Details of the Drug

General Information of Drug (ID: DM7F1PA)

• Drug Name: Nebivolol
• Synonyms: Bystolic; Lobivon; Nebilet; Nebilong; Nebipill; Nebivololum; Nubeta; Nebivololum [Latin]; R 67555; Bystolic (TN); Nebicard-5;Nebilet (TN); Nebilong (TN); Nodon (TN); Nubeta (TN); PI-21858; R-67555; R65,824; Nebicard-5 (TN); Nebivolol (USAN/INN); Nebivolol [USAN:INN:BAN]; Alpha,alpha'-(Iminodimethylene)bis(6-fluoro-2-chromanmethanol); Alpha,alpha'-(Iminobis(methylene))bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol); Alpha,alpha'-(iminobis(methylene))bis(6-fluoro-3,4-dihydro)-2H-1-benzopyran-2-methanol; 1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-[[2-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-hydroxyethyl]amino]ethanol; 2,2'-iminobis[1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol]

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[1]

• Therapeutic Class: Antihypertensive Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 405.4
  Logarithm of the Partition Coefficient (xlogp); 3
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.5-4 h [2]
  Bioavailability: The bioavailability of drug is 12-96% [2]
  Clearance: The clearance of drug is 1241.63 +/- 749.77 L/h [3]
  Elimination: In extensive CYP2D6 metabolizers, 38% is eliminated in the urine and 44% in the feces [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 12 hours [4]
  Metabolism: The drug is metabolized via the glucuronidation and CYP2D6 mediated hydroxylation [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.3523 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.02% [7]
  Vd: The volume of distribution (Vd) of drug is 10,290.81 +/- 3,911.72 L [3]
• Chemical Identifiers:
  Formula: C22H25F2NO4
  IUPAC Name: 1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-[[2-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-hydroxyethyl]amino]ethanol
  Canonical SMILES: C1CC2=C(C=CC(=C2)F)OC1C(CNCC(C3CCC4=C(O3)C=CC(=C4)F)O)O
  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
  InChIKey: KOHIRBRYDXPAMZ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 71301
  ChEBI ID: CHEBI:64019
  CAS Number: 99200-09-6
  DrugBank ID: DB04861
  TTD ID: D0Z1UA
  INTEDE ID: DR1134
  ACDINA ID: D00459

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Antagonist	[8]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[9]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[10]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Nebivolol

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Levamlodipine	DM92S6N	Moderate	Increased risk of cardiac depression by the combination of Nebivolol and Levamlodipine.	Hypertension [BA00-BA04]	[11]
Clevidipine butyrate	DMW4M97	Moderate	Increased risk of cardiac depression by the combination of Nebivolol and Clevidipine butyrate.	Hypertension [BA00-BA04]	[11]

Coadministration of a Drug Treating the Disease Different from Nebivolol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cariprazine	DMJYDVK	Moderate	Additive hypotensive effects by the combination of Nebivolol and Cariprazine.	Bipolar disorder [6A60]	[12]
Atracurium	DM42HXN	Moderate	Additive cardiorespiratory depression effects by the combination of Nebivolol and Atracurium.	Corneal disease [9A76-9A78]	[13]
Pasireotide	DMHM7JS	Moderate	Increased risk of atrioventricular block by the combination of Nebivolol and Pasireotide.	Cushing syndrome [5A70]	[14]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Nebivolol and OPC-34712.	Depression [6A70-6A7Z]	[12]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Nebivolol caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[15]
Mirabegron	DMS1GYT	Moderate	Decreased metabolism of Nebivolol caused by Mirabegron mediated inhibition of CYP450 enzyme.	Functional bladder disorder [GC50]	[16]
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Nebivolol caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[17]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Nebivolol caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[18]
Belladonna	DM2RBWK	Moderate	Antagonize the effect of Nebivolol when combined with Belladonna.	Infectious gastroenteritis/colitis [1A40]	[19]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Nebivolol caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[20]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Nebivolol and ITI-007.	Insomnia [7A00-7A0Z]	[12]
Glycerol phenylbutyrate	DMDGRQO	Moderate	Decreased metabolism of Nebivolol caused by Glycerol phenylbutyrate mediated inhibition of CYP450 enzyme.	Liver disease [DB90-DB9Z]	[19]
Dacomitinib	DMOH8VY	Moderate	Decreased metabolism of Nebivolol caused by Dacomitinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[21]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Nebivolol caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[22]
Lanthanum carbonate	DMMJQSH	Moderate	Decreased absorption of Nebivolol due to formation of complexes caused by Lanthanum carbonate.	Mineral absorption/transport disorder [5C64]	[14]
Panobinostat	DM58WKG	Moderate	Decreased metabolism of Nebivolol caused by Panobinostat mediated inhibition of CYP450 enzyme.	Multiple myeloma [2A83]	[23]
Siponimod	DM2R86O	Major	Increased risk of bradycardia by the combination of Nebivolol and Siponimod.	Multiple sclerosis [8A40]	[24]
Fingolimod	DM5JVAN	Major	Increased risk of atrioventricular block by the combination of Nebivolol and Fingolimod.	Multiple sclerosis [8A40]	[25]
Ozanimod	DMT6AM2	Moderate	Increased risk of atrioventricular block by the combination of Nebivolol and Ozanimod.	Multiple sclerosis [8A40]	[26]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Nebivolol caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[19]
Rolapitant	DM8XP26	Moderate	Decreased metabolism of Nebivolol caused by Rolapitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[27]
Lorcaserin	DMG6OYJ	Moderate	Decreased metabolism of Nebivolol caused by Lorcaserin mediated inhibition of CYP450 enzyme.	Obesity [5B80-5B81]	[28]
Methylscopolamine	DM5VWOB	Moderate	Antagonize the effect of Nebivolol when combined with Methylscopolamine.	Peptic ulcer [DA61]	[19]
ABIRATERONE	DM8V75C	Moderate	Decreased metabolism of Nebivolol caused by ABIRATERONE mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[29]
Silodosin	DMJSBT6	Moderate	Additive hypotensive effects by the combination of Nebivolol and Silodosin.	Prostate hyperplasia [GA90]	[30]
Iloperidone	DM6AUFY	Moderate	Additive hypotensive effects by the combination of Nebivolol and Iloperidone.	Schizophrenia [6A20]	[12]
Amisulpride	DMSJVAM	Moderate	Increased risk of ventricular arrhythmias by the combination of Nebivolol and Amisulpride.	Schizophrenia [6A20]	[19]
Asenapine	DMSQZE2	Moderate	Additive hypotensive effects by the combination of Nebivolol and Asenapine.	Schizophrenia [6A20]	[12]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
D&C red no. 27	E00381	83511	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Carmellose sodium	E00625	Not Available	Disintegrant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Nebivolol 10 mg tablet	10 mg	Oral Tablet	Oral
Nebivolol 2.5 mg tablet	2.5 mg	Oral Tablet	Oral
Nebivolol 20 mg tablet	20 mg	Oral Tablet	Oral
Nebivolol 5 mg tablet	5 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7246).
• [2] FDA Approved Drug Products: Nebivolol Tablets
• [3] 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.
• [4] 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.
• [5] Setnikar I, Rovati LC: Absorption, distribution, metabolism and excretion of glucosamine sulfate. A review. Arzneimittelforschung. 2001 Sep;51(9):699-725. doi: 10.1055/s-0031-1300105.
• [6] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [7] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [8] Nitric oxide mechanisms of nebivolol. Ther Adv Cardiovasc Dis. 2009 Aug;3(4):317-27.
• [9] Nebivolol: a review of its clinical and pharmacological characteristics. Int J Clin Pharmacol Ther. 2006 Aug;44(8):344-57.
• [10] Evaluation of 24 CYP2D6 variants on the metabolism of nebivolol in vitro. Drug Metab Dispos. 2016 Nov;44(11):1828-1831.
• [11] Anastassiades CJ "Nifedipine and beta-blocker drugs." Br Med J 281 (1980): 1251-2. [PMID: 6107167]
• [12] Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
• [13] Chapple DJ, Clark JS, Hughes R "Interaction between atracurium and drugs used in anaesthesia." Br J Anaesth 55 Suppl 1 (1983): s17-22. [PMID: 6688011]
• [14] Canadian Pharmacists Association.
• [15] EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
• [16] Product Information. Myrbetriq (mirabegron). Astellas Pharma US, Inc, Deerfield, IL.
• [17] Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov). Gilead Sciences, Foster City, CA.
• [18] Product Information. Givlaari (givosiran). Alnylam Pharmaceuticals, Cambridge, MA.
• [19] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [20] Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
• [21] Product Information. Vizimpro (dacomitinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [22] Product Information. Zelboraf (vemurafenib). Genentech, South San Francisco, CA.
• [23] Product Information. Farydak (panobinostat). Novartis Pharmaceuticals, East Hanover, NJ.
• [24] Cerner Multum, Inc. "Australian Product Information.".
• [25] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [26] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
• [27] Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
• [28] Product Information. Belviq (lorcaserin). Eisai Inc, Teaneck, NJ.
• [29] Product Information. Zytiga (abiraterone). Centocor Inc, Malvern, PA.
• [30] Chrysant SG "Experience with terazosin administered in combination with other antihypertensive agents." Am J Med 80 (1986): 55-61. [PMID: 2872808]