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

Stem definitionDrug idCAS RN
antihypertensives, hydrazinephthalazine derivatives 1384 86-54-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • hydralazine
  • hydralazine hydrochloride
  • hydralazine HCl
A direct-acting vasodilator that is used as an antihypertensive agent.
  • Molecular weight: 160.18
  • Formula: C8H8N4
  • CLOGP: 1.17
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 63.83
  • ALOGS: -1.79
  • ROTB: 1

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 44.20 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 8 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 20.79 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 23 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.50 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 85 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.12 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 15, 1953 FDA

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
Anti-neutrophil cytoplasmic antibody positive vasculitis 1020.33 54.90 129 813 211 2356932
Exposure during pregnancy 374.33 54.90 109 833 25110 2332033
Glomerulonephritis rapidly progressive 325.36 54.90 44 898 141 2357002
Pulmonary renal syndrome 317.45 54.90 38 904 23 2357120
Vasculitis 286.50 54.90 56 886 2262 2354881
Glomerulonephritis 278.17 54.90 43 899 413 2356730
Maternal exposure during pregnancy 258.47 54.90 73 869 14790 2342353
Gastrointestinal tract mucosal pigmentation 201.94 54.90 24 918 12 2357131
Completed suicide 187.93 54.90 62 880 20972 2336171
Lupus-like syndrome 167.16 54.90 35 907 1979 2355164
Premature delivery 129.95 54.90 31 911 3169 2353974
Premature baby 129.91 54.90 31 911 3173 2353970
Hypertension 127.87 54.90 50 892 27311 2329832
Pre-eclampsia 123.92 54.90 26 916 1478 2355665
Drug hypersensitivity 123.85 54.90 57 885 46586 2310557
Renal vasculitis 122.82 54.90 16 926 34 2357109
Glomerulonephritis proliferative 122.31 54.90 17 925 69 2357074
Pulmonary alveolar haemorrhage 117.03 54.90 22 920 707 2356436
Acute kidney injury 105.77 54.90 44 898 28078 2329065
Premature labour 104.39 54.90 24 918 2082 2355061
Hypotension 102.98 54.90 45 897 32391 2324752
Systemic lupus erythematosus 101.99 54.90 27 915 4194 2352949
Low birth weight baby 95.83 54.90 19 923 810 2356333
Caesarean section 79.32 54.90 22 920 4059 2353084
Dyspnoea 77.71 54.90 50 892 78683 2278460
Toxicity to various agents 71.18 54.90 35 907 32719 2324424
Cutaneous vasculitis 65.51 54.90 12 930 332 2356811
Drug-induced liver injury 63.04 54.90 18 924 3681 2353462
Acute febrile neutrophilic dermatosis 62.13 54.90 12 930 444 2356699
Foetal exposure during pregnancy 60.99 54.90 19 923 5233 2351910
Lupus nephritis 59.81 54.90 11 931 311 2356832
Foetal death 59.61 54.90 15 927 1897 2355246
Blood pressure increased 58.38 54.90 25 917 16961 2340182
Small for dates baby 57.58 54.90 12 930 655 2356488
Antineutrophil cytoplasmic antibody positive 56.23 54.90 9 933 108 2357035

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
Anti-neutrophil cytoplasmic antibody positive vasculitis 634.37 53.83 78 535 74 1746094
Lupus-like syndrome 237.80 53.83 40 573 633 1745535
Completed suicide 191.60 53.83 60 553 16252 1729916
Glomerulonephritis rapidly progressive 191.41 53.83 27 586 116 1746052
Acute kidney injury 186.08 53.83 71 542 34873 1711295
Hypotension 156.46 53.83 60 553 29594 1716574
Vasculitis 149.86 53.83 31 582 1544 1744624
Pulmonary renal syndrome 138.50 53.83 17 596 14 1746154
Pulmonary oedema 110.23 53.83 32 581 6554 1739614
Foetal exposure during pregnancy 102.42 53.83 30 583 6329 1739839
Low birth weight baby 93.26 53.83 19 594 868 1745300
Glomerulonephritis 91.56 53.83 17 596 474 1745694
Premature baby 89.89 53.83 23 590 2919 1743249
Gastrointestinal tract mucosal pigmentation 88.54 53.83 11 602 11 1746157
Cardiomegaly 84.97 53.83 21 592 2313 1743855
Pericardial effusion 81.90 53.83 22 591 3368 1742800
Overdose 81.02 53.83 32 581 16669 1729499
Troponin I increased 78.60 53.83 14 599 307 1745861
Apgar score low 75.57 53.83 13 600 231 1745937
Proteinuria 71.24 53.83 19 594 2825 1743343
Blood lactic acid increased 69.84 53.83 15 598 884 1745284
Toxicity to various agents 60.95 53.83 31 582 29110 1717058
Renal vasculitis 54.80 53.83 8 605 45 1746123

Pharmacologic Action:

SourceCodeDescription
ATC C02DB02 CARDIOVASCULAR SYSTEM
ANTIHYPERTENSIVES
ARTERIOLAR SMOOTH MUSCLE, AGENTS ACTING ON
Hydrazinophthalazine derivatives
ATC C02LG02 CARDIOVASCULAR SYSTEM
ANTIHYPERTENSIVES
ANTIHYPERTENSIVES AND DIURETICS IN COMBINATION
Hydrazinophthalazine derivatives and diuretics
CHEBI has role CHEBI:35674 antihypertensive agent
CHEBI has role CHEBI:35620 vasodilator agent
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
FDA PE N0000175379 Arteriolar Vasodilation
FDA EPC N0000175564 Arteriolar Vasodilator
MeSH PA D014665 Vasodilator Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Chronic heart failure indication 48447003
Anuria contraindication 2472002 DOID:2983
Suicidal thoughts contraindication 6471006
Peptic ulcer contraindication 13200003 DOID:750
Hypercholesterolemia contraindication 13644009
Chronic disease of respiratory system contraindication 17097001
Secondary angle-closure glaucoma contraindication 21571006
Myocardial infarction contraindication 22298006 DOID:5844
Electroconvulsive therapy contraindication 23835007
Hypovolemia contraindication 28560003
Dehydration contraindication 34095006
Hyperthyroidism contraindication 34486009 DOID:7998
Depressive disorder contraindication 35489007
Hyperuricemia contraindication 35885006 DOID:1920
Hypokalemia contraindication 43339004
Conduction disorder of the heart contraindication 44808001
Low blood pressure contraindication 45007003
Systemic lupus erythematosus contraindication 55464009 DOID:9074
Sympathectomy contraindication 57071006
Ulcerative colitis contraindication 64766004 DOID:8577
Hypercalcemia contraindication 66931009 DOID:12678
Hyperparathyroidism contraindication 66999008 DOID:13543
Benign intracranial hypertension contraindication 68267002 DOID:11459
Hypochloremic alkalosis contraindication 70134007
Hepatic coma contraindication 72836002 DOID:12550
Diabetes mellitus contraindication 73211009 DOID:9351
Injury of head contraindication 82271004
Epilepsy contraindication 84757009 DOID:1826
Hyponatremia contraindication 89627008
Gout contraindication 90560007 DOID:13189
Kidney disease contraindication 90708001 DOID:557
Increased intestinal motility contraindication 102624003
Hypomagnesemia contraindication 190855004
Acute pancreatitis contraindication 197456007 DOID:2913
Cerebrovascular accident contraindication 230690007
Hypertrophic cardiomyopathy contraindication 233873004 DOID:11984
Lupus erythematosus and erythema multiforme-like syndrome contraindication 238926009
Calculus in biliary tract contraindication 266474003
Anemia contraindication 271737000 DOID:2355
Cerebral hemorrhage contraindication 274100004
Neonatal hyperbilirubinemia contraindication 281610001
Disorder of coronary artery contraindication 414024009
Myocardial infarction in recovery phase contraindication 418044006
Slow acetylator due to N-acetyltransferase enzyme variant contraindication 425079005
Azotemia contraindication 445009001
Malabsorption States contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.81 Basic
pKa2 3.26 Basic
pKa3 2.62 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
37.5MG BIDIL ARBOR PHARMS LLC N020727 June 23, 2005 RX TABLET ORAL 6465463 Sept. 8, 2020 METHOD OF TREATMENT OF HEART FAILURE
37.5MG BIDIL ARBOR PHARMS LLC N020727 June 23, 2005 RX TABLET ORAL 6784177 Sept. 8, 2020 METHOD OF TREATMENT OF HEART FAILURE

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Ryanodine receptor 2 Ion channel BLOCKER SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
DNA (cytosine-5)-methyltransferase 3B Enzyme WOMBAT-PK
DNA (cytosine-5)-methyltransferase 3A Enzyme WOMBAT-PK
DNA (cytosine-5)-methyltransferase 1 Enzyme WOMBAT-PK
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel WOMBAT-PK
Aldehyde oxidase Enzyme WOMBAT-PK
Ryanodine receptor 2 Ion channel IC50 7.15 SCIENTIFIC LITERATURE
Cholinesterase Enzyme Ki 5.72 CHEMBL
Acetylcholinesterase Enzyme Ki 5.15 CHEMBL
Arachidonate 15-lipoxygenase Enzyme IC50 5.44 DRUG MATRIX

External reference:

IDSource
D006830 MESH_DESCRIPTOR_UI
4019778 VUID
N0000147869 NUI
C0020223 UMLSCUI
D01302 KEGG_DRUG
26NAK24LS8 UNII
1 INN_ID
22696000 SNOMEDCT_US
5470 RXNORM
387125005 SNOMEDCT_US
d00132 MMSL
4019778 VANDF
004489 NDDF
3637 PUBCHEM_CID
CHEBI:5775 CHEBI
CHEMBL276832 ChEMBL_ID
CHEMBL542541 ChEMBL_ID
304-20-1 SECONDARY_CAS_RN
HLZ PDB_CHEM_ID
DB01275 DRUGBANK_ID
7326 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0517-0901 INJECTION, SOLUTION 20 mg INTRAMUSCULAR ANDA 12 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0615-0516 TABLET 10 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0615-0531 TABLET 25 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0615-0532 TABLET 50 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0615-5649 TABLET 100 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0615-7973 TABLET 100 mg ORAL ANDA 9 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6440 TABLET, FILM COATED 10 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6441 TABLET, FILM COATED 25 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6442 TABLET, FILM COATED 50 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6443 TABLET, FILM COATED 100 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17478-834 INJECTION 20 mg INTRAMUSCULAR ANDA 12 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17478-934 INJECTION 20 mg INTRAVENOUS ANDA 12 sections
HYDRALAZINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 21695-679 TABLET 10 mg ORAL ANDA 12 sections
HYDRALAZINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 21695-680 TABLET 25 mg ORAL ANDA 12 sections
HYDRALAZINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 21695-694 TABLET 50 mg ORAL ANDA 12 sections
HYDRALAZINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 21695-695 TABLET 100 mg ORAL ANDA 12 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 23155-001 TABLET, FILM COATED 10 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 23155-002 TABLET, FILM COATED 25 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 23155-003 TABLET, FILM COATED 50 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 23155-004 TABLET, FILM COATED 100 mg ORAL ANDA 11 sections
BiDil HUMAN PRESCRIPTION DRUG LABEL 2 24338-010 TABLET, FILM COATED 37.50 mg ORAL NDA 17 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 31722-519 TABLET 10 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 31722-520 TABLET 25 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 31722-521 TABLET 50 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 31722-522 TABLET 100 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 35356-943 TABLET 50 mg ORAL ANDA 12 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 39822-0500 INJECTION, SOLUTION 20 mg INTRAMUSCULAR ANDA 12 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43063-392 TABLET, FILM COATED 50 mg ORAL ANDA 11 sections
Hydralazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43353-124 TABLET 100 mg ORAL ANDA 12 sections
HydrALAZINE Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43353-205 TABLET 100 mg ORAL ANDA 12 sections