥18 years: Oral: Initial: 5 mg twice daily or 2.5 mg twice daily in patients with a history of conduction defects or who may experience hemodynamic compromise due to bradycardia; after 2 weeks, adjust dose to achieve a resting heart rate between 50 and 60 beats per minute (bpm); adjust dose as needed based on resting heart rate and tolerability; maximum dose: 7.5 mg/dose twice daily.
Dosage adjustment based on resting heart rate:
If heart rate >60 bpm: Increase dose by 2.5 mg twice daily; maximum dose: 7.5 mg/dose twice daily.
If heart rate 50 to 60 bpm: Maintain dose.
If heart rate <50 bpm or signs and symptoms of bradycardia: Decrease dose by 2.5 mg twice daily; if current dose is 2.5 mg twice daily, discontinue therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants ≥6 months, Children, and Adolescents:
CrCl ≥15 mL/minute: No dosage adjustment necessary.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Infants ≥6 months, Children, and Adolescents:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is contraindicated (has not been studied; increase in systemic exposure anticipated).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Bradycardia (4% to 10%), hypertension (9%), atrial fibrillation (8%)
Central nervous system: Phosphene (3%)
Frequency not defined: Cardiovascular: Heart block, sinoatrial arrest
<1%, postmarketing, and/or case reports: Angioedema, diplopia, erythema, hypotension, pruritus, skin rash, syncope, torsades de pointes, urticaria, ventricular fibrillation, ventricular tachycardia, vertigo, visual impairment
Acute decompensated heart failure; clinically significant hypotension; sick sinus syndrome, sinoatrial block, or third-degree AV block (unless a functioning demand pacemaker is present); clinically significant bradycardia; severe hepatic impairment; pacemaker dependence (heart rate maintained exclusively by the pacemaker); concomitant use with strong CYP3A4 inhibitors.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to ivabradine or any component of the formulation; resting heart rate <70 bpm prior to treatment; prolonged QT interval (eg, congenital long QT syndrome); cardiogenic shock; acute myocardial infarction; concomitant use of verapamil or diltiazem; pregnancy, breastfeeding, or women of child-bearing potential not using appropriate contraception; hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the congenital lactase deficiency.
Concerns related to adverse events:
• Atrial fibrillation: Use increases the risk of atrial fibrillation; monitor cardiac rhythm. Discontinue if atrial fibrillation develops.
• Bradycardia and conduction disturbances: Bradycardia, sinus arrest, and heart block may occur; monitor heart rate prior to initiation and with any dosage adjustment. Bradycardia may increase the risk of QT prolongation, which may lead to severe ventricular arrhythmias, including torsade de pointes, especially in patients with risk factors such as use of QTc prolonging drugs. 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). Avoid concurrent use with verapamil and diltiazem. Avoid use in patients with second-degree AV block (unless a functioning demand pacemaker is present). Use is contraindicated in patients with sick sinus syndrome, sinoatrial block, third-degree AV block (unless a functioning demand pacemaker is present), or pacemaker dependence. Decrease dose or discontinue use if heart rate <50 bpm persists during therapy or signs and symptoms of bradycardia occur. Use is contraindicated in patients with clinically significant bradycardia. In patients with history of conduction defects or in whom bradycardia could lead to hemodynamic compromise, initial dosage reduction is recommended. Heart rate reduction may prolong the uncorrected QT interval while QTc interval remains unchanged (Camm 2003; Murat 2009). At concentrations slightly higher than that achieved with therapeutic dosing, ivabradine prolonged ventricular repolarization in perfused guinea-pig hearts (Melgari 2015). Torsades de pointes has been reported when used with other drugs that produce bradycardia or prolong the QT interval (Cocco 2015; Mittal 2014).
• Visual function: Phosphenes (described as transient enhanced brightness in a limited area of the visual field, halos, image decomposition, colored bright lights, or multiple images) may occur with use. Onset is generally within the first 2 months of therapy and is reported to be of mild to moderate intensity; most cases resolve during or after treatment discontinuation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral [preservative free]:
Corlanor: 5 mg/5 mL (5 mL)
Tablet, Oral:
Corlanor: 5 mg [scored]
Corlanor: 7.5 mg
No
Solution (Corlanor Oral)
5 mg/5 mL (per mL): $2.38
Tablets (Corlanor Oral)
5 mg (per each): $11.92
7.5 mg (per each): $11.92
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lancora: 5 mg, 7.5 mg [contains corn starch]
Corlanor oral solution (for outpatient use) is exclusively distributed through Avella Specialty Pharmacy. Call 1-844-6CORLANOR or visit https://www.corlanorhcp.com/pediatric-indication for additional information.
Oral: Administer with food. Oral solution can be used for adults unable to swallow tablets. For oral solution, empty entire contents of ampule(s) into a medication cup; use a calibrated oral syringe to measure prescribed dose from the medication cup. Discard any unused oral solution.
Oral: Administer with food. For oral solution, empty entire contents of ampule(s) into a medication cup; use a calibrated oral syringe to measure prescribed dose from the medication cup. Discard any unused oral solution. Rinse oral syringe and medicine cup with warm, running water after use and air dry.
If a dose is missed or spit out, do not administer another dose; administer next dose at usual time.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Ivabradine may cause teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Corlanor: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206143s007lbl.pdf#page=24
Heart failure with reduced ejection fraction: To reduce the risk of hospitalization in adult patients with stable, symptomatic (NYHA class II to III) heart failure with left ventricular ejection fraction ≤35%, who are in sinus rhythm with resting heart rate ≥70 beats per minute despite being on a maximally tolerated dose of beta blocker or if there is a contraindication to beta-blocker use (ACC [Maddox 2021]).
Inappropriate sinus tachycardia; Stable angina
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Bradycardia-Causing Agents: May enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Ivabradine. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Ivabradine. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ivabradine. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ivabradine. Risk X: Avoid combination
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider therapy modification
Grapefruit Juice: May increase the serum concentration of Ivabradine. Risk X: Avoid combination
Itraconazole: May increase the serum concentration of Ivabradine. Risk X: Avoid combination
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Loop Diuretics: May enhance the arrhythmogenic effect of Ivabradine. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May enhance the arrhythmogenic effect of Ivabradine. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Food: Absorption delayed by 1 hour and AUC increased by 20% to 40% when taken with food. Management: Take with food to reduce variability in exposure.
Grapefruit juice: Exposure increased twofold after ingestion of grapefruit juice. Management: Avoid consumption of grapefruit juice (Nawarskas 2015).
Effective contraception is recommended in patients who could become pregnant.
Patients with heart failure who are planning a pregnancy should be transitioned to an agent preferred for use in pregnant patients prior to conception (AHA/ACC/HFSA [Heidenreich 2022]).
Outcome data following maternal use of ivabradine during pregnancy are limited (Babic 2011; Haghikia 2016; Hoeltzenbein 2021; Sağ 2016; Tonko 2021).
Ivabradine is not recommended for the treatment of heart failure in pregnant patients (AHA/ACC/HFSA [Heidenreich 2022]). If treatment is needed during pregnancy, close maternal and fetal monitoring is recommended (Hoeltzenbein 2021).
It is not known if ivabradine is present in breast milk.
Outcome data following maternal use of ivabradine while breastfeeding are limited (Sağ 2016). Due to the potential risk from exposure in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Heart rate (prior to initiation, prior to increasing dose, or after decreasing dose); monitor heart rate more closely if receiving other negative chronotropes (eg, amiodarone, beta-blockers, digoxin); blood pressure; regularly monitor cardiac rhythm (assessing for atrial fibrillation)
Selective and specific inhibition of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (f-channels) within the sinoatrial (SA) node of cardiac tissue resulting in disruption of I f ion current flow prolonging diastolic depolarization, slowing firing in the SA node, and ultimately reducing heart rate. Has not demonstrated effects on myocardial contractility or relaxation, ventricular repolarization, or conduction apart from the sinus node effects. Partial inhibition of the retinal I h current (similar to the cardiac I f current) may explain visual disturbances (eg, phosphenes) (Nawarskas 2015).
Note: Pharmacokinetic data (drug exposure) in pediatric patients 6 months to <18 years of age were observed to be similar to adults.
Distribution: Vd: ~100 L
Protein binding: ~70%
Metabolism: Extensively intestinal and hepatic via CYP3A4; major active metabolite equipotent to ivabradine is the N-desmethylated derivative (S 18982) which is also metabolized by CYP3A4
Bioavailability: ~40%; AUC increased 20% to 40% with food
Half-life elimination: Distribution: 2 hours; Effective: ~6 hours
Time to peak, plasma: ~1 hour (fasting); ~2 hours (with food)
Excretion: Feces and urine (~4% as unchanged drug)
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