guanfacine ๐Ÿถ Veterinary Use | 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 ยตM/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
March 30, 2017 PMDA Shionogi & Co., Ltd.
Oct. 27, 1986 FDA PROMIUS PHARMA
Sept. 17, 2015 EMA Takeda Pharmaceuticals International AG Ireland Branch

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
Intentional overdose 182.08 26.07 80 2650 74072 63412220
Product substitution issue 119.43 26.07 39 2691 15957 63470335
Aggression 79.76 26.07 32 2698 23466 63462826
Distributive shock 79.26 26.07 17 2713 1366 63484926
Somnolence 77.81 26.07 63 2667 178622 63307670
Bradycardia 72.85 26.07 43 2687 73184 63413108
Impulsive behaviour 66.04 26.07 15 2715 1568 63484724
Bradypnoea 54.01 26.07 15 2715 3535 63482757
Suicidal ideation 50.15 26.07 32 2698 62389 63423903
Abnormal behaviour 48.81 26.07 22 2708 21404 63464888
Psychomotor hyperactivity 48.58 26.07 18 2712 10645 63475647
Intentional self-injury 48.02 26.07 23 2707 25664 63460628
Sinus bradycardia 46.54 26.07 19 2711 14532 63471760
Cerebral disorder 41.85 26.07 13 2717 4513 63481779
Product administered to patient of inappropriate age 41.53 26.07 12 2718 3256 63483036
Hypotension 40.54 26.07 54 2676 272550 63213742
Electrocardiogram QT prolonged 39.28 26.07 27 2703 59503 63426789
Coma 37.38 26.07 27 2703 64337 63421955
Suicide attempt 34.11 26.07 25 2705 60893 63425399
Atrioventricular dissociation 32.57 26.07 6 2724 220 63486072
Irritability 32.48 26.07 19 2711 31675 63454617
Sinus arrhythmia 30.79 26.07 8 2722 1465 63484827
Educational problem 29.06 26.07 6 2724 400 63485892
Overdose 27.33 26.07 29 2701 115049 63371243

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 350.07 32.83 106 4983 9989 34941853
Aggression 300.24 32.83 135 4954 38829 34913013
Psychomotor hyperactivity 148.55 32.83 55 5034 9567 34942275
Agitation 142.59 32.83 94 4995 57305 34894537
Abnormal behaviour 120.69 32.83 63 5026 24906 34926936
Irritability 104.41 32.83 57 5032 24633 34927209
Impulsive behaviour 98.06 32.83 28 5061 2134 34949708
Tic 94.90 32.83 27 5062 2031 34949811
Somnolence 89.97 32.83 95 4994 111021 34840821
Drug ineffective 86.28 32.83 198 4891 456553 34495289
Bradycardia 76.65 32.83 73 5016 75345 34876497
Dystonia 62.96 32.83 31 5058 10814 34941028
Anger 60.28 32.83 31 5058 11853 34939989
Educational problem 52.99 32.83 13 5076 549 34951293
Brugada syndrome 48.41 32.83 13 5076 788 34951054
Electrocardiogram QT prolonged 48.06 32.83 43 5046 40909 34910933
Disturbance in attention 46.80 32.83 35 5054 25910 34925932
Autism spectrum disorder 46.25 32.83 16 5073 2280 34949562
Insomnia 45.14 32.83 65 5024 103842 34848000
Suicidal ideation 44.63 32.83 41 5048 40347 34911495
Product use issue 42.30 32.83 49 5040 63167 34888675
Emotional disorder 41.30 32.83 19 5070 5697 34946145
Negativism 41.07 32.83 10 5079 409 34951433
Attention deficit hyperactivity disorder 40.83 32.83 15 5074 2544 34949298
Product quality issue 40.00 32.83 27 5062 17008 34934834
Sinus bradycardia 38.97 32.83 24 5065 12939 34938903
Sinus arrest 38.47 32.83 13 5076 1727 34950115
Product administered to patient of inappropriate age 37.16 32.83 15 5074 3276 34948566
Distractibility 37.03 32.83 9 5080 365 34951477
Hallucination 36.27 32.83 41 5048 51457 34900385
Defiant behaviour 34.80 32.83 5 5084 7 34951835
Disturbance in social behaviour 33.84 32.83 12 5077 1839 34950003
Affective disorder 33.09 32.83 15 5074 4345 34947497

FDA Adverse Event Reporting System (Geriatric)

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 380.35 24.12 117 6601 20139 79717531
Aggression 350.03 24.12 139 6579 50819 79686851
Psychomotor hyperactivity 173.86 24.12 62 6656 16787 79720883
Intentional overdose 165.92 24.12 106 6612 105854 79631816
Impulsive behaviour 149.09 24.12 37 6681 2863 79734807
Bradycardia 140.03 24.12 105 6613 135452 79602218
Agitation 139.54 24.12 93 6625 99622 79638048
Abnormal behaviour 127.70 24.12 62 6656 36359 79701311
Irritability 117.65 24.12 61 6657 41083 79696587
Somnolence 109.74 24.12 117 6601 238864 79498806
Electrocardiogram QT prolonged 104.51 24.12 75 6643 90311 79647359
Tic 104.25 24.12 28 6690 2958 79734712
Sinus bradycardia 76.68 24.12 39 6679 25208 79712462
Educational problem 76.01 24.12 15 6703 399 79737271
Suicidal ideation 71.81 24.12 56 6662 76284 79661386
Anger 62.48 24.12 30 6688 17132 79720538
Distributive shock 56.67 24.12 17 6701 2670 79735000
Hypotension 56.14 24.12 118 6600 440199 79297471
Intentional self-injury 54.54 24.12 34 6684 32385 79705285
Brugada syndrome 49.85 24.12 13 6705 1225 79736445
Product administered to patient of inappropriate age 48.19 24.12 18 6700 5535 79732135
Dystonia 47.93 24.12 27 6691 21372 79716298
Overdose 46.72 24.12 67 6651 184139 79553531
Autism spectrum disorder 45.92 24.12 12 6706 1140 79736530
Disturbance in attention 42.90 24.12 35 6683 50766 79686904
Attention deficit hyperactivity disorder 41.12 24.12 14 6704 3295 79734375
Priapism 40.55 24.12 15 6703 4490 79733180
Drug ineffective 39.32 24.12 187 6531 1080726 78656944
Mood swings 38.96 24.12 23 6695 19857 79717813
Sedation 38.14 24.12 33 6685 51862 79685808
Bradypnoea 36.25 24.12 15 6703 6037 79731633
Sinus arrest 36.09 24.12 13 6705 3609 79734061
Emotional disorder 34.53 24.12 19 6699 14368 79723302
Defiant behaviour 33.12 24.12 5 6713 24 79737646
Product quality issue 32.10 24.12 25 6693 33915 79703755
Disturbance in social behaviour 32.09 24.12 13 6705 4957 79732713
Suicide attempt 31.73 24.12 37 6681 82895 79654775
Affective disorder 31.67 24.12 15 6703 8304 79729366
Product use issue 31.14 24.12 60 6658 209762 79527908
Distractibility 30.85 24.12 8 6710 737 79736933
Cerebral disorder 30.73 24.12 13 6705 5525 79732145
Hallucination 30.73 24.12 37 6681 85708 79651962
Hyperammonaemia 30.40 24.12 16 6702 11077 79726593
Tachycardia 30.35 24.12 54 6664 177714 79559956
Insomnia 30.32 24.12 65 6653 245105 79492565
Drug dose titration not performed 30.19 24.12 8 6710 802 79736868
Homicidal ideation 29.25 24.12 11 6707 3446 79734224
Coma 29.06 24.12 39 6679 100610 79637060
Pain 28.29 24.12 12 6706 703790 79033880
Lethargy 27.38 24.12 34 6684 81258 79656412
Atrioventricular dissociation 25.99 24.12 6 6712 340 79737330
Accidental overdose 24.78 24.12 23 6695 39558 79698112

FDA Adverse Event Reporting System (Pediatric)

None

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
CHEBI has role CHEBI:176497 geroprotectors
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 | Suggest Off label Use Form| |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




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

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 2B GPCR Ki 5.88 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 6.12 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR AGONIST EC50 5.93 WOMBAT-PK
5-hydroxytryptamine receptor 2A GPCR Ki 6.07 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 6.26 DRUG MATRIX
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
DB01018 DRUGBANK_ID
CHEMBL1200494 ChEMBL_ID
D016316 MESH_DESCRIPTOR_UI
3519 PUBCHEM_CID
522 IUPHAR_LIGAND_ID
3999 INN_ID
30OMY4G3MK UNII
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 0228-2850 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 0228-2851 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 0228-2853 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 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 HUMAN PRESCRIPTION DRUG LABEL 1 0904-7140 TABLET 1 mg ORAL ANDA 24 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 0904-7140 TABLET 1 mg ORAL ANDA 24 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 16714-190 TABLET, EXTENDED RELEASE 1 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 16714-190 TABLET, EXTENDED RELEASE 1 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 16714-191 TABLET, EXTENDED RELEASE 2 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 16714-191 TABLET, EXTENDED RELEASE 2 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 16714-192 TABLET, EXTENDED RELEASE 3 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 16714-192 TABLET, EXTENDED RELEASE 3 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 16714-193 TABLET, EXTENDED RELEASE 4 mg ORAL ANDA 28 sections
Guanfacine HUMAN PRESCRIPTION DRUG LABEL 1 16714-193 TABLET, EXTENDED RELEASE 4 mg ORAL ANDA 28 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 Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 24979-198 TABLET 1 mg ORAL ANDA 13 sections
Guanfacine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 24979-199 TABLET 2 mg ORAL ANDA 13 sections
Guanfacine Extended-Release HUMAN PRESCRIPTION DRUG LABEL 1 24979-533 TABLET, EXTENDED RELEASE 1 mg ORAL ANDA 28 sections