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Accession Number
Small Molecule

Ivabradine is a novel heart rate lowering medicine for the symptomatic management of stable angina pectoralis and symptomatic chronic heart failure. Ivabradine, brand name Corlanor, was approved by the FDA in April 2015 for the treatment of chronic heart failure in patients with an ejection fraction of ≤35%, in sinus rhythm with resting heart rate ≥70 beats per minute, who are not on beta-blockers due to contraindications or already receiving maximum beta-blocker dose. Recently a new indication was added to treat symptomatic heart failure from dilated cardiomyopathy for patients 6 months or more in ageLabel. Ivabradine acts by selectively inhibiting the "funny" channel pacemaker current (If) in the sinoatrial node in a dose-dependent fashion, resulting in a lower heart rate and thus more blood to flow to the myocardium. Although non-dihydropyridine calcium channel blockers and beta blockers also effectively lower heart rate, they exhibit adverse events due to their negative ionotropic effects. Therefore, as ivabradine is designed as a "pure" heart rate-lowering drug by selectively acting on the If channels, it may offer a more favorable side effect profile due to its lower likelihood of causing serious adverse effects.

  • 3-[3-({[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino)propyl]-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one
  • Ivabradin
  • Ivabradina
  • Ivabradine
  • Ivabradinum
External IDs
S 16257
Product Ingredients
IngredientUNIICASInChI Key
Ivabradine hydrochlorideTP19837BZK148849-67-6HLUKNZUABFFNQS-ZMBIFBSDSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CorlanorSolution5 mg/5mLOralAMGEN INC2019-04-19Not applicableUs
CorlanorTablet, film coated7.5 mg/1OralAMGEN INC2015-04-20Not applicableUs
CorlanorTablet, film coated5 mg/1OralAMGEN INC2015-04-20Not applicableUs
CorlentorTablet, film coated7.5 mgOralLes Laboratoires Servier2005-10-25Not applicableEu
CorlentorTablet, film coated7.5 mgOralLes Laboratoires Servier2005-10-25Not applicableEu
CorlentorTablet, film coated5 mgOralLes Laboratoires Servier2005-10-25Not applicableEu
CorlentorTablet, film coated7.5 mgOralLes Laboratoires Servier2005-10-25Not applicableEu
CorlentorTablet, film coated5 mgOralLes Laboratoires Servier2005-10-25Not applicableEu
CorlentorTablet, film coated5 mgOralLes Laboratoires Servier2005-10-25Not applicableEu
CorlentorTablet, film coated7.5 mgOralLes Laboratoires Servier2005-10-25Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Bradia (Biocon) / Ivabid
CAS number
Average: 468.594
Monoisotopic: 468.262422267
Chemical Formula
InChI Key



Ivabradine is indicated by the FDA to reduce the risk of hospitalization for worsening heart failure in adult 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. It is also indicated for treatment of stable symptomatic heart failure as a result of dilated cardiomyopathy for pediatric patients 6 months of age or moreLabel.

Associated Conditions

The funny channels (If) open during repolarization and close during depolarization, making ivabradine's activity dependent on heart rate or the closing and opening of the channels. Therefore ivabradine exhibits use-dependence and is more pharmacologically active at higher heart rates. Ivabradine exhibits a linear dose-dependent heart-rate lowering activity (bradycardic effect) until a maximum dose of 30-40mg. At higher doses, the concentration of ivabradine tends to plateau, reducing risk of serious sinus bradycardia. It has been shown that the metabolite of ivabradine lowers heart rate as well, contributing to ivabradine's overall effect.

Mechanism of action

Ivabradine lowers heart rate by selectively inhibiting If channels ("funny channels") in the heart in a concentration-dependent manner without affecting any other cardiac ionic channels (including calcium or potassium). Ivabradine binds by entering and attaching to a site on the channel pore from the intracellular side and disrupts If ion current flow, which prolongs diastolic depolarization, lowering heart rate. The If currents are located in the sinoatrial node and are the home of all cardiac pacemaker activity. Ivabradine therefore lowers the pacemaker firing rate, consequently lowering heart rate and reducing myocardial oxygen demand. This allows for an improved oxygen supply and therefore mitigation of ischemia, allowing for a higher exercise capacity and reduction in angina episodes.

UPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
Additional Data Available
Adverse Effects

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Blackbox Warnings

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It is recommended to take ivabradine with food to reduce variability in systemic exposure. Administration with food slows absorption by 1 hour, but increases systemic absorption by 20-30%. Ivabradine's oral bioavailability is about 40%.

Volume of distribution

~100 L.

Protein binding

70% bound to plasma proteins.


Ivabradine is extensively metabolized by oxidation in the gut and liver by cytochrome P450 3A4 enzyme. Its active metabolite, N-desmethylated derivative, is also metabolized by CYP 3A4. Ivabradine's affinity for CYP 3A4 is low, making it unlikely to affect the metabolism of other drugs; however potent inhibitors or inducers of CYP 3A4 may affect ivabradine's plasma concentration and pharmacodynamic effects and should not be co-administered.

Route of elimination

Metabolites are equally excreted in feces and urine.

Half life

2 hours.


Total clearance is about 400ml/min; renal clearance about 70ml/min. About 4% is excreted unchanged in urine.


Ivabradine may cause fetal toxicity when administered to pregnant women. Animal studies in pregnant rats have shown embryo-fetal toxicity and cardiac teratogenic effects. Effective contraception in women is recommended while using ivabradine.

Affected organisms
  • Humans and other mammals
Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
AbexinostatIvabradine may increase the QTc-prolonging activities of Abexinostat.
AcebutololAcebutolol may increase the bradycardic activities of Ivabradine.
AceprometazineIvabradine may increase the QTc-prolonging activities of Aceprometazine.
AcetyldigoxinIvabradine may increase the bradycardic activities of Acetyldigoxin.
AcrivastineThe risk or severity of QTc prolongation can be increased when Acrivastine is combined with Ivabradine.
AdenosineIvabradine may increase the QTc-prolonging activities of Adenosine.
AgmatineAgmatine may increase the bradycardic activities of Ivabradine.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Ivabradine.
AlfentanilAlfentanil may increase the bradycardic activities of Ivabradine.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Ivabradine.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity

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  • Evidence Level
    Evidence Level

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  • Action

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Food Interactions
  • Grapefruit juice may increase ivabradine exposure by twofold (due to its inhibition of CYP3A4). Therefore grapefruit juice consumption is not recommended while taking ivabradine.


General References
  1. DiFrancesco D: The role of the funny current in pacemaker activity. Circ Res. 2010 Feb 19;106(3):434-46. doi: 10.1161/CIRCRESAHA.109.208041. [PubMed:20167941]
  2. Sulfi S, Timmis AD: Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina. Int J Clin Pract. 2006 Feb;60(2):222-8. [PubMed:16451297]
  3. DiFrancesco D, Camm JA: Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs. 2004;64(16):1757-65. [PubMed:15301560]
  4. Nawarskas JJ, Bowman BN, Anderson JR: Ivabradine: A Unique and Intriguing Medication for Treating Cardiovascular Disease. Cardiol Rev. 2015 Jul-Aug;23(4):201-11. doi: 10.1097/CRD.0000000000000070. [PubMed:25839989]
  5. Rosa GM, Ferrero S, Ghione P, Valbusa A, Brunelli C: An evaluation of the pharmacokinetics and pharmacodynamics of ivabradine for the treatment of heart failure. Expert Opin Drug Metab Toxicol. 2014 Feb;10(2):279-91. doi: 10.1517/17425255.2014.876005. Epub 2013 Dec 31. [PubMed:24377458]
  6. hERG potassium channel inhibition by ivabradine may contribute to QT prolongation and risk of torsades de pointes [Link]
External Links
PubChem Compound
PubChem Substance
RxList Drug Page Drug Page
ATC Codes
C01EB17 — IvabradineC07FX05 — Metoprolol and ivabradineC07FX06 — Carvedilol and ivabradine
AHFS Codes
  • 24:04.92 — Miscellaneous Cardiac Drugs
FDA label
Download (1.43 MB)
Download (23.8 KB)

Clinical Trials

Clinical Trials
1CompletedTreatmentHealthy Individuals1
1RecruitingTreatmentAtrial Fibrillation (AF) / Atrial Fibrillation, Persistent1
1, 2RecruitingTreatmentDecompensated Heart Failure1
2CompletedNot AvailableCongestive Heart Failure1
2RecruitingTreatmentAngina Pectoris1
2RecruitingTreatmentAutonomic Nervous System Imbalance / Cancer Survivorship / Malignant Lymphomas1
2Unknown StatusBasic SciencePostural Orthostatic Tachycardia Syndrome (POTS)1
2Unknown StatusTreatmentMultiple Organ Dysfunction Syndrome1
2Unknown StatusTreatmentPostural Tachycardia Syndrome1
2WithdrawnTreatmentDiastolic Heart Failure1
3CompletedNot AvailableAngina Pectoris1
3CompletedTreatmentChronic Heart Failure (CHF)1
3CompletedTreatmentCoronary Artery Disease1
3CompletedTreatmentCoronary Heart Disease (CHD) / Ventricular Dysfunction, Left1
3CompletedTreatmentHeart Failure1
3CompletedTreatmentInappropriate Sinus Tachycardia1
3CompletedTreatmentMitral Valve Stenosis1
3Not Yet RecruitingTreatmentShock, Septic1
3RecruitingTreatmentAging / Healthy Volunteers / Vascular Stiffness1
3RecruitingTreatmentAtrial Fibrillation (AF) / Heart Diseases1
3RecruitingTreatmentDiabetic Kidney Disease1
3RecruitingTreatmentPatients With Cancer1
3RecruitingTreatmentPostural Orthostatic Tachycardia Syndrome (POTS)1
3WithdrawnSupportive CareHeart Transplantation, Elevated Resting Heart Rate1
4CompletedTreatmentAsthma-chronic obstructive pulmonary disease overlap syndrome1
4CompletedTreatmentCardiac Failure1
4CompletedTreatmentChronic Stable Angina Pectoris1
4CompletedTreatmentCoronary Artery Disease1
4CompletedTreatmentHeart Failure3
4Not Yet RecruitingTreatmentShock, Cardiogenic1
4Not Yet RecruitingTreatmentChronic heart failure with reduced ejection fraction (NYHA Class IV)1
4RecruitingBasic ScienceDilated Cardiomyopathies, Idiopathic / Electrical Remodeling / Heart Failure, Systolic / Ventricular Remodelling1
4RecruitingTreatmentCardiac Allograft Vasculopathy / Transplanted Heart Complication1
4RecruitingTreatmentHeart Failure1
4RecruitingTreatmentHeart Failure / Shock, Cardiogenic / Tachycardia1
4SuspendedTreatmentHeart Rate Control in ICD Patients With Heart Failure1
4Unknown StatusDiagnosticCoronary Arteriosclerosis / Coronary Artery Disease1
4Unknown StatusDiagnosticCoronary Artery Disease1
4Unknown StatusTreatmentAcute Coronary Syndromes (ACS)1
4Unknown StatusTreatmentAnginal Pain / Coronary Heart Disease (CHD) / Hemodialysis Treatment1
4Unknown StatusTreatmentHeart Failure2
4Unknown StatusTreatmentHigh Heart Rate1
4WithdrawnBasic ScienceBlood Pressures1
4WithdrawnBasic ScienceCentral Arterial Pressure1
4WithdrawnTreatmentAnginal Pain / Coronary Artery Disease1
Not AvailableActive Not RecruitingTreatmentDecompensated Heart Failure / Heart Failure With Reduced Ejection Fraction (HFrEF)1
Not AvailableCompletedNot AvailableAtrial Fibrillation (AF) / Cardiac Failure With Sinus Rhythm or Atrial Fibrillation / Heart Failure1
Not AvailableCompletedNot AvailableBradycardia1
Not AvailableCompletedNot AvailableChronic Heart Failure (CHF)1
Not AvailableCompletedNot AvailableHeart Failure1
Not AvailableCompletedTreatmentChronic Liver Diseases (CLD) / Diastolic Dysfunction1
Not AvailableCompletedTreatmentCoronary Artery Disease1
Not AvailableNot Yet RecruitingTreatmentCirrhotic Cardiomyopathy / Liver Cirrhosis / Portal Hypertension / Symptomatic left ventricular ejection fraction ≤ 35% Chronic heart failure1
Not AvailableNot Yet RecruitingTreatmentSevere Sepsis1
Not AvailableRecruitingPreventionCardiotoxicity / Chemotherapy Effect / Heart Failure / Neoplasms / Oncology1
Not AvailableRecruitingSupportive CareCongestive Heart Failure / CT Angiography / Heart Failure / Heart Failure, Diastolic / Heart Failure, Systolic / Heart Rate Low / Ischaemic Cardiomyopathy / Non-ischaemic Cardiomyopathy1
Not AvailableRecruitingTreatmentChronic Heart Failure (CHF)1
Not AvailableUnknown StatusTreatmentAtrial Fibrillation (AF) / Chronic Heart Failure (CHF) / Sinus Arrhythmia1


Not Available
Not Available
Dosage forms
SolutionOral5 mg/5mL
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral7.5 mg/1
Tablet, film coatedOral5 mg
Tablet, film coatedOral7.5 mg
Not Available
Patent NumberPediatric ExtensionApprovedExpires (estimated)
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Experimental Properties
Not Available
Predicted Properties
Water Solubility0.0202 mg/mLALOGPS
pKa (Strongest Basic)9.37ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area60.47 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity133.51 m3·mol-1ChemAxon
Polarizability54.56 Å3ChemAxon
Number of Rings4ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available


This compound belongs to the class of organic compounds known as benzazepines. These are organic compounds containing a benzene ring fused to an azepine ring (unsaturated seven-membered heterocycle with one nitrogen atom replacing a carbon atom).
Organic compounds
Super Class
Organoheterocyclic compounds
Sub Class
Not Available
Direct Parent
Alternative Parents
Anisoles / Azepines / Aralkylamines / Alkyl aryl ethers / Tertiary carboxylic acid amides / Trialkylamines / Lactams / Amino acids and derivatives / Azacyclic compounds / Organopnictogen compounds
show 3 more
Benzazepine / Anisole / Alkyl aryl ether / Azepine / Aralkylamine / Benzenoid / Tertiary carboxylic acid amide / Carboxamide group / Amino acid or derivatives / Tertiary aliphatic amine
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, aromatic ether, benzazepine, carbobicyclic compound (CHEBI:85966)


Pharmacological action
General Function
Voltage-gated sodium channel activity
Specific Function
Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transpor...
Gene Name
Uniprot ID
Uniprot Name
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
Molecular Weight
96949.43 Da
  1. hERG potassium channel inhibition by ivabradine may contribute to QT prolongation and risk of torsades de pointes [Link]


Pharmacological action
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
Uniprot ID
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
  1. Rosa GM, Ferrero S, Ghione P, Valbusa A, Brunelli C: An evaluation of the pharmacokinetics and pharmacodynamics of ivabradine for the treatment of heart failure. Expert Opin Drug Metab Toxicol. 2014 Feb;10(2):279-91. doi: 10.1517/17425255.2014.876005. Epub 2013 Dec 31. [PubMed:24377458]

Drug created on September 14, 2015 09:24 / Updated on November 20, 2019 12:30