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

Stem definition	Drug id	CAS RN
beta-adrenoreceptor antagonists	1887	118457-14-0

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
5	mg	O

ADMET properties:

Property	Value	Reference
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.35 µM/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:

Date	Agency	Company	Orphan
Dec. 17, 2007	FDA	FOREST LABS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (acidic/basic)
pKa1	7.87	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent 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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Beta-2 adrenergic receptor	GPCR	P07550	ADRB2_HUMAN	ANTAGONIST	Ki	7.50	WOMBAT-PK	CHEMBL
Beta-1 adrenergic receptor	GPCR	P08588	ADRB1_HUMAN	ANTAGONIST	Ki	8.50	WOMBAT-PK	CHEMBL
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN		Ki	8	WOMBAT-PK

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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