ivabradine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
bradycardic agents 3312 155974-00-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • corlanor
  • corlentor
  • ivabradine hydrochloride
  • ivabradine
  • coraxan
  • procoralan
  • ivabradine HCl
Ivabradine is a pure heart rate lowering agent, acting by selective and specific inhibition of the cardiac pacemaker If current that controls the spontaneous diastolic depolarisation in the sinus node and regulates heart rate. The cardiac effects are specific to the sinus node with no effect on intra-atrial, atrioventricular or intraventricular conduction times, nor on myocardial contractility or ventricular repolarisation.
  • Molecular weight: 468.59
  • Formula: C27H36N2O5
  • CLOGP: 3.27
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 0
  • TPSA: 60.47
  • ALOGS: -4.36
  • ROTB: 10

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
10 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 4 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.46 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 1.66 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 10.27 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.28 % Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 20, 2019 PMDA Ono Pharmaceutical Co., Ltd.
April 15, 2015 FDA AMGEN INC
Oct. 25, 2005 EMA Les Laboratoires Servier

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Off label use 1208.97 54.73 330 570 73268 2283917
Bradycardia 207.75 54.73 56 844 9925 2347260
Photopsia 207.69 54.73 37 863 928 2356257
Electrocardiogram QT prolonged 163.09 54.73 44 856 7770 2349415
Dizziness 135.23 54.73 64 836 58601 2298584
Torsade de pointes 120.17 54.73 27 873 2219 2354966
Chest pain 118.16 54.73 47 853 28090 2329095
Ischaemic stroke 109.06 54.73 27 873 3370 2353815
Dyspnoea 103.57 54.73 59 841 78674 2278511
Visual impairment 103.47 54.73 34 866 11721 2345464
Heart rate decreased 101.99 54.73 26 874 3650 2353535
Heart rate increased 93.21 54.73 31 869 11074 2346111
Syncope 91.44 54.73 34 866 16841 2340344
Palpitations 77.70 54.73 30 870 16426 2340759
Hypotension 70.01 54.73 34 866 32402 2324783
Headache 66.68 54.73 45 855 80134 2277051
Blood pressure decreased 66.48 54.73 23 877 9213 2347972
Ventricular tachycardia 62.80 54.73 17 883 2994 2354191
Drug interaction 58.19 54.73 29 871 29134 2328051
Malaise 57.91 54.73 36 864 55549 2301636
Tachycardia 56.96 54.73 24 876 16385 2340800

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Off label use 201.04 47.96 81 648 38490 1707562
Cardiac failure 158.22 47.96 51 678 12551 1733501
Photopsia 147.70 47.96 26 703 446 1745606
Bradycardia 121.29 47.96 40 689 10494 1735558
Hypotension 109.22 47.96 49 680 29605 1716447
Bezoar 93.93 47.96 15 714 136 1745916
Oesophageal obstruction 91.78 47.96 14 715 91 1745961
Dyspnoea 91.18 47.96 52 677 52007 1694045
Chest pain 66.96 47.96 31 698 19883 1726169
Acute kidney injury 66.55 47.96 37 692 34907 1711145
Sinus bradycardia 60.57 47.96 16 713 1917 1744135
Presyncope 59.77 47.96 17 712 2681 1743371
Contraindicated product administered 55.17 47.96 14 715 1430 1744622
Lichenoid keratosis 54.69 47.96 11 718 391 1745661
Dizziness 53.63 47.96 32 697 34329 1711723

Pharmacologic Action:

SourceCodeDescription
ATC C01EB17 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
OTHER CARDIAC PREPARATIONS
Other cardiac preparations
ATC C07FX05 CARDIOVASCULAR SYSTEM
BETA BLOCKING AGENTS
BETA BLOCKING AGENTS, OTHER COMBINATIONS
Beta blocking agents, other combinations
ATC C07FX06 CARDIOVASCULAR SYSTEM
BETA BLOCKING AGENTS
BETA BLOCKING AGENTS, OTHER COMBINATIONS
Beta blocking agents, other combinations
FDA EPC N0000191544 Hyperpolarization-activated Cyclic Nucleotide-gated Channel Blocker
FDA MoA N0000191546 Hyperpolarization-activated Cyclic Nucleotide-gated Channel Antagonists
MeSH PA D002317 Cardiovascular Agents
CHEBI has role CHEBI:38147 cardiotonic drug

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic heart failure indication 48447003
Angina pectoris indication 194828000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.45 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL 7361649 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
EQ 5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL 7361650 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
EQ 5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL 7867996 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
EQ 5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL 7879842 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
EQ 7.5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL 7361649 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
EQ 7.5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL 7361650 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
EQ 7.5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL 7867996 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
EQ 7.5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL 7879842 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL 7361649 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL 7361650 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL 7867996 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL 7879842 Feb. 22, 2026 A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL April 15, 2020 NEW CHEMICAL ENTITY
EQ 7.5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL April 15, 2020 NEW CHEMICAL ENTITY
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL April 15, 2020 NEW CHEMICAL ENTITY
EQ 5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL Oct. 15, 2020 PEDIATRIC EXCLUSIVITY
EQ 7.5MG BASE CORLANOR AMGEN INC N206143 April 15, 2015 RX TABLET ORAL Oct. 15, 2020 PEDIATRIC EXCLUSIVITY
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL Oct. 15, 2020 PEDIATRIC EXCLUSIVITY
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL April 22, 2022 NEW PRODUCT
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL Oct. 22, 2022 PEDIATRIC EXCLUSIVITY
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL April 22, 2026 INDICATED FOR THE TREATMENT OF STABLE SYMPTOMATIC HEART FAILURE DUE TO DILATED CARDIOMYOPATHY (DCM) IN PEDIATRIC PATIENTS AGED 6 MONTHS AND OLDER, WHO ARE IN SINUS RHYTHM WITH AN ELEVATED HEART RATE
5MG/5ML (1MG/ML) CORLANOR AMGEN INC N209964 April 22, 2019 RX SOLUTION ORAL Oct. 22, 2026 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Ion channel BLOCKER IC50 5.70 IUPHAR DRUG LABEL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Ion channel BLOCKER UNKNOWN DRUG LABEL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 Ion channel BLOCKER IC50 5.70 IUPHAR DRUG LABEL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Ion channel EC50 5.37 CHEMBL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Ion channel EC50 5.34 CHEMBL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Ion channel EC50 5.35 CHEMBL

External reference:

IDSource
D000077550 MESH_DESCRIPTOR_UI
C4019965 UMLSCUI
D07165 KEGG_DRUG
3H48L0LPZQ UNII
7523 INN_ID
421692002 SNOMEDCT_US
421228002 SNOMEDCT_US
011156 NDDF
1649480 RXNORM
4034416 VANDF
d05706 MMSL
CHEMBL471737 ChEMBL_ID
148849-67-6 SECONDARY_CAS_RN
DB09083 DRUGBANK_ID
CHEBI:85966 CHEBI
CHEMBL2145077 ChEMBL_ID
132999 PUBCHEM_CID
2357 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Corlanor HUMAN PRESCRIPTION DRUG LABEL 1 55513-800 TABLET, FILM COATED 5 mg ORAL NDA 19 sections
Corlanor HUMAN PRESCRIPTION DRUG LABEL 1 55513-810 TABLET, FILM COATED 7.50 mg ORAL NDA 19 sections
Corlanor HUMAN PRESCRIPTION DRUG LABEL 1 55513-813 SOLUTION 5 mg ORAL NDA 19 sections