digitoxin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
881 71-63-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • digitoxin
  • digitoxoside
  • cardidigin
  • cardigin
  • carditoxin
  • coramedan
  • cristapurat
  • crystodigin
  • digicor
  • digipural
  • digisidin
  • digitophyllin
  • digitoxigenin tridigitoxoside
  • myodigin
  • purpurid
  • tradigal
  • unidigin
A cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting. (From Martindale, The Extra Pharmacopoeia, 30th ed, p665)
  • Molecular weight: 764.95
  • Formula: C41H64O13
  • CLOGP: 2.85
  • LIPINSKI: 2
  • HAC: 13
  • HDO: 5
  • TPSA: 182.83
  • ALOGS: -4.42
  • ROTB: 7
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 mg O
0.10 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.01 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 30 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.00 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 95 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.44 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.04 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.07 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 180 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.809 Moderate 0.68
caco2-efflux Caco-2 efflux ratio (BA/AB) 12.706 Moderate 0.68
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 19.498 10^-6 cm/s Moderate 0.68
dh-clint Dog hepatocyte intrinsic clearance 2.355 uL/min/10^6 cells Moderate 0.68
dppb Dog plasma protein binding (% unbound) 32.720 % Moderate 0.68
fcs-ppb Fetal calf serum protein binding (% unbound) 33.540 % Moderate 0.68
herg hERG pIC50 4.429 pIC50 Moderate 0.68
hh-clint Human hepatocyte intrinsic clearance 1.795 uL/min/10^6 cells Moderate 0.68
hlm-clint Human liver microsomal intrinsic clearance 6.808 uL/min/mg protein Moderate 0.68
hppb Human plasma protein binding (% unbound) 34.420 % Moderate 0.68
kinase-safety-class ACVR2B,CDK5,EIF2AK3,GRK2,ITK,PDK1,PDK2,PDK4,PRKDC 9
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 45.186 High 0.80
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 19.011 Moderate 0.68
mh-clint Mouse hepatocyte intrinsic clearance 7.870 Moderate 0.68
mppb Mouse plasma protein binding (% unbound) 20.860 Moderate 0.68
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 42.560 Moderate 0.68
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 0.80
pppb Pig plasma protein binding (% unbound) 36.420 % Moderate 0.68
rat-kpuu-brain Rat brain Kpuu 0.034 % High 0.80
rh-clint Rat hepatocyte intrinsic clearance 3.837 uL/min/10^6 cells Moderate 0.68
rh-fuinc Rat hepatocyte fraction unbound in incubation 67.330 % Moderate 0.68
rppb Rat plasma protein binding (% unbound) 32.570 % Moderate 0.68
solubility-dd Solubility at pH 7.4 in DMSO 772.681 uM Moderate 0.68

Approvals:

DateAgencyCompanyOrphan
None FDA LILLY

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
Atrial fibrillation 250.32 32.46 123 4154 133488 90490682
General physical health deterioration 190.98 32.46 147 4130 354968 90269202
Product prescribing error 173.88 32.46 62 4215 30083 90594087
Arrhythmia 170.84 32.46 67 4210 42265 90581905
Product monitoring error 164.32 32.46 39 4238 4505 90619665
Bradycardia 150.20 32.46 75 4202 83772 90540398
Fall 140.68 32.46 141 4136 481669 90142501
Anaemia 115.37 32.46 110 4167 352692 90271478
Tachycardia 106.26 32.46 75 4202 157598 90466572
Therapeutic drug monitoring analysis not performed 95.41 32.46 20 4257 1309 90622861
Syncope 89.10 32.46 63 4214 132600 90491570
Haematochezia 86.10 32.46 49 4228 70864 90553306
Systemic infection 74.50 32.46 21 4256 4754 90619416
Dyspnoea 69.03 32.46 137 4140 880818 89743352
Cardiac failure 66.62 32.46 49 4228 109447 90514723
Toxic epidermal necrolysis 63.80 32.46 31 4246 32497 90591673
Stevens-Johnson syndrome 57.63 32.46 28 4249 29348 90594822
Dizziness 56.40 32.46 100 4177 589184 90034986
Cerebrospinal fluid retention 52.08 32.46 8 4269 85 90624085
Fracture 49.27 32.46 23 4254 22053 90602117
Drug ineffective 47.91 32.46 5 4272 1384293 89239877
Dehydration 45.86 32.46 51 4226 194396 90429774
Cerebral ventricular rupture 45.12 32.46 8 4269 214 90623956
Labelled drug-drug interaction medication error 44.77 32.46 19 4258 14563 90609607
Therapeutic drug monitoring analysis incorrectly performed 41.69 32.46 8 4269 333 90623837
Spontaneous haemorrhage 41.10 32.46 9 4268 724 90623446
Gastric pH increased 40.70 32.46 6 4271 47 90624123
Cerebellar infarction 40.13 32.46 11 4266 2247 90621923
Diverticulum intestinal haemorrhagic 38.00 32.46 10 4267 1751 90622419
Pulmonary vein occlusion 37.14 32.46 6 4271 90 90624080
Atrial flutter 36.32 32.46 15 4262 10743 90613427
Restlessness 36.25 32.46 22 4255 35698 90588472
Reflexes abnormal 35.21 32.46 8 4269 761 90623409
Bradyarrhythmia 34.68 32.46 10 4267 2451 90621719
Pallor 34.56 32.46 21 4256 34144 90590026

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
General physical health deterioration 221.75 32.86 166 4948 151080 42465141
Product monitoring error 103.93 32.86 33 5081 4390 42611831
Product prescribing error 103.12 32.86 54 5060 26058 42590163
Renal cyst haemorrhage 100.94 32.86 22 5092 668 42615553
Rectal prolapse 99.45 32.86 21 5093 547 42615674
Haematochezia 89.33 32.86 66 5048 58370 42557851
Oedema peripheral 85.70 32.86 93 5021 135983 42480238
Atrial fibrillation 78.61 32.86 90 5024 139503 42476718
Abdominal wall haemorrhage 78.48 32.86 17 5097 501 42615720
Dyspnoea 75.25 32.86 164 4950 442457 42173764
Vena cava injury 73.50 32.86 15 5099 329 42615892
SARS-CoV-2 antibody test positive 71.09 32.86 15 5099 389 42615832
Carotid arteriosclerosis 70.00 32.86 21 5093 2311 42613910
Bradycardia 69.32 32.86 67 5047 85417 42530804
Vascular anastomotic haemorrhage 68.95 32.86 14 5100 299 42615922
Systemic infection 67.92 32.86 25 5089 5180 42611041
Delayed graft function 67.47 32.86 21 5093 2614 42613607
Spinal stenosis 62.88 32.86 25 5089 6381 42609840
Hyperparathyroidism secondary 61.45 32.86 18 5096 1824 42614397
Vascular compression 60.08 32.86 13 5101 381 42615840
Mean cell volume increased 59.27 32.86 21 5093 3902 42612319
Aortic dilatation 58.73 32.86 17 5097 1652 42614569
Diverticulum intestinal 57.41 32.86 22 5092 5091 42611130
Aortic arteriosclerosis 57.38 32.86 22 5092 5098 42611123
Intraductal papillary mucinous neoplasm 57.23 32.86 13 5101 478 42615743
Hepatosplenomegaly 55.74 32.86 21 5093 4639 42611582
Spinal osteoarthritis 55.54 32.86 25 5089 8661 42607560
Perineal cyst 54.12 32.86 11 5103 236 42615985
Actinic keratosis 53.60 32.86 21 5093 5155 42611066
Renal artery stenosis 53.23 32.86 17 5097 2300 42613921
Intervertebral disc space narrowing 50.89 32.86 14 5100 1131 42615090
Blood 25-hydroxycholecalciferol decreased 50.52 32.86 11 5103 332 42615889
Labelled drug-drug interaction medication error 49.72 32.86 28 5086 15554 42600667
Therapeutic drug monitoring analysis not performed 44.74 32.86 11 5103 571 42615650
Electrocardiogram abnormal 42.94 32.86 22 5092 10123 42606098
Left ventricular hypertrophy 41.75 32.86 21 5093 9298 42606923
Restless legs syndrome 41.13 32.86 21 5093 9593 42606628
Therapeutic drug monitoring analysis incorrectly performed 40.02 32.86 9 5105 316 42615905
Swelling of eyelid 38.36 32.86 13 5101 2115 42614106
Glycosylated haemoglobin increased 37.94 32.86 22 5092 12902 42603319
C-reactive protein increased 37.40 32.86 42 5072 63518 42552703
Squamous cell carcinoma of skin 35.61 32.86 21 5093 12705 42603516
Vitamin D decreased 35.38 32.86 15 5099 4500 42611721
Wound 34.66 32.86 23 5091 17094 42599127
Off label use 34.35 32.86 17 5097 638318 41977903
Tongue biting 33.54 32.86 10 5104 1077 42615144
Albumin urine present 32.90 32.86 8 5106 396 42615825

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
General physical health deterioration 385.57 31.63 298 8586 424997 110155418
Atrial fibrillation 294.59 31.63 199 8685 229443 110350972
Product prescribing error 275.91 31.63 116 8768 51215 110529200
Product monitoring error 260.86 31.63 72 8812 8855 110571560
Bradycardia 211.72 31.63 140 8744 155377 110425038
Haematochezia 174.33 31.63 111 8773 115413 110465002
Systemic infection 141.94 31.63 46 8838 9773 110570642
Dyspnoea 141.66 31.63 288 8596 1106584 109473831
Arrhythmia 141.47 31.63 81 8803 69494 110510921
Therapeutic drug monitoring analysis not performed 133.43 31.63 31 8853 1900 110578515
Anaemia 130.37 31.63 188 8696 546898 110033517
Renal cyst haemorrhage 107.57 31.63 22 8862 739 110579676
Fall 93.88 31.63 171 8713 603311 109977104
Labelled drug-drug interaction medication error 93.20 31.63 46 8838 29256 110551159
Syncope 87.48 31.63 94 8790 202442 110377973
Oedema peripheral 87.06 31.63 119 8765 328541 110251874
Toxic epidermal necrolysis 86.69 31.63 55 8829 56672 110523743
Therapeutic drug monitoring analysis incorrectly performed 79.88 31.63 17 8867 695 110579720
Vena cava injury 79.15 31.63 15 8869 337 110580078
Abdominal wall haemorrhage 78.93 31.63 17 8867 736 110579679
SARS-CoV-2 antibody test positive 76.68 31.63 15 8869 400 110580015
Rectal prolapse 76.35 31.63 21 8863 2542 110577873
Vascular anastomotic haemorrhage 74.55 31.63 14 8870 299 110580116
Carotid arteriosclerosis 72.69 31.63 21 8863 3036 110577379
Cardiac failure 68.84 31.63 80 8804 187546 110392869
Delayed graft function 65.83 31.63 21 8863 4236 110576179
Spontaneous haemorrhage 65.79 31.63 16 8868 1192 110579223
Aortic dilatation 65.05 31.63 18 8866 2228 110578187
Stevens-Johnson syndrome 63.12 31.63 42 8842 46859 110533556
Drug ineffective 61.30 31.63 23 8861 1520517 109059898
Restlessness 60.74 31.63 44 8840 56215 110524200
Tachycardia 59.84 31.63 82 8802 226563 110353852
Perineal cyst 58.66 31.63 11 8873 233 110580182
Hyperparathyroidism secondary 58.19 31.63 18 8866 3286 110577129
Vascular compression 56.41 31.63 13 8871 768 110579647
Dizziness 56.15 31.63 152 8732 698041 109882374
Hepatosplenomegaly 55.85 31.63 21 8863 6898 110573517
Actinic keratosis 55.57 31.63 21 8863 6992 110573423
Electrocardiogram abnormal 55.44 31.63 28 8856 18681 110561734
Intraductal papillary mucinous neoplasm 55.18 31.63 13 8871 846 110579569
Pallor 53.87 31.63 41 8843 56426 110523989
Aortic arteriosclerosis 53.00 31.63 23 8861 10915 110569500
Mean cell volume increased 52.06 31.63 21 8863 8309 110572106
Renal artery stenosis 51.99 31.63 17 8867 3709 110576706
Blood 25-hydroxycholecalciferol decreased 51.33 31.63 11 8873 465 110579950
Intervertebral disc space narrowing 49.46 31.63 14 8870 1882 110578533
Diverticulum intestinal 48.30 31.63 22 8862 11697 110568718
Dehydration 48.17 31.63 83 8801 279428 110300987
Off label use 47.88 31.63 31 8853 1500154 109080261
Cerebrospinal fluid retention 46.48 31.63 8 8876 102 110580313
Spinal stenosis 46.39 31.63 25 8859 19031 110561384
Spinal osteoarthritis 45.04 31.63 25 8859 20158 110560257
Left ventricular hypertrophy 42.72 31.63 21 8863 13223 110567192
Activated partial thromboplastin time prolonged 42.65 31.63 25 8859 22343 110558072
Renal impairment 42.10 31.63 63 8821 188382 110392033
Benign prostatic hyperplasia 41.83 31.63 23 8861 18211 110562204
Squamous cell carcinoma of skin 37.55 31.63 21 8863 17182 110563233
Personality change 37.15 31.63 18 8866 10984 110569431
Wound 36.99 31.63 67 8817 234370 110346045
Gastric pH increased 35.76 31.63 6 8878 65 110580350
Fracture 35.29 31.63 23 8861 24765 110555650
Cerebral ventricular rupture 34.81 31.63 8 8876 467 110579948
Hyperkalaemia 34.10 31.63 48 8836 135748 110444667
Thoracic haemorrhage 33.06 31.63 7 8877 279 110580136
Restless legs syndrome 33.00 31.63 22 8862 24604 110555811
Malaise 32.80 31.63 7 8877 671812 109908603
Ventricular arrhythmia 32.55 31.63 16 8868 10071 110570344
Pulmonary vein occlusion 31.86 31.63 6 8878 130 110580285

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C01AA04 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
CARDIAC GLYCOSIDES
Digitalis glycosides
MeSH PA D000889 Anti-Arrhythmia Agents
MeSH PA D002316 Cardiotonic Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D020011 Protective Agents
CHEBI has role CHEBI:63510 EC 3.6.3.9 (<em>Na</em><small><sup>+</small></sup>/<em>K</em><small><sup>+</small></sup>-transporting ATPase) inhibitor

Related Drugs by ATC class:

C01AA Digitalis glycosides 7 drugs
acetyldigitoxinacetyldigoxindeslanosidedigoxingitoformatelanatoside Cmetildigoxin

Drug Use | Suggest Off label Use Form| |View source of the data|

None




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

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
Sodium/potassium-transporting ATPase subunit alpha-1 Transporter INHIBITOR WOMBAT-PK CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.86 WOMBAT-PK
Signal transducer and activator of transcription 3 Transcription factor IC50 6.15 CHEMBL
Sodium/potassium-transporting ATPase Transporter IC50 8.10 CHEMBL
Sodium/potassium-transporting ATPase subunit alpha-2 Ion channel IC50 6.65 DRUG MATRIX
Sodium/potassium-transporting ATPase subunit alpha-1 Transporter IC50 8.10 CHEMBL

External reference:

IDSource
4017429 VUID
N0000145817 NUI
D00297 KEGG_DRUG
216288 RXNORM
4017429 VANDF
C0012258 UMLSCUI
CHEBI:28544 CHEBI
F9R PDB_CHEM_ID
CHEMBL254219 ChEMBL_ID
D004074 MESH_DESCRIPTOR_UI
DB01396 DRUGBANK_ID
6782 IUPHAR_LIGAND_ID
1547 INN_ID
E90NZP2L9U UNII
441207 PUBCHEM_CID
195 MMSL
4596 MMSL
d00209 MMSL
000592 NDDF
373534001 SNOMEDCT_US
81728006 SNOMEDCT_US

Pharmaceutical products:

None