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

Stem definitionDrug idCAS RN
beta-adrenoreceptor antagonists 1887 118457-14-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nebivolol
  • nebivolol hydrochloride
  • vasoxen
  • bystolic
  • nebivolol HCl
A cardioselective ADRENERGIC BETA-1 RECEPTOR ANTAGONIST (beta-blocker) that functions as a VASODILATOR through the endothelial L-arginine/ NITRIC OXIDE system. It is used to manage HYPERTENSION and chronic HEART FAILURE in elderly patients.
  • Molecular weight: 405.44
  • Formula: C22H25F2NO4
  • CLOGP: 3.50
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 3
  • TPSA: 70.95
  • ALOGS: -4
  • ROTB: 6

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
5 mg O

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.35 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 11 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 14 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.02 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 17, 2007 FDA FOREST LABS

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
Bradycardia 311.69 31.12 76 760 9905 2347344
Hypotension 157.99 31.12 59 777 32377 2324872
Heart rate decreased 98.94 31.12 25 811 3651 2353598
Dyspnoea 96.73 31.12 55 781 78678 2278571
Oedema peripheral 89.51 31.12 36 800 23727 2333522
Presyncope 78.72 31.12 21 815 3782 2353467
Drug interaction 72.71 31.12 33 803 29130 2328119
Acute kidney injury 70.66 31.12 32 804 28090 2329159
Syncope 54.67 31.12 23 813 16852 2340397
Blood pressure increased 54.52 31.12 23 813 16963 2340286
Completed suicide 52.95 31.12 24 812 21010 2336239
Hypertension 52.86 31.12 26 810 27335 2329914
Orthostatic hypotension 50.66 31.12 14 822 2865 2354384
Drug hypersensitivity 47.46 31.12 29 807 46614 2310635
Hyperkalaemia 44.71 31.12 15 821 5878 2351371
Dizziness 43.75 31.12 30 806 58635 2298614
Fall 42.14 31.12 27 809 47072 2310177
Asthenia 37.32 31.12 25 811 46901 2310348
Cough 37.28 31.12 22 814 33095 2324154
Drug ineffective 36.88 31.12 34 802 101590 2255659
Fatigue 35.93 31.12 31 805 84842 2272407
Headache 35.39 31.12 30 806 80149 2277100
Hyponatraemia 32.83 31.12 15 821 13310 2343939
Palpitations 32.79 31.12 16 820 16440 2340809
Walking disability 31.46 31.12 6 830 234 2357015
Alopecia 31.16 31.12 17 819 21984 2335265

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
Bradycardia 162.70 32.03 48 568 10486 1735679
Hypotension 54.54 32.03 29 587 29625 1716540
Loss of consciousness 53.19 32.03 23 593 14852 1731313
Syncope 50.95 32.03 22 594 14147 1732018
Orthostatic hypotension 49.82 32.03 15 601 3416 1742749
Drug interaction 44.84 32.03 25 591 27933 1718232
Acute kidney injury 44.79 32.03 27 589 34917 1711248
Blood pressure increased 42.94 32.03 18 598 10735 1735430
Dyspnoea 41.79 32.03 30 586 52029 1694136
Heart rate decreased 39.56 32.03 12 604 2797 1743368
Sinus bradycardia 39.37 32.03 11 605 1922 1744243
Cranial sutures widening 38.17 32.03 5 611 10 1746155
Neonatal anuria 36.26 32.03 5 611 17 1746148
Dizziness 35.06 32.03 23 593 34338 1711827
Renal failure 32.29 32.03 18 598 19999 1726166

Pharmacologic Action:

SourceCodeDescription
ATC C07AB12 CARDIOVASCULAR SYSTEM
BETA BLOCKING AGENTS
BETA BLOCKING AGENTS
Beta blocking agents, selective
ATC C07BB12 CARDIOVASCULAR SYSTEM
BETA BLOCKING AGENTS
BETA BLOCKING AGENTS AND THIAZIDES
Beta blocking agents, selective, and thiazides
ATC C07FB12 CARDIOVASCULAR SYSTEM
BETA BLOCKING AGENTS
BETA BLOCKING AGENTS, OTHER COMBINATIONS
Beta blocking agents and calcium channel blockers
ATC C09DX05 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
Angiotensin II receptor blockers (ARBs), other combinations
MeSH PA D018663 Adrenergic Agents
MeSH PA D000322 Adrenergic Agonists
FDA MoA N0000000161 Adrenergic beta-Antagonists
FDA EPC N0000175556 beta-Adrenergic Blocker
MeSH PA D058665 Adrenergic beta-1 Receptor Agonists
MeSH PA D000318 Adrenergic beta-Agonists
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D018377 Neurotransmitter Agents
CHEBI has role CHEBI:35530 beta-adrenergic antagonist
CHEBI has role CHEBI:35620 vasodilator agent
CHEBI has role CHEBI:35674 antihypertensive agent
MeSH PA D014665 Vasodilator Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Chronic heart failure off-label use 48447003
Atrial fibrillation off-label use 49436004 DOID:0060224
Angina pectoris off-label use 194828000
Myocardial Reinfarction Prevention off-label use
Bronchospasm contraindication 4386001
Complete atrioventricular block contraindication 27885002
Sick sinus syndrome contraindication 36083008 DOID:13884
Bradycardia contraindication 48867003
Acute nephropathy contraindication 58574008
Hepatic failure contraindication 59927004
Diabetes mellitus contraindication 73211009 DOID:9351
Cardiogenic shock contraindication 89138009
Second degree atrioventricular block contraindication 195042002
Decompensated cardiac failure contraindication 195111005
Disease of liver contraindication 235856003 DOID:409
Hypoglycemic disorder contraindication 237630007
Peripheral vascular disease contraindication 400047006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.87 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 10MG BASE BYSTOLIC ALLERGAN N021742 Dec. 17, 2007 RX TABLET ORAL 6545040 Dec. 17, 2021 TREATMENT OF HYPERTENSION
EQ 2.5MG BASE BYSTOLIC ALLERGAN N021742 Dec. 17, 2007 RX TABLET ORAL 6545040 Dec. 17, 2021 TREATMENT OF HYPERTENSION
EQ 20MG BASE BYSTOLIC ALLERGAN N021742 Oct. 8, 2008 RX TABLET ORAL 6545040 Dec. 17, 2021 TREATMENT OF HYPERTENSION
EQ 5MG BASE BYSTOLIC ALLERGAN N021742 Dec. 17, 2007 RX TABLET ORAL 6545040 Dec. 17, 2021 TREATMENT OF HYPERTENSION
EQ 5MG BASE BYVALSON ALLERGAN N206302 June 3, 2016 DISCN TABLET ORAL 7838552 Oct. 4, 2027 METHOD OF TREATING HYPERTENSION

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Beta-2 adrenergic receptor GPCR ANTAGONIST Ki 7.50 WOMBAT-PK CHEMBL
Beta-1 adrenergic receptor GPCR ANTAGONIST Ki 8.50 WOMBAT-PK CHEMBL
5-hydroxytryptamine receptor 1A GPCR Ki 8 WOMBAT-PK

External reference:

IDSource
D000068577 MESH_DESCRIPTOR_UI
4027169 VUID
N0000179202 NUI
C0068475 UMLSCUI
D05127 KEGG_DRUG
030Y90569U UNII
5969 INN_ID
318638009 SNOMEDCT_US
d05265 MMSL
4027169 VANDF
31555 RXNORM
395808005 SNOMEDCT_US
007077 NDDF
18486 MMSL
CHEMBL434394 ChEMBL_ID
152520-56-4 SECONDARY_CAS_RN
DB04861 DRUGBANK_ID
CHEBI:64022 CHEBI
CHEMBL1201731 ChEMBL_ID
71301 PUBCHEM_CID
7246 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 0456-1402 TABLET 2.50 mg ORAL NDA 17 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 0456-1405 TABLET 5 mg ORAL NDA 17 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 0456-1410 TABLET 10 mg ORAL NDA 17 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 0456-1420 TABLET 20 mg ORAL NDA 17 sections
Nebivolol HUMAN PRESCRIPTION DRUG LABEL 1 43975-248 TABLET 2.50 mg ORAL ANDA 16 sections
Nebivolol HUMAN PRESCRIPTION DRUG LABEL 1 43975-249 TABLET 5 mg ORAL ANDA 16 sections
Nebivolol HUMAN PRESCRIPTION DRUG LABEL 1 43975-250 TABLET 10 mg ORAL ANDA 16 sections
Nebivolol HUMAN PRESCRIPTION DRUG LABEL 1 43975-251 TABLET 20 mg ORAL ANDA 16 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 50090-1307 TABLET 10 mg ORAL NDA 17 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 50090-3326 TABLET 20 mg ORAL NDA 17 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 54868-5944 TABLET 5 mg ORAL NDA 18 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 54868-6018 TABLET 10 mg ORAL NDA 18 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 55154-4621 TABLET 5 mg ORAL NDA 17 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 55154-4622 TABLET 20 mg ORAL NDA 17 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 55154-4623 TABLET 10 mg ORAL NDA 17 sections
Bystolic HUMAN PRESCRIPTION DRUG LABEL 1 68151-5135 TABLET 10 mg ORAL NDA 17 sections