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

Stem definitionDrug idCAS RN
antihypertensives, guanidine derivatives 1343 29110-47-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • guanfacine
  • guanfacine hydrochloride
  • guanfacine HCl
  • guanfacine monohydrochloride
A centrally acting antihypertensive agent with specificity towards ADRENERGIC ALPHA-2 RECEPTORS.
  • Molecular weight: 246.09
  • Formula: C9H9Cl2N3O
  • CLOGP: 1.37
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 3
  • TPSA: 78.97
  • ALOGS: -3.25
  • ROTB: 2
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
3 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 1 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.35 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 81 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 5.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 4.50 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.28 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 15 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Oct. 27, 1986 FDA PROMIUS PHARMA
March 30, 2017 PMDA Shionogi & Co., Ltd.

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
Product substitution issue 121.12 26.60 38 1801 14993 46669230
Aggression 90.83 26.60 34 1805 22710 46661513
Somnolence 55.09 26.60 47 1792 156474 46527749
Impulsive behaviour 51.74 26.60 12 1827 1503 46682720
Psychomotor hyperactivity 40.62 26.60 15 1824 9598 46674625
Suicidal ideation 37.89 26.60 25 1814 56357 46627866
Intentional overdose 37.00 26.60 26 1813 64918 46619305
Bradycardia 36.51 26.60 26 1813 66272 46617951
Product administered to patient of inappropriate age 35.58 26.60 10 1829 2686 46681537
Atrioventricular dissociation 33.12 26.60 6 1833 219 46684004
Abnormal behaviour 32.25 26.60 16 1823 21042 46663181
Educational problem 31.75 26.60 6 1833 277 46683946
Irritability 30.14 26.60 17 1822 28929 46655294
Sinus arrhythmia 27.18 26.60 7 1832 1353 46682870

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
Product substitution issue 323.64 32.41 97 3789 9938 29938654
Aggression 247.34 32.41 112 3774 36795 29911797
Agitation 127.35 32.41 82 3804 53991 29894601
Abnormal behaviour 120.24 32.41 61 3825 25562 29923030
Psychomotor hyperactivity 106.23 32.41 40 3846 8184 29940408
Irritability 99.80 32.41 52 3834 22998 29925594
Tic 98.34 32.41 27 3859 2005 29946587
Drug ineffective 81.57 32.41 152 3734 340235 29608357
Somnolence 66.77 32.41 72 3814 96691 29851901
Impulsive behaviour 63.21 32.41 19 3867 1946 29946646
Educational problem 61.81 32.41 13 3873 306 29948286
Anger 53.62 32.41 27 3859 11093 29937499
Brugada syndrome 53.46 32.41 13 3873 595 29947997
Disturbance in attention 53.03 32.41 34 3852 22095 29926497
Bradycardia 45.54 32.41 49 3837 65477 29883115
Negativism 42.93 32.41 10 3876 380 29948212
Emotional disorder 42.18 32.41 18 3868 5076 29943516
Insomnia 42.12 32.41 56 3830 93280 29855312
Disturbance in social behaviour 42.09 32.41 13 3873 1458 29947134
Sinus bradycardia 41.10 32.41 23 3863 11672 29936920
Product quality issue 38.07 32.41 26 3860 18748 29929844
Anxiety 37.62 32.41 52 3834 89819 29858773
Sinus arrest 37.52 32.41 12 3874 1508 29947084
Drug dose titration not performed 36.20 32.41 8 3878 239 29948353
Affective disorder 36.09 32.41 14 3872 3094 29945498
Attention deficit hyperactivity disorder 35.37 32.41 12 3874 1812 29946780
Product administered to patient of inappropriate age 35.11 32.41 13 3873 2530 29946062
Defiant behaviour 33.64 32.41 5 3881 12 29948580
Priapism 33.55 32.41 15 3871 4728 29943864

Pharmacologic Action:

SourceCodeDescription
ATC C02AC02 CARDIOVASCULAR SYSTEM
ANTIHYPERTENSIVES
ANTIADRENERGIC AGENTS, CENTRALLY ACTING
Imidazoline receptor agonists
FDA MoA N0000009918 Adrenergic alpha2-Agonists
FDA EPC N0000175554 Central alpha-2 Adrenergic Agonist
MeSH PA D018663 Adrenergic Agents
MeSH PA D000322 Adrenergic Agonists
MeSH PA D058647 Adrenergic alpha-2 Receptor Agonists
MeSH PA D000316 Adrenergic alpha-Agonists
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D018377 Neurotransmitter Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Attention deficit hyperactivity disorder indication 406506008
Constipation contraindication 14760008 DOID:2089
Myocardial infarction contraindication 22298006 DOID:5844
Alcohol intoxication contraindication 25702006
Orthostatic hypotension contraindication 28651003
Dehydration contraindication 34095006
Depressive disorder contraindication 35489007
Low blood pressure contraindication 45007003
End stage renal disease contraindication 46177005 DOID:784
Bradycardia contraindication 48867003
Cerebrovascular disease contraindication 62914000 DOID:6713
Heart block contraindication 233916004
Disease of liver contraindication 235856003 DOID:409
Syncope contraindication 271594007
Drowsy contraindication 271782001
Chronic myocardial ischemia contraindication 413844008 DOID:3393

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.71 acidic
pKa2 8.15 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Alpha-2A adrenergic receptor GPCR AGONIST EC50 7.16 WOMBAT-PK DRUG LABEL
5-hydroxytryptamine receptor 2A GPCR Ki 6.06 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 5.87 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 6.12 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 6.26 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR AGONIST EC50 5.93 WOMBAT-PK
Nischarin Membrane receptor Ki 7.72 CHEMBL
Alpha-2C adrenergic receptor GPCR AGONIST EC50 5.68 WOMBAT-PK
Alpha-1A adrenergic receptor GPCR IC50 5.87 CHEMBL

External reference:

IDSource
4019771 VUID
N0000147862 NUI
D00606 KEGG_DRUG
29110-48-3 SECONDARY_CAS_RN
4019438 VANDF
4019771 VANDF
C0079466 UMLSCUI
CHEBI:5558 CHEBI
CHEMBL862 ChEMBL_ID
CHEMBL1200494 ChEMBL_ID
DB01018 DRUGBANK_ID
D016316 MESH_DESCRIPTOR_UI
522 IUPHAR_LIGAND_ID
3999 INN_ID
30OMY4G3MK UNII
3519 PUBCHEM_CID
203142 RXNORM
4809 MMSL
521 MMSL
6549 MMSL
d00717 MMSL
000650 NDDF
004497 NDDF
108553003 SNOMEDCT_US
108554009 SNOMEDCT_US
372507007 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0093-5960 TABLET, EXTENDED RELEASE 1 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0093-5961 TABLET, EXTENDED RELEASE 2 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0093-5963 TABLET, EXTENDED RELEASE 3 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0093-5964 TABLET, EXTENDED RELEASE 4 mg ORAL ANDA 28 sections
guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0228-2850 TABLET, EXTENDED RELEASE 1 mg ORAL ANDA 28 sections
guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0228-2851 TABLET, EXTENDED RELEASE 2 mg ORAL ANDA 28 sections
guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0228-2853 TABLET, EXTENDED RELEASE 3 mg ORAL ANDA 28 sections
guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0228-2855 TABLET, EXTENDED RELEASE 4 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0591-0444 TABLET 1 mg ORAL ANDA 24 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0591-0453 TABLET 2 mg ORAL ANDA 24 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17856-0711 TABLET 1 mg ORAL ANDA 13 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 24658-730 TABLET 1 mg ORAL ANDA 24 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 24658-731 TABLET 2 mg ORAL ANDA 24 sections
Guanfacine Extended-Release HUMAN PRESCRIPTION DRUG LABEL 1 24979-533 TABLET, EXTENDED RELEASE 1 mg ORAL ANDA 27 sections
Guanfacine Extended-Release HUMAN PRESCRIPTION DRUG LABEL 1 24979-534 TABLET, EXTENDED RELEASE 2 mg ORAL ANDA 27 sections
Guanfacine Extended-Release HUMAN PRESCRIPTION DRUG LABEL 1 24979-536 TABLET, EXTENDED RELEASE 3 mg ORAL ANDA 27 sections
Guanfacine Extended-Release HUMAN PRESCRIPTION DRUG LABEL 1 24979-538 TABLET, EXTENDED RELEASE 4 mg ORAL ANDA 27 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 29300-458 TABLET 1 mg ORAL ANDA 21 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 29300-459 TABLET 2 mg ORAL ANDA 21 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-310 TABLET 1 mg ORAL ANDA 20 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-311 TABLET 2 mg ORAL ANDA 20 sections
guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 42291-324 TABLET, EXTENDED RELEASE 1 mg ORAL ANDA 29 sections
guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 42291-325 TABLET, EXTENDED RELEASE 2 mg ORAL ANDA 29 sections
guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 42291-326 TABLET, EXTENDED RELEASE 3 mg ORAL ANDA 29 sections
guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 42291-327 TABLET, EXTENDED RELEASE 4 mg ORAL ANDA 29 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 42806-048 TABLET 1 mg ORAL ANDA 24 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 42806-296 TABLET 2 mg ORAL ANDA 24 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50090-4119 TABLET 1 mg ORAL ANDA 14 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50268-373 TABLET 1 mg ORAL ANDA 13 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50268-374 TABLET 2 mg ORAL ANDA 13 sections