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: ONP

  • 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 470.79 17.93 454 7526 471758 52869328
Photopsia 149.79 17.93 46 7934 4389 53336697
Drug interaction 137.07 17.93 166 7814 219163 53121923
Torsade de pointes 127.59 17.93 54 7926 12951 53328135
Electrocardiogram QT prolonged 117.85 17.93 84 7896 56319 53284767
Bradycardia 100.62 17.93 84 7896 70972 53270114
Cardiac failure 98.46 17.93 90 7890 85754 53255332
First trimester pregnancy 72.21 17.93 10 7970 8 53341078
Palpitations 69.53 17.93 81 7899 102267 53238819
Syncope 63.66 17.93 81 7899 111912 53229174
Ischaemic stroke 54.99 17.93 34 7946 17959 53323127
Cardiac failure chronic 54.19 17.93 21 7959 4009 53337077
Crush syndrome 52.30 17.93 10 7970 122 53340964
Myoglobin blood increased 48.47 17.93 15 7965 1465 53339621
Ventricular tachycardia 47.87 17.93 31 7949 17731 53323355
Chest pain 47.07 17.93 94 7886 190091 53150995
Congestive cardiomyopathy 45.67 17.93 21 7959 6117 53334969
Apallic syndrome 45.66 17.93 12 7968 651 53340435
Ventricular fibrillation 45.48 17.93 26 7954 11899 53329187
Language disorder 44.71 17.93 15 7965 1896 53339190
Drug effective for unapproved indication 43.82 17.93 15 7965 2015 53339071
Dizziness 43.36 17.93 138 7842 372121 52968965
Acute kidney injury 43.17 17.93 108 7872 253760 53087326
Bundle branch block left 43.00 17.93 21 7959 6992 53334094
Sensorimotor disorder 39.08 17.93 10 7970 488 53340598
Pain 38.67 17.93 20 7960 588378 52752708
Heart rate decreased 37.05 17.93 36 7944 36911 53304175
Tachycardia 36.24 17.93 61 7919 108151 53232935
Rheumatoid arthritis 35.91 17.93 3 7977 314528 53026558
Sinus bradycardia 35.74 17.93 24 7956 14577 53326509
Dyspnoea 34.80 17.93 176 7804 586056 52755030
Angina pectoris 32.64 17.93 30 7950 28695 53312391
Heart rate increased 32.47 17.93 50 7930 82265 53258821
Pneumobilia 32.11 17.93 7 7973 169 53340917
Genital rash 29.26 17.93 8 7972 505 53340581
Hyperparathyroidism secondary 28.29 17.93 10 7970 1477 53339609
Mitral valve incompetence 27.39 17.93 23 7957 19528 53321558
Shock haemorrhagic 27.16 17.93 17 7963 9166 53331920
Drug ineffective 26.11 17.93 52 7928 817193 52523893
Hyperphosphataemia 24.70 17.93 10 7970 2139 53338947
Lactic acidosis 24.44 17.93 29 7951 37224 53303862
Visual impairment 24.26 17.93 41 7939 72871 53268215
Anaemia folate deficiency 24.09 17.93 6 7974 262 53340824
Sinus tachycardia 23.68 17.93 23 7957 23549 53317537
Second trimester pregnancy 23.42 17.93 3 7977 0 53341086
Third trimester pregnancy 23.42 17.93 3 7977 0 53341086
Lordosis 23.13 17.93 6 7974 309 53340777
Hypotension 22.38 17.93 86 7894 253990 53087096
Tuberculosis of central nervous system 21.94 17.93 6 7974 379 53340707
Gastrointestinal tract adenoma 21.92 17.93 6 7974 380 53340706
Femoral neck fracture 21.04 17.93 14 7966 8369 53332717
Atrial tachycardia 20.79 17.93 9 7971 2275 53338811
Cardiac arrest 20.42 17.93 44 7936 93623 53247463
Alopecia 20.40 17.93 5 7975 234578 53106508
Lupus myocarditis 20.09 17.93 4 7976 61 53341025
Pneumonia fungal 20.06 17.93 11 7969 4645 53336441
Orthopnoea 19.83 17.93 12 7968 6092 53334994
Oliguria 19.81 17.93 14 7966 9224 53331862
Serotonin syndrome 19.75 17.93 22 7958 26384 53314702
Osteochondrosis 19.50 17.93 7 7973 1081 53340005
Sinus arrest 19.22 17.93 8 7972 1836 53339250
Nasopharyngitis 19.02 17.93 3 7977 192292 53148794
Gastric antral vascular ectasia 19.02 17.93 6 7974 624 53340462
Personality disorder 18.46 17.93 10 7970 4121 53336965
Arrhythmia 18.37 17.93 25 7955 36754 53304332
Portal hypertensive gastropathy 18.08 17.93 6 7974 733 53340353

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
Cardiac failure 255.59 18.98 201 8144 91472 32413709
Bradycardia 107.57 18.98 111 8234 71451 32433730
Photopsia 102.12 18.98 32 8313 1887 32503294
Cardiac failure chronic 87.80 18.98 41 8304 7199 32497982
Hypotension 84.75 18.98 177 8168 215933 32289248
Computerised tomogram coronary artery abnormal 78.16 18.98 16 8329 158 32505023
Ischaemic cardiomyopathy 67.54 18.98 33 8312 6401 32498780
Sinus bradycardia 60.47 18.98 39 8306 12899 32492282
Dyspnoea 60.04 18.98 216 8129 361829 32143352
Oesophageal obstruction 58.36 18.98 15 8330 428 32504753
N-terminal prohormone brain natriuretic peptide increased 57.15 18.98 21 8324 2011 32503170
Torsade de pointes 54.68 18.98 30 8315 7385 32497796
Bezoar 51.67 18.98 16 8329 906 32504275
Angina pectoris 51.23 18.98 51 8294 31375 32473806
Venous pressure jugular increased 45.26 18.98 14 8331 790 32504391
Blood pressure systolic decreased 45.14 18.98 22 8323 4241 32500940
Hyperkalaemia 42.15 18.98 69 8276 69681 32435500
Base excess decreased 41.43 18.98 10 8335 219 32504962
Dyspnoea at rest 40.65 18.98 19 8326 3340 32501841
Acute kidney injury 40.20 18.98 165 8180 293303 32211878
Drug interaction 39.28 18.98 134 8211 218051 32287130
Brain natriuretic peptide increased 39.07 18.98 20 8325 4280 32500901
Blood potassium increased 38.51 18.98 33 8312 16771 32488410
Oxygen consumption decreased 38.16 18.98 9 8336 178 32505003
Glomerular filtration rate decreased 37.46 18.98 29 8316 12782 32492399
Ejection fraction decreased 37.10 18.98 33 8312 17625 32487556
Ventricular extrasystoles 36.87 18.98 28 8317 11998 32493183
Venous pressure jugular decreased 35.74 18.98 7 8338 54 32505127
Dermatitis exfoliative generalised 34.85 18.98 17 8328 3284 32501897
Ventricular arrhythmia 33.23 18.98 19 8326 5060 32500121
Sinus arrest 31.99 18.98 13 8332 1631 32503550
Urticaria chronic 31.82 18.98 7 8338 100 32505081
Atrial tachycardia 31.67 18.98 14 8331 2163 32503018
Left ventricular enlargement 30.91 18.98 10 8335 653 32504528
Death 29.46 18.98 33 8312 382484 32122697
Oedema peripheral 28.84 18.98 79 8266 114012 32391169
Electrocardiogram abnormal 27.98 18.98 20 8325 7810 32497371
Ventricular dysfunction 27.18 18.98 15 8330 3731 32501450
ECG signs of myocardial ischaemia 26.90 18.98 7 8338 210 32504971
Asthma-chronic obstructive pulmonary disease overlap syndrome 26.75 18.98 10 8335 1004 32504177
Blood creatinine increased 26.75 18.98 69 8276 96063 32409118
Left ventricular dilatation 26.27 18.98 9 8336 702 32504479
Hypertrophy 26.24 18.98 8 8337 430 32504751
Presyncope 26.21 18.98 27 8318 17274 32487907
Tracheal atresia 24.68 18.98 4 8341 8 32505173
Ventricular fibrillation 24.41 18.98 26 8319 17284 32487897
Syncope 24.36 18.98 64 8281 90060 32415121
Cardiomyopathy 24.27 18.98 25 8320 15988 32489193
Ventricular tachycardia 23.74 18.98 31 8314 25525 32479656
Mean cell haemoglobin decreased 23.70 18.98 10 8335 1380 32503801
Tricuspid valve incompetence 22.84 18.98 19 8326 9268 32495913
Congestive cardiomyopathy 22.58 18.98 17 8328 7185 32497996
Bronchial hyperreactivity 22.45 18.98 10 8335 1572 32503609
Large cell lung cancer metastatic 22.26 18.98 4 8341 18 32505163
Low cardiac output syndrome 21.99 18.98 7 8338 434 32504747
Blood chloride increased 21.74 18.98 12 8333 2987 32502194
Pulmonary oedema 21.73 18.98 41 8304 46226 32458955
Oesophageal haemorrhage 21.64 18.98 9 8336 1198 32503983
Lichenoid keratosis 21.35 18.98 11 8334 2385 32502796
Blood luteinising hormone increased 21.34 18.98 5 8340 96 32505085
Eosinophilia 21.23 18.98 29 8316 24929 32480252
Heart rate decreased 21.01 18.98 29 8316 25171 32480010
Contraindicated product administered 20.68 18.98 25 8320 19051 32486130
Cardiac hypertrophy 20.50 18.98 8 8337 903 32504278
Diastolic dysfunction 20.19 18.98 14 8331 5210 32499971
Blood follicle stimulating hormone increased 19.90 18.98 5 8340 130 32505051
Pulmonary function test abnormal 19.81 18.98 10 8335 2076 32503105
Carbon dioxide decreased 19.70 18.98 9 8336 1500 32503681
Off label use 19.63 18.98 140 8205 306180 32199001
Pancreatitis chronic 19.14 18.98 10 8335 2230 32502951
Haemodynamic test abnormal 18.98 18.98 4 8341 46 32505135

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
MeSH PA D002317 Cardiovascular Agents
FDA EPC N0000191544 Hyperpolarization-activated Cyclic Nucleotide-gated Channel Blocker
FDA MoA N0000191546 Hyperpolarization-activated Cyclic Nucleotide-gated Channel Antagonists
CHEBI has role CHEBI:38147 cardiotonic drugs

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 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 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 7879842 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 Dec. 12, 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 Dec. 12, 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 Dec. 12, 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
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 1 Ion channel EC50 5.35 CHEMBL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Ion channel EC50 5.34 CHEMBL

External reference:

IDSource
D07165 KEGG_DRUG
148849-67-6 SECONDARY_CAS_RN
4034416 VANDF
C0257190 UMLSCUI
CHEBI:85969 CHEBI
CHEMBL471737 ChEMBL_ID
CHEMBL2145077 ChEMBL_ID
D000077550 MESH_DESCRIPTOR_UI
DB09083 DRUGBANK_ID
2357 IUPHAR_LIGAND_ID
7523 INN_ID
3H48L0LPZQ UNII
132999 PUBCHEM_CID
1649479 RXNORM
20884 MMSL
233849 MMSL
d05706 MMSL
011156 NDDF
011157 NDDF
420906000 SNOMEDCT_US
421228002 SNOMEDCT_US
421692002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Corlanor HUMAN PRESCRIPTION DRUG LABEL 1 55513-800 TABLET, FILM COATED 5 mg ORAL NDA 31 sections
Corlanor HUMAN PRESCRIPTION DRUG LABEL 1 55513-810 TABLET, FILM COATED 7.50 mg ORAL NDA 31 sections
Corlanor HUMAN PRESCRIPTION DRUG LABEL 1 55513-813 SOLUTION 5 mg ORAL NDA 31 sections
Corlanor HUMAN PRESCRIPTION DRUG LABEL 1 70518-3309 TABLET, FILM COATED 5 mg ORAL NDA 33 sections