Identification

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Name
Nebivolol
Accession Number
DB04861
Type
Small Molecule
Groups
Approved, Investigational
Description

Nebivolol is a racemic mixture of 2 enantiomers where one is a beta adrenergic antagonist and the other acts as a cardiac stimulant without beta adrenergic activity.2 Treatment with nebivolol leads to a greater decrease in systolic and diastolic blood pressure than atenolol, propranolol, or pindolol.2 Nebivolol and other beta blockers are generally not first line therapies as many patients are first treated with thiazide diuretics.[A182594]

Nebivolol was granted FDA approval on 17 December 2007.8

Structure
Thumb
Synonyms
  • Narbivolol
  • Nebivolol
  • Nebivololum
External IDs
PI-21858 / R-65824 / R65,824
Product Ingredients
IngredientUNIICASInChI Key
Nebivolol hydrochlorideJGS34J7L9I152520-56-4JWEXHQAEWHKGCW-VCVZPGOSSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BystolicTablet5 mgOralAllergan2013-04-02Not applicableCanada
BystolicTablet5 mg/1OralCardinal Health2008-01-22Not applicableUs55154 462120180913 8702 15cf2gv
BystolicTablet5 mg/1OralAvera McKennan Hospital2015-03-192018-06-08Us69189 140520180907 15195 1qisxa7
BystolicTablet5 mg/1OralMed Pharma Co., Ltd.2011-06-012012-06-21Us
BystolicTablet2.5 mgOralAllergan2013-04-02Not applicableCanada
BystolicTablet10 mg/1OralA-S Medication Solutions2008-01-22Not applicableUs50090 130720180913 8702 3ph42
BystolicTablet5 mg/1OralA-S Medication Solutions2008-01-22Not applicableUs54569 611920180907 15195 cxsndv
BystolicTablet2.5 mg/1OralMed Pharma Co., Ltd.2011-06-012012-06-21Us
BystolicTablet5 mg/1OralAllergan, Inc.2008-01-22Not applicableUs0456 140520180907 15195 c8ricb
BystolicTablet5 mg/1OralA-S Medication Solutions2008-01-222016-09-27Us50090 112720180913 8702 fyvf8e
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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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NebivololTablet20 mg/1OralAmerigen Pharmaceuticals Inc.2015-04-28Not applicableUs
NebivololTablet10 mg/1OralAmerigen Pharmaceuticals Inc.2015-04-28Not applicableUs
NebivololTablet5 mg/1OralAmerigen Pharmaceuticals Inc.2015-04-28Not applicableUs
NebivololTablet2.5 mg/1OralAmerigen Pharmaceuticals Inc.2015-04-28Not applicableUs
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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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ByvalsonNebivolol hydrochloride (5 mg/1) + Valsartan (80 mg/1)Tablet, film coatedOralAllergan, Inc.2016-06-03Not applicableUs
International/Other Brands
Lobivon / Nebicard / Nebilet / Nebilong / Nodon / Nubeta
Categories
UNII
030Y90569U
CAS number
118457-14-0
Weight
Average: 405.435
Monoisotopic: 405.175164703
Chemical Formula
C22H25F2NO4
InChI Key
KOHIRBRYDXPAMZ-UHFFFAOYSA-N
InChI
InChI=1S/C22H25F2NO4/c23-15-3-7-19-13(9-15)1-5-21(28-19)17(26)11-25-12-18(27)22-6-2-14-10-16(24)4-8-20(14)29-22/h3-4,7-10,17-18,21-22,25-27H,1-2,5-6,11-12H2
IUPAC Name
1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-{[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl]amino}ethan-1-ol
SMILES
OC(CNCC(O)C1CCC2=C(O1)C=CC(F)=C2)C1CCC2=C(O1)C=CC(F)=C2

Pharmacology

Indication

Nebivolol is indicated to treat hypertension.1,2,8,9

Associated Conditions
Pharmacodynamics

Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function.2,3 It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily.2,8 Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease.8 Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.8

Mechanism of action

Nebivolol is a highly selective beta-1 adrenergic receptor antagonist2 with weak beta-2 adrenergic receptor antagonist activity.3 Blocking beta-1 adrenergic receptors by d-nebivolol leads to decreased resting heart rate, exercise heart rate, myocardial contracility, systolic blood pressure, and diastolic blood pressure.4,2,3,5 The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity.5 Nebivolol also inhibits aldosterone, and beta-1 antagonism in the juxtaglomerular apparatus also inhibits the release of renin.5 Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction.5 l-nebivolol is responsible for beta-3 adrenergic receptor agonist activity that stimulates endothelial nitric oxide synthase, increasing nitric oxide levels; leading to vasodilation, decreased peripheral vascular resistance, increased stroke volume, ejection fraction, and cardiac output.1,4,2,3,5 The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients.4

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Humans
UBeta-2 adrenergic receptor
antagonist
Humans
UBeta-3 adrenergic receptor
agonist
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

The absorption of nebivolol is not affected by food.8 Nebivolol has a Tmax of 1.5-4 hours.8 Bioavailability can range from 12-96% for extensive to poor CYP2D6 metabolizers.6,7 For a 20mg dose, d-nebivolol has a Cmax of 2.75±1.55ng/mL, l-nebivolol has a Cmax of 5.29±2.06ng/mL, both enantiomers have a Cmax of 8.02±3.47ng/mL, and nebivolol glucuronides have a Cmax of 68.34±44.68ng/mL.6 For a 20mg dose, d-nebivolol has an AUC of 13.78±15.27ng*h/mL, l-nebivolol has an AUC of 27.72±15.32ng*h/mL, both enantiomers have an AUC of 41.50±29.76ng*h/mL, and nebivolol glucuronides have an AUC of 396.78±297.94ng*h/mL.6

Volume of distribution

For a 20mg dose, d-nebivolol has an apparent volume of distribution of 10,290.81±3911.72L, l-nebivolol has an apparent volume of distribution of 8,066.66±4,055.50L, and both enantiomers together have a volume of distribution of 10,423.42±6796.50L.6

Protein binding

Nebivolol is 98% bound to plasma proteins, mostly to serum albumin.8

Metabolism

Nebivolol is metabolized mainly by glucuronidation and CYP2D6 mediated hydroxylation.1,4 Metabolism involves n-dealkylation, hydroxylation, oxidation, and glucuronidation.7 Aromatic hydroxyl and acyclic oxide metabolites are active, while n-dealkylated and glucuronides are inactive.7

Route of elimination

In extensive CYP2D6 metabolizers, 38% is eliminated in the urine and 44% in the feces.8 In poor CYP2D6 metabolizers, 67% is eliminated in the urine and 13% in the feces.8 <1% of a dose is excreted as the unmetabolized drug.5

Half life

d-nebivolol has a half life of 12 hours in CYP2D6 extensive metabolizers and 19 hours in poor metabolizers.5,8

Clearance

For a 20mg dose, the clearance of d-nebivolol is 1241.63±749.77L/h, l-nebivolol is 435.53±180.93L/h, and both enantiomers is 635.31±300.25L/h.6

Toxicity

Patients experiencing an overdose may present with bradycardia, hypotension, cardiac failure, dizziness, hypoglycemia, fatigue, vomiting, bronchospasm and heart block.8 Treat overdose with general supportive measures including intravenous atropine for bradycardia, vasopressors and intravenous fluids for hypotension, isoproterenol infusion for heart block, digitalis glycosides and diuretics for congestive heart failure, bronchodilators for bronchospasm, and intravenous glucose for hypoglycemia.8

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Nebivolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details

Interactions

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.
DrugInteraction
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Nebivolol can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may decrease the antihypertensive activities of Nebivolol.
1-benzylimidazole1-benzylimidazole may decrease the antihypertensive activities of Nebivolol.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Nebivolol.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Nebivolol.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of Nebivolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of Nebivolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
25-desacetylrifapentineThe metabolism of Nebivolol can be increased when combined with 25-desacetylrifapentine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Nebivolol is combined with 3-isobutyl-1-methyl-7H-xanthine.
4-Bromo-2,5-dimethoxyamphetamineThe therapeutic efficacy of Nebivolol can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
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  • Evidence Level
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  • Action
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Food Interactions
Not Available

References

Synthesis Reference

Thomas Bader, Alfred Stutz, Harald Hofmeier, Hans-Ulrich Bichsel, "Process for preparation of racemic Nebivolol." U.S. Patent US20070149612, issued June 28, 2007.

US20070149612
General References
  1. Gielen W, Cleophas TJ, Agrawal R: Nebivolol: a review of its clinical and pharmacological characteristics. Int J Clin Pharmacol Ther. 2006 Aug;44(8):344-57. [PubMed:16961165]
  2. De Cree J, Cobo C, Geukens H, Verhaegen H: Comparison of the subacute hemodynamic effects of atenolol, propranolol, pindolol, and nebivolol. Angiology. 1990 Feb;41(2):95-105. doi: 10.1177/000331979004100202. [PubMed:1968323]
  3. Van de Water A, Janssens W, Van Neuten J, Xhonneux R, De Cree J, Verhaegen H, Reneman RS, Janssen PA: Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist. J Cardiovasc Pharmacol. 1988 May;11(5):552-63. doi: 10.1097/00005344-198805000-00007. [PubMed:2455841]
  4. Fongemie J, Felix-Getzik E: A Review of Nebivolol Pharmacology and Clinical Evidence. Drugs. 2015 Aug;75(12):1349-71. doi: 10.1007/s40265-015-0435-5. [PubMed:26177892]
  5. Giles TD, Cockcroft JR, Pitt B, Jakate A, Wright HM: Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data. J Hypertens. 2017 Sep;35(9):1758-1767. doi: 10.1097/HJH.0000000000001412. [PubMed:28509722]
  6. Chen CL, Desai-Krieger D, Ortiz S, Kerolous M, Wright HM, Ghahramani P: A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State. Am J Ther. 2015 Sep-Oct;22(5):e130-40. doi: 10.1097/MJT.0000000000000247. [PubMed:25853236]
  7. Briciu C, Neag M, Muntean D, Bocsan C, Buzoianu A, Antonescu O, Gheldiu AM, Achim M, Popa A, Vlase L: Phenotypic differences in nebivolol metabolism and bioavailability in healthy volunteers. Clujul Med. 2015;88(2):208-13. doi: 10.15386/cjmed-395. Epub 2015 Apr 15. [PubMed:26528073]
  8. FDA Approved Drug Products: Nebivolol Tablets [Link]
  9. FDA Approved Drug Products: Nebivolol and Valsartan Tablets [Link]
External Links
Human Metabolome Database
HMDB0015594
KEGG Drug
D05127
PubChem Compound
71301
PubChem Substance
99443225
ChemSpider
64421
BindingDB
84735
ChEBI
64019
ChEMBL
CHEMBL434394
Therapeutic Targets Database
DAP000942
PharmGKB
PA151958426
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Nebivolol
ATC Codes
C09DX05 — Valsartan and nebivololC07FB12 — Nebivolol and amlodipineC07BB12 — Nebivolol and thiazidesC07AB12 — Nebivolol
AHFS Codes
  • 24:24.00 — Beta-adrenergic Blocking Agents
MSDS
Download (69.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceBone, Age-related / Osteoporosis, Age-Related1
0CompletedTreatmentCardiac Steatosis and Lipotoxicity1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentHigh Blood Pressure (Hypertension)2
2CompletedTreatmentHigh Blood Pressure (Hypertension)2
2CompletedTreatmentHypertension,Essential1
2Not Yet RecruitingTreatmentMyocardial Bridging1
2RecruitingTreatmentStroke, Ischemic1
2, 3CompletedPreventionDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
2, 3WithdrawnHealth Services ResearchHigh Blood Pressure (Hypertension)1
3Active Not RecruitingPreventionDuchenne's Muscular Dystrophy (DMD) / Heart Failure / Prophylaxis of cardiomyopathy1
3CompletedTreatmentHigh Blood Pressure (Hypertension)9
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Peripheral Artery Disease (PAD)1
3CompletedTreatmentPrimary Arterial Hypertension1
3CompletedTreatmentStage 1 Hypertension / Stage 2 Hypertension1
3TerminatedTreatmentHigh Blood Pressure (Hypertension)1
3Unknown StatusTreatmentMarfan Syndrome1
4CompletedBasic ScienceMetabolic Syndromes1
4CompletedDiagnosticHigh Blood Pressure (Hypertension)2
4CompletedHealth Services ResearchJNC 7 Stage 1 or 2 Hypertension1
4CompletedOtherHigh Blood Pressure (Hypertension) / Prehypertension2
4CompletedPreventionBlood Pressures / Hypertension Complicated / Left Ventricular Hypertrophy1
4CompletedTreatmentAltitude / Arterial hypoxia / Heart Failure1
4CompletedTreatmentArteriospasm coronary1
4CompletedTreatmentAtherosclerosis / Endothelial Function1
4CompletedTreatmentChronic Heart Failure (CHF)1
4CompletedTreatmentCoronary Artery Disease / High Blood Pressure (Hypertension)1
4CompletedTreatmentHigh Blood Pressure (Hypertension)15
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Left Ventricular Diastolic Dysfunction1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Pre-Hypertension1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedTreatmentMicrovascular Angina1
4CompletedTreatmentStage 2 Diastolic Hypertension1
4Not Yet RecruitingTreatmentAcute Myocardial Infarction (AMI) / Non-ST Elevation Myocardial Infarction (NSTEMI) / ST Elevation Myocardial Infarction1
4RecruitingTreatmentDiastolic Heart Failure / Heart Failure With Preserved Ejection Fraction (HFpEF) / Pulmonary Hypertension (PH)1
4RecruitingTreatmentHeart Diseases / Type 2 Diabetes Mellitus1
4TerminatedTreatmentCoronary Artery Disease1
4TerminatedTreatmentHigh Blood Pressure (Hypertension)2
4Unknown StatusTreatmentEndothelial Dysfunction / High Blood Pressure (Hypertension) / Obstructive Sleep Apnea (OSA)1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension)1
4Unknown StatusTreatmentImpotence1
Not AvailableCompletedNot AvailableHeart Failure / High Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension) / Multiple System Atrophy (MSA) / Progressive autonomic failure1
Not AvailableCompletedDiagnosticArterial Hypertension1
Not AvailableCompletedDiagnosticHigh Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentFemale Sexual Dysfunction (FSD) / High Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension)2
Not AvailableRecruitingNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableRecruitingTreatmentHeart Failure1
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension) / Transplant; Failure, Kidney1
Not AvailableUnknown StatusNot AvailableHeart Failure1
Not AvailableUnknown StatusNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableWithdrawnTreatmentCentral Aortic Pressure1
Not AvailableWithdrawnTreatmentHigh Blood Pressure (Hypertension)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Forest Laboratories Inc.
  • Forest Pharmaceuticals
  • Mylan
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
TabletOral10 mg
TabletOral10 mg/1
TabletOral2.5 mg
TabletOral2.5 mg/1
TabletOral20 mg/1
TabletOral20 mg
TabletOral5 mg
TabletOral5 mg/1
Tablet, film coatedOral
Prices
Unit descriptionCostUnit
Bystolic 10 mg tablet2.09USD tablet
Bystolic 20 mg tablet2.09USD tablet
Bystolic 2.5 mg tablet2.06USD tablet
Bystolic 5 mg tablet2.06USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5759580No1998-06-022015-06-02Us
US6545040No2003-04-082021-12-17Us
US7803838No2010-09-282026-08-29Us
US7838552No2010-11-232027-10-04Us
Additional Data Available
  • Filed On
    Filed On

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

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)223.0-228.0https://www.tcichemicals.com/eshop/en/gb/commodity/N0954/
water solubility0.091g/100mLhttp://www.medicines.org.au/files/txpnebiv.pdf
logP4.183https://www.sigmaaldrich.com/MSDS/MSDS/DisplayMSDSPage.do?country=CA&language=en&productNumber=N1915&brand=SIGMA&PageToGoToURL=https%3A%2F%2Fwww.sigmaaldrich.com%2Fcatalog%2Fproduct%2Fsigma%2Fn1915%3Flang%3Den
pKa8.13http://www.medicines.org.au/files/txpnebiv.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0403 mg/mLALOGPS
logP2.44ALOGPS
logP3.21ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)13.52ChemAxon
pKa (Strongest Basic)8.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area70.95 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity103.32 m3·mol-1ChemAxon
Polarizability41.98 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8483
Blood Brain Barrier+0.7802
Caco-2 permeable-0.5549
P-glycoprotein substrateSubstrate0.7928
P-glycoprotein inhibitor INon-inhibitor0.7443
P-glycoprotein inhibitor IINon-inhibitor0.567
Renal organic cation transporterNon-inhibitor0.8016
CYP450 2C9 substrateNon-substrate0.8738
CYP450 2D6 substrateNon-substrate0.7248
CYP450 3A4 substrateNon-substrate0.6822
CYP450 1A2 substrateInhibitor0.5145
CYP450 2C9 inhibitorNon-inhibitor0.7876
CYP450 2D6 inhibitorNon-inhibitor0.5994
CYP450 2C19 inhibitorNon-inhibitor0.5923
CYP450 3A4 inhibitorNon-inhibitor0.9441
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8336
Ames testNon AMES toxic0.7132
CarcinogenicityNon-carcinogens0.9402
BiodegradationNot ready biodegradable0.9953
Rat acute toxicity2.7228 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5769
hERG inhibition (predictor II)Inhibitor0.8381
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 1-benzopyrans. These are organic aromatic compounds that 1-benzopyran, a bicyclic compound made up of a benzene ring fused to a pyran, so that the oxygen atom is at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzopyrans
Sub Class
1-benzopyrans
Direct Parent
1-benzopyrans
Alternative Parents
Aralkylamines / Alkyl aryl ethers / Benzenoids / Aryl fluorides / Secondary alcohols / 1,2-aminoalcohols / Oxacyclic compounds / Dialkylamines / Organopnictogen compounds / Organofluorides
show 1 more
Substituents
1-benzopyran / Alkyl aryl ether / Aralkylamine / Aryl fluoride / Aryl halide / Benzenoid / 1,2-aminoalcohol / Secondary alcohol / Oxacycle / Secondary amine
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, secondary alcohol, secondary amino compound, diol, chromanes (CHEBI:64019)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Gielen W, Cleophas TJ, Agrawal R: Nebivolol: a review of its clinical and pharmacological characteristics. Int J Clin Pharmacol Ther. 2006 Aug;44(8):344-57. [PubMed:16961165]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. de Boer RA, Voors AA, van Veldhuisen DJ: Nebivolol: third-generation beta-blockade. Expert Opin Pharmacother. 2007 Jul;8(10):1539-50. [PubMed:17661735]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Nuttall SL, Routledge HC, Kendall MJ: A comparison of the beta1-selectivity of three beta1-selective beta-blockers. J Clin Pharm Ther. 2003 Jun;28(3):179-86. [PubMed:12795776]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name
ADRB3
Uniprot ID
P13945
Uniprot Name
Beta-3 adrenergic receptor
Molecular Weight
43518.615 Da
References
  1. Gielen W, Cleophas TJ, Agrawal R: Nebivolol: a review of its clinical and pharmacological characteristics. Int J Clin Pharmacol Ther. 2006 Aug;44(8):344-57. [PubMed:16961165]
  2. Fongemie J, Felix-Getzik E: A Review of Nebivolol Pharmacology and Clinical Evidence. Drugs. 2015 Aug;75(12):1349-71. doi: 10.1007/s40265-015-0435-5. [PubMed:26177892]
  3. De Cree J, Cobo C, Geukens H, Verhaegen H: Comparison of the subacute hemodynamic effects of atenolol, propranolol, pindolol, and nebivolol. Angiology. 1990 Feb;41(2):95-105. doi: 10.1177/000331979004100202. [PubMed:1968323]
  4. Van de Water A, Janssens W, Van Neuten J, Xhonneux R, De Cree J, Verhaegen H, Reneman RS, Janssen PA: Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist. J Cardiovasc Pharmacol. 1988 May;11(5):552-63. doi: 10.1097/00005344-198805000-00007. [PubMed:2455841]
  5. Giles TD, Cockcroft JR, Pitt B, Jakate A, Wright HM: Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data. J Hypertens. 2017 Sep;35(9):1758-1767. doi: 10.1097/HJH.0000000000001412. [PubMed:28509722]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Gielen W, Cleophas TJ, Agrawal R: Nebivolol: a review of its clinical and pharmacological characteristics. Int J Clin Pharmacol Ther. 2006 Aug;44(8):344-57. [PubMed:16961165]
  2. Flockhart Table of Drug Interactions [Link]
  3. FDA Approved Drug Products: Nebivolol Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Hocht C, Bertera FM, Mayer MA, Taira CA: Issues in drug metabolism of major antihypertensive drugs: beta-blockers, calcium channel antagonists and angiotensin receptor blockers. Expert Opin Drug Metab Toxicol. 2010 Feb;6(2):199-211. doi: 10.1517/17425250903397381. [PubMed:20095790]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Hu X, Lan T, Dai D, Xu RA, Yuan L, Zhou Q, Li Y, Cai J, Hu G: Evaluation of 24 CYP2D6 Variants on the Metabolism of Nebivolol In Vitro. Drug Metab Dispos. 2016 Nov;44(11):1828-1831. doi: 10.1124/dmd.116.071811. Epub 2016 Aug 18. [PubMed:27538917]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Nebivolol Tablets [Link]

Drug created on October 19, 2007 15:00 / Updated on November 11, 2019 06:54