Identification

Name
Ivabradine
Accession Number
DB09083
Type
Small Molecule
Groups
Approved
Description

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. 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.

Structure
Thumb
Synonyms
  • 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
CorlanorTablet, film coated5 mg/1OralAmgen2015-04-20Not applicableUs
CorlanorTablet, film coated7.5 mg/1OralAmgen2015-04-20Not applicableUs
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
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 coated7.5 mgOralLes Laboratoires Servier2005-10-25Not applicableEu
International/Other Brands
Bradia (Biocon) / Ivabid
Categories
UNII
3H48L0LPZQ
CAS number
155974-00-8
Weight
Average: 468.594
Monoisotopic: 468.262422267
Chemical Formula
C27H36N2O5
InChI Key
ACRHBAYQBXXRTO-OAQYLSRUSA-N
InChI
InChI=1S/C27H36N2O5/c1-28(17-21-11-20-14-25(33-4)26(34-5)16-22(20)21)8-6-9-29-10-7-18-12-23(31-2)24(32-3)13-19(18)15-27(29)30/h12-14,16,21H,6-11,15,17H2,1-5H3/t21-/m1/s1
IUPAC Name
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
SMILES
COC1=C(OC)C=C2[[email protected]@H](CN(C)CCCN3CCC4=CC(OC)=C(OC)C=C4CC3=O)CC2=C1

Pharmacology

Indication

Ivabradine's indication by the FDA is 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.

Structured Indications
Pharmacodynamics

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.

Absorption

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.

Metabolism

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.

Clearance

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

Toxicity

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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcebutololAcebutolol may increase the bradycardic activities of Ivabradine.Approved
AmiodaroneAmiodarone may increase the bradycardic activities of Ivabradine.Approved, Investigational
AnagrelideIvabradine may increase the QTc-prolonging activities of Anagrelide.Approved
Arsenic trioxideIvabradine may increase the QTc-prolonging activities of Arsenic trioxide.Approved, Investigational
ArtemetherIvabradine may increase the QTc-prolonging activities of Artemether.Approved
AsenapineIvabradine may increase the QTc-prolonging activities of Asenapine.Approved
AtazanavirThe serum concentration of Ivabradine can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololAtenolol may increase the bradycardic activities of Ivabradine.Approved
AtomoxetineThe serum concentration of Ivabradine can be increased when it is combined with Atomoxetine.Approved
AzithromycinIvabradine may increase the QTc-prolonging activities of Azithromycin.Approved
BedaquilineIvabradine may increase the QTc-prolonging activities of Bedaquiline.Approved
BendroflumethiazideBendroflumethiazide may increase the arrhythmogenic activities of Ivabradine.Approved
BeractantBeractant may increase the bradycardic activities of Ivabradine.Approved
BetaxololBetaxolol may increase the bradycardic activities of Ivabradine.Approved
BisoprololBisoprolol may increase the bradycardic activities of Ivabradine.Approved
BoceprevirThe serum concentration of Ivabradine can be increased when it is combined with Boceprevir.Withdrawn
BortezomibThe serum concentration of Ivabradine can be increased when it is combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Ivabradine can be decreased when it is combined with Bosentan.Approved, Investigational
BretyliumBretylium may increase the bradycardic activities of Ivabradine.Approved
BumetanideBumetanide may increase the arrhythmogenic activities of Ivabradine.Approved
CalfactantCalfactant may increase the bradycardic activities of Ivabradine.Approved
CarbamazepineThe serum concentration of Ivabradine can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarteololCarteolol may increase the bradycardic activities of Ivabradine.Approved
CarvedilolCarvedilol may increase the bradycardic activities of Ivabradine.Approved, Investigational
ChloroquineIvabradine may increase the QTc-prolonging activities of Chloroquine.Approved, Vet Approved
ChlorothiazideChlorothiazide may increase the arrhythmogenic activities of Ivabradine.Approved, Vet Approved
ChlorpromazineIvabradine may increase the QTc-prolonging activities of Chlorpromazine.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the arrhythmogenic activities of Ivabradine.Approved
CiprofloxacinIvabradine may increase the QTc-prolonging activities of Ciprofloxacin.Approved, Investigational
CisaprideIvabradine may increase the QTc-prolonging activities of Cisapride.Approved, Investigational, Withdrawn
CitalopramIvabradine may increase the QTc-prolonging activities of Citalopram.Approved
ClarithromycinThe serum concentration of Ivabradine can be increased when it is combined with Clarithromycin.Approved
ClemastineThe serum concentration of Ivabradine can be increased when it is combined with Clemastine.Approved
ClonidineClonidine may increase the bradycardic activities of Ivabradine.Approved
ClotrimazoleThe serum concentration of Ivabradine can be increased when it is combined with Clotrimazole.Approved, Vet Approved
ClozapineIvabradine may increase the QTc-prolonging activities of Clozapine.Approved
CobicistatThe serum concentration of Ivabradine can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Ivabradine can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibCrizotinib may increase the bradycardic activities of Ivabradine.Approved
CyclopenthiazideCyclopenthiazide may increase the arrhythmogenic activities of Ivabradine.Experimental
CyclosporineThe serum concentration of Ivabradine can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Ivabradine can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Ivabradine can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Ivabradine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Ivabradine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe serum concentration of Ivabradine can be increased when it is combined with Delavirdine.Approved
DexmedetomidineDexmedetomidine may increase the bradycardic activities of Ivabradine.Approved, Vet Approved
DigoxinDigoxin may increase the bradycardic activities of Ivabradine.Approved
DihydroergotamineThe serum concentration of Ivabradine can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemDiltiazem may increase the bradycardic activities of Ivabradine.Approved
DisopyramideIvabradine may increase the QTc-prolonging activities of Disopyramide.Approved
DofetilideIvabradine may increase the QTc-prolonging activities of Dofetilide.Approved
DolasetronIvabradine may increase the QTc-prolonging activities of Dolasetron.Approved
DomperidoneIvabradine may increase the QTc-prolonging activities of Domperidone.Approved, Investigational, Vet Approved
DonepezilDonepezil may increase the bradycardic activities of Ivabradine.Approved
DoxycyclineThe serum concentration of Ivabradine can be increased when it is combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneDronedarone may increase the bradycardic activities of Ivabradine.Approved
DroperidolIvabradine may increase the QTc-prolonging activities of Droperidol.Approved, Vet Approved
EliglustatIvabradine may increase the QTc-prolonging activities of Eliglustat.Approved
ErythromycinThe serum concentration of Ivabradine can be increased when it is combined with Erythromycin.Approved, Vet Approved
EscitalopramIvabradine may increase the QTc-prolonging activities of Escitalopram.Approved, Investigational
EsmololEsmolol may increase the bradycardic activities of Ivabradine.Approved
Etacrynic acidEtacrynic acid may increase the arrhythmogenic activities of Ivabradine.Approved
FingolimodFingolimod may increase the bradycardic activities of Ivabradine.Approved, Investigational
FlecainideIvabradine may increase the QTc-prolonging activities of Flecainide.Approved, Withdrawn
FluconazoleThe serum concentration of Ivabradine can be increased when it is combined with Fluconazole.Approved
FluoxetineIvabradine may increase the QTc-prolonging activities of Fluoxetine.Approved, Vet Approved
FlupentixolIvabradine may increase the QTc-prolonging activities of Flupentixol.Approved, Withdrawn
FluvoxamineThe serum concentration of Ivabradine can be increased when it is combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe serum concentration of Ivabradine can be increased when it is combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Ivabradine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Ivabradine can be decreased when it is combined with Fosphenytoin.Approved
FurosemideFurosemide may increase the arrhythmogenic activities of Ivabradine.Approved, Vet Approved
Fusidic AcidThe serum concentration of Ivabradine can be increased when it is combined with Fusidic Acid.Approved
Gadobenic acidIvabradine may increase the QTc-prolonging activities of Gadobenic acid.Approved
GalantamineGalantamine may increase the bradycardic activities of Ivabradine.Approved
GemifloxacinIvabradine may increase the QTc-prolonging activities of Gemifloxacin.Approved, Investigational
GoserelinIvabradine may increase the QTc-prolonging activities of Goserelin.Approved
GranisetronIvabradine may increase the QTc-prolonging activities of Granisetron.Approved, Investigational
GuanfacineGuanfacine may increase the bradycardic activities of Ivabradine.Approved, Investigational
HaloperidolIvabradine may increase the QTc-prolonging activities of Haloperidol.Approved
HydrochlorothiazideHydrochlorothiazide may increase the arrhythmogenic activities of Ivabradine.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the arrhythmogenic activities of Ivabradine.Approved
IbutilideIvabradine may increase the QTc-prolonging activities of Ibutilide.Approved
IdelalisibThe serum concentration of Ivabradine can be increased when it is combined with Idelalisib.Approved
IloperidoneIvabradine may increase the QTc-prolonging activities of Iloperidone.Approved
ImatinibThe serum concentration of Ivabradine can be increased when it is combined with Imatinib.Approved
IndapamideIndapamide may increase the arrhythmogenic activities of Ivabradine.Approved
IndinavirThe serum concentration of Ivabradine can be increased when it is combined with Indinavir.Approved
IsavuconazoniumThe serum concentration of Ivabradine can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsradipineThe serum concentration of Ivabradine can be increased when it is combined with Isradipine.Approved
ItraconazoleThe serum concentration of Ivabradine can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Ivabradine can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Ivabradine can be increased when it is combined with Ketoconazole.Approved, Investigational
LabetalolLabetalol may increase the bradycardic activities of Ivabradine.Approved
LacosamideIvabradine may increase the atrioventricular blocking (AV block) activities of Lacosamide.Approved
LanreotideLanreotide may increase the bradycardic activities of Ivabradine.Approved
LenvatinibIvabradine may increase the QTc-prolonging activities of Lenvatinib.Approved
LeuprolideIvabradine may increase the QTc-prolonging activities of Leuprolide.Approved, Investigational
LevobunololLevobunolol may increase the bradycardic activities of Ivabradine.Approved
LevofloxacinIvabradine may increase the QTc-prolonging activities of Levofloxacin.Approved, Investigational
LopinavirThe serum concentration of Ivabradine can be increased when it is combined with Lopinavir.Approved
LovastatinThe serum concentration of Ivabradine can be increased when it is combined with Lovastatin.Approved, Investigational
LucinactantLucinactant may increase the bradycardic activities of Ivabradine.Approved
LumacaftorThe serum concentration of Ivabradine can be decreased when it is combined with Lumacaftor.Approved
LumefantrineIvabradine may increase the QTc-prolonging activities of Lumefantrine.Approved
MethadoneIvabradine may increase the QTc-prolonging activities of Methadone.Approved
MethyclothiazideMethyclothiazide may increase the arrhythmogenic activities of Ivabradine.Approved
MethyldopaMethyldopa may increase the bradycardic activities of Ivabradine.Approved
MetipranololMetipranolol may increase the bradycardic activities of Ivabradine.Approved
MetolazoneMetolazone may increase the arrhythmogenic activities of Ivabradine.Approved
MetoprololMetoprolol may increase the bradycardic activities of Ivabradine.Approved, Investigational
MoxifloxacinIvabradine may increase the QTc-prolonging activities of Moxifloxacin.Approved, Investigational
NadololNadolol may increase the bradycardic activities of Ivabradine.Approved
NebivololNebivolol may increase the bradycardic activities of Ivabradine.Approved, Investigational
NefazodoneThe serum concentration of Ivabradine can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Ivabradine can be increased when it is combined with Nelfinavir.Approved
NevirapineThe serum concentration of Ivabradine can be increased when it is combined with Nevirapine.Approved
NilotinibThe serum concentration of Ivabradine can be increased when it is combined with Nilotinib.Approved, Investigational
OctreotideOctreotide may increase the bradycardic activities of Ivabradine.Approved, Investigational
OfloxacinIvabradine may increase the QTc-prolonging activities of Ofloxacin.Approved
OlaparibThe serum concentration of Ivabradine can be increased when it is combined with Olaparib.Approved
OndansetronIvabradine may increase the QTc-prolonging activities of Ondansetron.Approved
OsimertinibThe serum concentration of Ivabradine can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Ivabradine can be increased when it is combined with Palbociclib.Approved
PaliperidoneIvabradine may increase the QTc-prolonging activities of Paliperidone.Approved
PanobinostatIvabradine may increase the QTc-prolonging activities of Panobinostat.Approved, Investigational
PasireotidePasireotide may increase the bradycardic activities of Ivabradine.Approved
PazopanibIvabradine may increase the QTc-prolonging activities of Pazopanib.Approved
PenbutololPenbutolol may increase the bradycardic activities of Ivabradine.Approved, Investigational
PentamidineIvabradine may increase the QTc-prolonging activities of Pentamidine.Approved
PentobarbitalThe serum concentration of Ivabradine can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PerflutrenIvabradine may increase the QTc-prolonging activities of Perflutren.Approved
PhenobarbitalThe serum concentration of Ivabradine can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Ivabradine can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimozideIvabradine may increase the QTc-prolonging activities of Pimozide.Approved
PindololPindolol may increase the bradycardic activities of Ivabradine.Approved
PiretanidePiretanide may increase the arrhythmogenic activities of Ivabradine.Experimental
PolythiazidePolythiazide may increase the arrhythmogenic activities of Ivabradine.Approved
Poractant alfaPoractant alfa may increase the bradycardic activities of Ivabradine.Approved
PosaconazoleThe serum concentration of Ivabradine can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimaquineIvabradine may increase the QTc-prolonging activities of Primaquine.Approved
PrimidoneThe serum concentration of Ivabradine can be decreased when it is combined with Primidone.Approved, Vet Approved
ProcainamideIvabradine may increase the QTc-prolonging activities of Procainamide.Approved
PromazineIvabradine may increase the QTc-prolonging activities of Promazine.Approved, Vet Approved
PropafenonePropafenone may increase the bradycardic activities of Ivabradine.Approved
PropranololPropranolol may increase the bradycardic activities of Ivabradine.Approved, Investigational
QuetiapineIvabradine may increase the QTc-prolonging activities of Quetiapine.Approved
QuinethazoneQuinethazone may increase the arrhythmogenic activities of Ivabradine.Approved
QuinidineIvabradine may increase the QTc-prolonging activities of Quinidine.Approved
QuinineIvabradine may increase the QTc-prolonging activities of Quinine.Approved
RanolazineThe serum concentration of Ivabradine can be increased when it is combined with Ranolazine.Approved, Investigational
RegorafenibRegorafenib may increase the bradycardic activities of Ivabradine.Approved
RifabutinThe serum concentration of Ivabradine can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Ivabradine can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Ivabradine can be decreased when it is combined with Rifapentine.Approved
RitonavirThe serum concentration of Ivabradine can be increased when it is combined with Ritonavir.Approved, Investigational
RivastigmineRivastigmine may increase the bradycardic activities of Ivabradine.Approved, Investigational
RuxolitinibRuxolitinib may increase the bradycardic activities of Ivabradine.Approved
SaquinavirThe serum concentration of Ivabradine can be increased when it is combined with Saquinavir.Approved, Investigational
SildenafilThe serum concentration of Ivabradine can be increased when it is combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Ivabradine can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Ivabradine can be increased when it is combined with Simeprevir.Approved
SotalolSotalol may increase the bradycardic activities of Ivabradine.Approved
St. John's WortThe serum concentration of Ivabradine can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Ivabradine can be increased when it is combined with Stiripentol.Approved
SufentanilSufentanil may increase the bradycardic activities of Ivabradine.Approved, Investigational
SulfisoxazoleThe serum concentration of Ivabradine can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe serum concentration of Ivabradine can be increased when it is combined with Telaprevir.Withdrawn
TelavancinIvabradine may increase the QTc-prolonging activities of Telavancin.Approved
TelithromycinThe serum concentration of Ivabradine can be increased when it is combined with Telithromycin.Approved
TetrabenazineIvabradine may increase the QTc-prolonging activities of Tetrabenazine.Approved
ThioridazineIvabradine may increase the QTc-prolonging activities of Thioridazine.Withdrawn
TiclopidineThe serum concentration of Ivabradine can be increased when it is combined with Ticlopidine.Approved
TimololTimolol may increase the bradycardic activities of Ivabradine.Approved
TizanidineTizanidine may increase the bradycardic activities of Ivabradine.Approved
TocilizumabThe serum concentration of Ivabradine can be decreased when it is combined with Tocilizumab.Approved
TofacitinibTofacitinib may increase the bradycardic activities of Ivabradine.Approved, Investigational
TorasemideTorasemide may increase the arrhythmogenic activities of Ivabradine.Approved
ToremifeneIvabradine may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
TrichlormethiazideTrichlormethiazide may increase the arrhythmogenic activities of Ivabradine.Approved, Vet Approved
VandetanibIvabradine may increase the QTc-prolonging activities of Vandetanib.Approved
VemurafenibIvabradine may increase the QTc-prolonging activities of Vemurafenib.Approved
VenlafaxineThe serum concentration of Ivabradine can be increased when it is combined with Venlafaxine.Approved
VerapamilVerapamil may increase the bradycardic activities of Ivabradine.Approved
VoriconazoleThe serum concentration of Ivabradine can be increased when it is combined with Voriconazole.Approved, Investigational
ZiprasidoneThe serum concentration of Ivabradine can be increased when it is combined with Ziprasidone.Approved
ZuclopenthixolIvabradine may increase the QTc-prolonging activities of Zuclopenthixol.Approved, Investigational
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.

References

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]
External Links
KEGG Drug
D07165
PubChem Compound
132999
PubChem Substance
310265010
ChemSpider
117373
BindingDB
50326992
ChEBI
85966
ChEMBL
CHEMBL471737
PharmGKB
PA166123415
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ivabradine
ATC Codes
C01EB17 — Ivabradine
AHFS Codes
  • 24:04.92 — Miscellaneous Cardiac Drugs
FDA label
Download (1.45 MB)
MSDS
Download (23.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Individuals1
1, 2RecruitingTreatmentDecompensated Heart Failure1
2CompletedNot AvailableCongestive Heart Failure (CHF)1
2RecruitingTreatmentAngina Pectoris1
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 Failure, Unspecified1
3CompletedTreatmentInappropriate Sinus Tachycardia1
3CompletedTreatmentMitral Valve Stenosis1
3Not Yet RecruitingTreatmentDiabetic Kidney Disease1
3RecruitingTreatmentAging / Healthy Volunteers / Vascular Stiffness1
3RecruitingTreatmentPostural Orthostatic Tachycardia Syndrome (POTS)1
4CompletedTreatmentAsthma, Chronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentCardiac Failure1
4CompletedTreatmentCoronary Artery Disease1
4CompletedTreatmentHeart Failure, Unspecified1
4RecruitingBasic ScienceDilated Cardiomyopathies, Idiopathic / Electrical Remodeling / Heart Failure, Systolic / Ventricular Remodelling1
4RecruitingTreatmentHeart Failure, Unspecified1
4SuspendedTreatmentAnginal Pain / Coronary Artery Disease1
4Unknown StatusDiagnosticCoronary Arteriosclerosis / Coronary Artery Disease1
4Unknown StatusDiagnosticCoronary Artery Disease1
4Unknown StatusTreatmentAcute Coronary Syndromes (ACS)1
4Unknown StatusTreatmentAnginal Pain / Coronary Heart Disease (CHD) / Hemodialysis-dependent patients1
4Unknown StatusTreatmentHeart Failure, Unspecified2
4Unknown StatusTreatmentHigh Heart Rate1
4WithdrawnBasic ScienceBlood Pressures1
4WithdrawnBasic ScienceCentral Arterial Pressure1
Not AvailableCompletedNot AvailableCardiac Failure With Sinus Rhythm or Atrial Fibrillation / Heart Failure, Unspecified / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedNot AvailableHeart Failure, Unspecified1
Not AvailableCompletedTreatmentChronic Liver Diseases (CLD) / Diastolic Dysfunction1
Not AvailableCompletedTreatmentCoronary Artery Disease1
Not AvailableRecruitingTreatmentChronic Heart Failure (CHF)1
Not AvailableUnknown StatusTreatmentChronic Heart Failure (CHF) / Nonvalvular Atrial Fibrillation / Sinus Arrhythmia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral7.5 mg/1
Tablet, film coatedOral5 mg
Tablet, film coatedOral7.5 mg
TabletOral5 mg
TabletOral7.5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7879842No2006-02-222026-02-22Us
US7361650No2006-04-142026-04-14Us
US7867996No2006-02-222026-02-22Us
US7361649No2006-04-172026-04-17Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0202 mg/mLALOGPS
logP3.17ALOGPS
logP2.72ChemAxon
logS-4.4ALOGPS
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
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
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

Taxonomy

Description
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).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Not Available
Direct Parent
Benzazepines
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
Substituents
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)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
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
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  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 October 23, 2017 14:13