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

Stem definitionDrug idCAS RN
882 20830-75-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • digoxin
  • cardiogoxin
  • digoxine
A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)
  • Molecular weight: 780.95
  • Formula: C41H64O14
  • CLOGP: 1.42
  • LIPINSKI: 3
  • HAC: 14
  • HDO: 6
  • TPSA: 203.06
  • ALOGS: -3.79
  • ROTB: 7

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
0.25 mg O
0.25 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.99 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 60 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.00 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 70 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 4.10 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.70 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.70 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 38 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Oct. 24, 1975 FDA EUROHLTH INTL SARL

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
Toxicity to various agents 2429.87 58.99 603 1777 32151 2323554
Bradycardia 1556.85 58.99 340 2040 9641 2346064
Cardioactive drug level increased 1348.09 58.99 184 2196 149 2355556
Nausea 644.95 58.99 308 2072 111881 2243824
Acute kidney injury 631.35 58.99 208 2172 27914 2327791
Atrial fibrillation 528.44 58.99 154 2226 13614 2342091
Vomiting 512.50 58.99 230 2150 71372 2284333
Hyperkalaemia 467.09 58.99 117 2263 5776 2349929
Product complaint 445.22 58.99 107 2273 4431 2351274
Drug interaction 444.69 58.99 162 2218 29001 2326704
Dizziness 442.77 58.99 196 2184 58469 2297236
Asthenia 403.06 58.99 172 2208 46754 2308951
Hypotension 398.91 58.99 154 2226 32282 2323423
Decreased appetite 301.34 58.99 122 2258 28769 2326936
Overdose 292.76 58.99 108 2272 19799 2335906
Drug level increased 264.03 58.99 64 2316 2723 2352982
Ventricular tachycardia 259.11 58.99 64 2316 2947 2352758
International normalised ratio increased 253.78 58.99 76 2304 7260 2348445
Heart rate decreased 251.30 58.99 65 2315 3611 2352094
Atrioventricular block 240.80 58.99 51 2329 1166 2354539
Renal failure 239.70 58.99 90 2290 17259 2338446
Atrioventricular block complete 238.77 58.99 52 2328 1362 2354343
Dehydration 238.42 58.99 96 2284 22199 2333506
Confusional state 226.88 58.99 95 2285 24249 2331456
Diarrhoea 220.97 58.99 139 2241 83425 2272280
Cardiac failure 216.43 58.99 76 2304 12018 2343687
Dyspnoea 198.03 58.99 127 2253 78606 2277099
Cardiac arrest 193.56 58.99 74 2306 14856 2340849
Torsade de pointes 189.39 58.99 47 2333 2199 2353506
Cardioactive drug level above therapeutic 187.33 58.99 25 2355 12 2355693
Electrocardiogram QT prolonged 186.50 58.99 61 2319 7753 2347952
Fatigue 179.67 58.99 123 2257 84750 2270955
Atrioventricular block second degree 178.41 58.99 36 2344 641 2355064
Sinus bradycardia 177.00 58.99 44 2336 2072 2353633
Maternal exposure during pregnancy 172.50 58.99 68 2312 14795 2340910
Blood creatinine increased 168.65 58.99 61 2319 10472 2345233
Syncope 164.14 58.99 68 2312 16807 2338898
Nodal rhythm 160.31 58.99 30 2350 352 2355353
Visual impairment 154.87 58.99 59 2321 11696 2344009
Blood potassium increased 145.88 58.99 38 2342 2158 2353547
Metabolic acidosis 143.73 58.99 47 2333 5951 2349754
Arrhythmia 143.50 58.99 47 2333 5981 2349724
Bradyarrhythmia 142.43 58.99 27 2353 341 2355364
Atrioventricular block first degree 137.97 58.99 31 2349 936 2354769
Vision blurred 135.46 58.99 57 2323 14611 2341094
Condition aggravated 133.85 58.99 72 2308 31907 2323798
Multiple organ dysfunction syndrome 132.58 58.99 47 2333 7594 2348111
Fall 125.33 58.99 79 2301 47020 2308685
Hypokalaemia 117.37 58.99 47 2333 10607 2345098
Ventricular extrasystoles 116.11 58.99 31 2349 1935 2353770
Lethargy 115.54 58.99 44 2336 8686 2347019
Toxic epidermal necrolysis 114.68 58.99 34 2346 3110 2352595
Electrolyte imbalance 110.32 58.99 30 2350 2007 2353698
Ventricular fibrillation 103.44 58.99 29 2351 2172 2353533
Cardiogenic shock 99.89 58.99 29 2351 2462 2353243
Adverse drug reaction 99.79 58.99 39 2341 8244 2347461
Completed suicide 98.16 58.99 51 2329 20983 2334722
Sinus node dysfunction 97.62 58.99 22 2358 672 2355033
Malaise 97.24 58.99 72 2308 55513 2300192
Hyperthyroidism 95.68 58.99 27 2353 2070 2353635
Nodal arrhythmia 94.51 58.99 18 2362 233 2355472
Hyponatraemia 91.24 58.99 42 2338 13283 2342422
Bundle branch block right 87.97 58.99 21 2359 829 2354876
Abdominal pain 87.11 58.99 56 2324 34318 2321387
Respiratory disorder 86.34 58.99 29 2351 3975 2351730
Foetal exposure during pregnancy 86.10 58.99 31 2349 5221 2350484
Loss of consciousness 86.09 58.99 45 2335 18722 2336983
Blood pressure decreased 85.51 58.99 36 2344 9200 2346505
Cholecystitis 85.05 58.99 25 2355 2215 2353490
Medication error 85.04 58.99 32 2348 6099 2349606
Weight decreased 83.90 58.99 51 2329 28320 2327385
Heart rate increased 82.31 58.99 37 2343 11068 2344637
Premature delivery 80.33 58.99 26 2354 3174 2352531
Palpitations 79.89 58.99 41 2339 16415 2339290
Presyncope 79.85 58.99 27 2353 3776 2351929
Somnolence 79.30 58.99 46 2334 23439 2332266
Renal impairment 79.19 58.99 35 2345 10057 2345648
Exposure during pregnancy 78.86 58.99 47 2333 25172 2330533
Electrocardiogram abnormal 78.36 58.99 21 2359 1327 2354378
Electrocardiogram QRS complex prolonged 77.65 58.99 20 2360 1082 2354623
Tachyarrhythmia 77.60 58.99 18 2362 626 2355079
Mental status changes 76.92 58.99 29 2351 5553 2350152
Dermatitis exfoliative 75.29 58.99 20 2360 1221 2354484
Electrocardiogram ST segment depression 74.03 58.99 17 2363 565 2355140
Atrial flutter 70.93 58.99 19 2361 1198 2354507
Atrial tachycardia 70.50 58.99 15 2365 348 2355357
Supraventricular extrasystoles 70.06 58.99 17 2363 719 2354986
Blood urea increased 69.45 58.99 24 2356 3581 2352124
Subarachnoid haemorrhage 69.15 58.99 21 2359 2079 2353626
Drug ineffective 68.47 58.99 77 2303 101547 2254158
General physical health deterioration 67.95 58.99 35 2345 14104 2341601
Delirium 67.87 58.99 26 2354 5197 2350508
Xanthopsia 67.69 58.99 11 2369 51 2355654
Orthopnoea 66.95 58.99 16 2364 634 2355071
Cardiac failure congestive 66.44 58.99 36 2344 16065 2339640
Death 65.84 58.99 68 2312 81400 2274305
Bundle branch block left 65.16 58.99 17 2363 967 2354738
Left atrial dilatation 63.27 58.99 13 2367 253 2355452
Supraventricular tachycardia 61.51 58.99 19 2361 1990 2353715
Incorrect dose administered 61.48 58.99 29 2351 9666 2346039
Left ventricular dysfunction 61.27 58.99 17 2363 1223 2354482
Hallucination 59.87 58.99 27 2353 8121 2347584
Disorientation 59.49 58.99 25 2355 6347 2349358

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
Toxicity to various agents 1877.52 51.43 522 1630 28619 1716010
Bradycardia 1822.13 51.43 418 1734 10116 1734513
Cardioactive drug level increased 957.54 51.43 139 2013 120 1744509
Dizziness 566.11 51.43 224 1928 34137 1710492
Atrial fibrillation 518.15 51.43 170 1982 14941 1729688
Acute kidney injury 485.94 51.43 202 1950 34742 1709887
Hypotension 447.54 51.43 182 1970 29472 1715157
Hyperkalaemia 442.35 51.43 132 2020 8415 1736214
Nausea 421.00 51.43 205 1947 50991 1693638
Product complaint 392.23 51.43 93 2059 2397 1742232
Ventricular tachycardia 343.63 51.43 91 2061 3707 1740922
Vomiting 321.14 51.43 156 1996 38159 1706470
Drug interaction 277.05 51.43 128 2024 27830 1716799
Dyspnoea 235.73 51.43 141 2011 51918 1692711
Venous pressure jugular increased 216.85 51.43 34 2118 69 1744560
Fatigue 215.41 51.43 132 2020 50649 1693980
Cardiac murmur 209.61 51.43 49 2103 1173 1743456
Renal failure 205.04 51.43 94 2058 19923 1724706
Cardiac failure 194.03 51.43 79 2073 12523 1732106
Cardiac arrest 192.39 51.43 84 2068 15846 1728783
Asthenia 191.14 51.43 107 2045 34563 1710066
Atrioventricular block complete 185.38 51.43 46 2106 1425 1743204
Overdose 185.35 51.43 83 2069 16618 1728011
Decreased appetite 183.31 51.43 92 2060 23779 1720850
Confusional state 175.13 51.43 86 2066 21192 1723437
Syncope 168.64 51.43 74 2078 14095 1730534
Completed suicide 164.90 51.43 76 2076 16236 1728393
Atrioventricular block 158.39 51.43 40 2112 1331 1743298
Heart rate decreased 155.89 51.43 46 2106 2763 1741866
Drug level increased 143.32 51.43 43 2109 2734 1741895
Renal impairment 132.55 51.43 60 2092 12254 1732375
Cardioactive drug level above therapeutic 130.27 51.43 18 2134 5 1744624
Nodal rhythm 127.65 51.43 26 2126 316 1744313
Malaise 124.93 51.43 77 2075 29488 1715141
Left ventricular dysfunction 123.50 51.43 32 2120 1179 1743450
Oedema peripheral 122.16 51.43 61 2091 15489 1729140
Ventricular extrasystoles 117.48 51.43 34 2118 1902 1742727
Arrhythmia 114.31 51.43 44 2108 5972 1738657
Dehydration 112.01 51.43 60 2092 17598 1727031
Foetal exposure during pregnancy 108.43 51.43 43 2109 6316 1738313
Condition aggravated 107.20 51.43 62 2090 21088 1723541
Blood creatinine increased 104.46 51.43 53 2099 13893 1730736
International normalised ratio increased 103.89 51.43 45 2107 8254 1736375
Diarrhoea 103.88 51.43 87 2065 53765 1690864
General physical health deterioration 98.65 51.43 50 2102 13068 1731561
Vision blurred 96.76 51.43 43 2109 8380 1736249
Cardiac failure congestive 94.28 51.43 51 2101 15219 1729410
Atrial flutter 91.26 51.43 28 2124 1914 1742715
Heart rate irregular 90.69 51.43 27 2125 1665 1742964
Fall 90.39 51.43 61 2091 27153 1717476
Loss of consciousness 89.93 51.43 49 2103 14826 1729803
Atrioventricular block first degree 87.06 51.43 23 2129 913 1743716
Visual impairment 85.31 51.43 36 2116 6182 1738447
Dissociation 85.21 51.43 18 2134 264 1744365
Paraesthesia 84.91 51.43 42 2110 10409 1734220
Feeling abnormal 82.27 51.43 42 2110 11124 1733505
Ventricular fibrillation 81.62 51.43 28 2124 2728 1741901
Oedema 81.47 51.43 36 2116 6912 1737717
Dyspnoea exertional 81.00 51.43 31 2121 4130 1740499
Xanthopsia 80.28 51.43 13 2139 35 1744594
Blood potassium increased 80.00 51.43 27 2125 2503 1742126
Nodal arrhythmia 78.94 51.43 16 2136 189 1744440
Ventricular arrhythmia 78.40 51.43 20 2132 690 1743939
Drug ineffective 78.02 51.43 80 2072 63721 1680908
Palpitations 75.70 51.43 34 2118 6780 1737849
Adverse drug reaction 70.24 51.43 29 2123 4709 1739920
Electrocardiogram ST segment depression 69.57 51.43 17 2135 490 1744139
Cardiogenic shock 69.05 51.43 24 2128 2430 1742199
Premature baby 68.49 51.43 25 2127 2917 1741712
Blood urea increased 67.01 51.43 28 2124 4683 1739946
Lethargy 64.69 51.43 31 2121 7153 1737476
Abnormal loss of weight 63.87 51.43 16 2136 512 1744117
Ejection fraction decreased 63.33 51.43 22 2130 2223 1742406
Sinus bradycardia 62.56 51.43 21 2131 1912 1742717
Serotonin syndrome 62.34 51.43 23 2129 2765 1741864
Heart rate increased 61.39 51.43 29 2123 6481 1738148
Left ventricular failure 59.39 51.43 16 2136 684 1743945
Electrocardiogram abnormal 59.14 51.43 18 2134 1195 1743434
Bradyarrhythmia 58.52 51.43 14 2138 368 1744261
Tachycardia 58.50 51.43 35 2117 12593 1732036
Medication error 56.93 51.43 25 2127 4718 1739911
Bundle branch block left 56.75 51.43 16 2136 811 1743818
Atrial tachycardia 56.29 51.43 13 2139 292 1744337
Conduction disorder 52.85 51.43 13 2139 385 1744244
Seizure 51.96 51.43 39 2113 20402 1724227

Pharmacologic Action:

SourceCodeDescription
ATC C01AA05 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
CARDIAC GLYCOSIDES
Digitalis glycosides
FDA EPC N0000175568 Cardiac Glycoside
FDA CS M0003451 Cardiac 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

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Poisoning by digitalis glycoside indication 12876009
Chronic heart failure indication 48447003
Atrial fibrillation indication 49436004 DOID:0060224
Senile cardiac amyloidosis contraindication 16573007
Myocardial infarction contraindication 22298006 DOID:5844
Sick sinus syndrome contraindication 36083008 DOID:13884
Myxedema contraindication 43153006 DOID:11634
Hypokalemia contraindication 43339004
Sinus bradycardia contraindication 49710005
Myocarditis contraindication 50920009 DOID:820
Acute nephropathy contraindication 58574008
Hypercalcemia contraindication 66931009 DOID:12678
Ventricular fibrillation contraindication 71908006
Wolff-Parkinson-White pattern contraindication 74390002 DOID:384
Cor pulmonale contraindication 83291003 DOID:8515
Constrictive pericarditis contraindication 85598007 DOID:11481
Kidney disease contraindication 90708001 DOID:557
Hypomagnesemia contraindication 190855004
Atrioventricular block contraindication 233917008 DOID:0050820
Idiopathic hypertrophic subaortic stenosis contraindication 360465008
Restrictive cardiomyopathy contraindication 415295002 DOID:397

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
0.05MG/ML DIGOXIN VISTAPHARM A213000 Oct. 4, 2019 RX ELIXIR ORAL April 1, 2020 COMPETITIVE GENERIC THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sodium/potassium-transporting ATPase Transporter INHIBITOR IC50 6.40 CHEMBL CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.14 WOMBAT-PK
Signal transducer and activator of transcription 3 Transcription factor IC50 5.73 CHEMBL
Nuclear receptor ROR-gamma Nuclear hormone receptor IC50 5.70 CHEMBL
Sodium/potassium-transporting ATPase subunit alpha-1 Transporter IC50 6.30 CHEMBL
Sodium/potassium-transporting ATPase subunit alpha-2 Ion channel IC50 5.78 DRUG MATRIX
Nuclear receptor ROR-gamma Unclassified IC50 5.70 CHEMBL

External reference:

IDSource
D004077 MESH_DESCRIPTOR_UI
4018047 VUID
N0000146388 NUI
C0012265 UMLSCUI
D00298 KEGG_DRUG
73K4184T59 UNII
389 INN_ID
1413 MMSL
3407 RXNORM
387461009 SNOMEDCT_US
4597 MMSL
d00210 MMSL
796001 SNOMEDCT_US
4018047 VANDF
000593 NDDF
DB00390 DRUGBANK_ID
CHEMBL1751 ChEMBL_ID
DGX PDB_CHEM_ID
CHEBI:145795 CHEBI
4726 IUPHAR_LIGAND_ID
2724385 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0054-0057 SOLUTION 0.05 mg ORAL NDA 17 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0115-9811 TABLET 125 ug ORAL ANDA 17 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0115-9822 TABLET 250 ug ORAL ANDA 17 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0143-1240 TABLET 125 ug ORAL ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0143-1241 TABLET 250 ug ORAL ANDA 16 sections
DIGITEK HUMAN PRESCRIPTION DRUG LABEL 1 0378-6155 TABLET 0.13 mg ORAL ANDA 16 sections
DIGITEK HUMAN PRESCRIPTION DRUG LABEL 1 0378-6156 TABLET 0.25 mg ORAL ANDA 16 sections
DIGOX HUMAN PRESCRIPTION DRUG LABEL 1 0527-1324 TABLET 125 ug ORAL ANDA 11 sections
DIGOX HUMAN PRESCRIPTION DRUG LABEL 1 0527-1325 TABLET 250 ug ORAL ANDA 11 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0615-0518 TABLET 250 ug ORAL ANDA 12 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0615-0547 TABLET 0.13 mg ORAL ANDA 12 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0615-7729 TABLET 125 ug ORAL ANDA 11 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0615-7730 TABLET 250 ug ORAL ANDA 11 sections
DIGOXIN HUMAN PRESCRIPTION DRUG LABEL 1 0615-7935 TABLET 0.13 mg ORAL NDA AUTHORIZED GENERIC 17 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0615-8202 TABLET 125 ug ORAL ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0641-1410 INJECTION 0.25 mg INTRAMUSCULAR ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0641-6184 INJECTION 0.25 mg INTRAMUSCULAR ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0781-3059 INJECTION, SOLUTION 250 ug INTRAMUSCULAR ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0904-5921 TABLET 125 ug ORAL ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0904-5922 TABLET 250 ug ORAL ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 0904-6886 TABLET 125 ug ORAL ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 16714-590 TABLET 125 ug ORAL ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 16714-591 TABLET 250 ug ORAL ANDA 16 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 17856-0057 SOLUTION 0.05 mg ORAL NDA 15 sections
Digoxin HUMAN PRESCRIPTION DRUG LABEL 1 21695-678 TABLET 0.13 mg ORAL ANDA 17 sections
LANOXIN HUMAN PRESCRIPTION DRUG LABEL 1 24987-262 INJECTION, SOLUTION 100 ug INTRAMUSCULAR NDA 11 sections
DIGITEK HUMAN PRESCRIPTION DRUG LABEL 1 42292-002 TABLET 0.25 mg ORAL ANDA 16 sections
DIGITEK HUMAN PRESCRIPTION DRUG LABEL 1 42292-003 TABLET 0.13 mg ORAL ANDA 16 sections
DIGOXIN HUMAN PRESCRIPTION DRUG LABEL 1 49884-494 TABLET 0.25 mg ORAL NDA AUTHORIZED GENERIC 17 sections
DIGOX HUMAN PRESCRIPTION DRUG LABEL 1 49999-181 TABLET 250 ug ORAL ANDA 10 sections