entecavir ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antivirals carbocyclic nucleosides 1019 142217-69-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • entecavir monohydrate
  • anhydrous entecavir
  • BMS-200475-01
  • entecavir
  • baraclude
  • entecavir hydrate
Entecavir, a guanosine nucleoside analogue with activity against HBV reverse transcriptase, is efficiently phosphorylated to the active triphosphate form, which has an intracellular half-life of 15 hours. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate functionally inhibits all three activities of the HBV reverse transcriptase: (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Entecavir triphosphate is a weak inhibitor of cellular DNA polymerases alpha, beta, and delta and mitochondrial DNA polymerase gamma with Ki values ranging from 18 to > 160 microM.
  • Molecular weight: 277.28
  • Formula: C12H15N5O3
  • CLOGP: -1.78
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 4
  • TPSA: 125.76
  • ALOGS: -1.63
  • ROTB: 2

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
0.50 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 2.40 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 70 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.05 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 99 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
March 29, 2005 FDA BRISTOL MYERS SQUIBB

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
Drug resistance 145.72 21.17 56 4156 18933 50581979
Hepatitis B reactivation 135.21 21.17 32 4180 2055 50598857
Hepatitis B DNA increased 110.62 21.17 18 4194 153 50600759
Viral load increased 102.98 21.17 23 4189 1140 50599772
Hepatitis B 100.49 21.17 28 4184 3438 50597474
Hepatocellular carcinoma 85.68 21.17 22 4190 1977 50598935
Exposure via body fluid 80.67 21.17 16 4196 443 50600469
Hypophosphataemia 65.15 21.17 25 4187 8389 50592523
Abortion induced 55.74 21.17 23 4189 9321 50591591
Hepatic cancer 53.57 21.17 17 4195 3258 50597654
Viral mutation identified 51.08 21.17 14 4198 1615 50599297
Liver transplant 43.02 21.17 13 4199 2119 50598793
Osteomalacia 41.93 21.17 10 4202 662 50600250
Pathogen resistance 40.83 21.17 16 4196 5673 50595239
Hepatic failure 40.39 21.17 28 4184 32255 50568657
Fanconi syndrome acquired 38.78 21.17 10 4202 913 50599999
Hepatic function abnormal 37.76 21.17 27 4185 32654 50568258
Maternal exposure during pregnancy 32.38 21.17 52 4160 159726 50441186
Febrile neutropenia 28.84 21.17 38 4174 97629 50503283
Pregnancy on contraceptive 28.21 21.17 8 4204 1044 50599868
Neutropenia 27.07 21.17 46 4166 147919 50452993
Hepatic encephalopathy 26.86 21.17 14 4198 9622 50591290
Abortion spontaneous 25.89 21.17 24 4188 41748 50559164
Cryoglobulinaemia 24.62 21.17 6 4206 435 50600477
Neutrophil count decreased 23.92 21.17 24 4188 46002 50554910
Platelet count decreased 23.49 21.17 35 4177 100691 50500221
Fanconi syndrome 23.23 21.17 7 4205 1129 50599783
Leukopenia 22.64 21.17 28 4184 67500 50533412
Viral uveitis 22.19 21.17 4 4208 65 50600847
Gastroenteritis staphylococcal 21.75 21.17 4 4208 73 50600839
Genotype drug resistance test positive 21.69 21.17 5 4207 285 50600627
Renal impairment 21.65 21.17 29 4183 75632 50525280

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
Drug resistance 312.90 17.04 145 8773 21395 29544214
Hepatocellular carcinoma 299.57 17.04 103 8815 6935 29558674
Viral mutation identified 271.42 17.04 75 8843 2413 29563196
Hepatic cancer 261.26 17.04 91 8827 6365 29559244
Hepatic failure 186.90 17.04 117 8801 31395 29534214
Hepatitis B DNA increased 183.63 17.04 40 8878 458 29565151
Genotype drug resistance test 178.99 17.04 29 8889 45 29565564
Hepatitis B reactivation 172.06 17.04 56 8862 3173 29562436
Pathogen resistance 128.22 17.04 58 8860 8058 29557551
Hepatitis B 125.54 17.04 51 8867 5446 29560163
Viral load increased 111.03 17.04 36 8882 2013 29563596
Multiple-drug resistance 109.44 17.04 42 8876 3858 29561751
Osteomalacia 107.57 17.04 29 8889 847 29564762
Fanconi syndrome acquired 106.51 17.04 34 8884 1808 29563801
Hepatic encephalopathy 99.52 17.04 57 8861 12978 29552631
Ascites 97.79 17.04 84 8834 36535 29529074
Hepatic cirrhosis 96.68 17.04 58 8860 14386 29551223
Hypophosphataemia 95.52 17.04 47 8871 7877 29557732
Blood HIV RNA decreased 85.29 17.04 12 8906 0 29565609
Hepatic function abnormal 70.03 17.04 72 8846 39187 29526422
Genotype drug resistance test positive 67.97 17.04 21 8897 1002 29564607
Hepatitis B surface antigen positive 61.45 17.04 13 8905 128 29565481
Blood phosphorus decreased 60.71 17.04 25 8893 2760 29562849
Viral infection 50.05 17.04 39 8879 14771 29550838
Osteoporosis 46.81 17.04 33 8885 10736 29554873
Portal vein thrombosis 40.98 17.04 20 8898 3289 29562320
Fanconi syndrome 40.54 17.04 16 8902 1582 29564027
Palmar-plantar erythrodysaesthesia syndrome 39.63 17.04 34 8884 14725 29550884
Alanine aminotransferase increased 38.14 17.04 73 8845 70871 29494738
Blood bilirubin increased 36.55 17.04 48 8870 33845 29531764
Autoimmune haemolytic anaemia 32.53 17.04 18 8900 3830 29561779
Renal impairment 31.28 17.04 73 8845 81260 29484349
Renal tubular injury 28.71 17.04 10 8908 696 29564913
Optic disc hyperaemia 28.43 17.04 4 8914 0 29565609
Hypocalciuria 28.43 17.04 4 8914 0 29565609
Portal vein occlusion 28.10 17.04 6 8912 62 29565547
Mycoplasma infection 27.74 17.04 8 8910 300 29565309
Parotid gland haemorrhage 26.59 17.04 5 8913 25 29565584
Asymptomatic viral hepatitis 26.11 17.04 5 8913 28 29565581
Liver transplant 25.72 17.04 13 8905 2303 29563306
Renal tubular acidosis 25.68 17.04 12 8906 1791 29563818
Retinal toxicity 25.60 17.04 8 8910 396 29565213
Malignant anorectal neoplasm 25.15 17.04 5 8913 35 29565574
Aspartate aminotransferase increased 24.49 17.04 55 8863 59670 29505939
Retinopathy hypertensive 24.39 17.04 7 8911 258 29565351
Retinal depigmentation 24.14 17.04 5 8913 44 29565565
Hepatitis B e antigen positive 23.65 17.04 5 8913 49 29565560
Foetal heart rate abnormal 22.70 17.04 6 8912 162 29565447
Foetal hypokinesia 21.94 17.04 7 8911 371 29565238
Liver transplant rejection 21.69 17.04 11 8907 1963 29563646
Renal glycosuria 21.44 17.04 4 8914 19 29565590
Blood uric acid 21.32 17.04 3 8915 0 29565609
Transaminases increased 21.24 17.04 30 8888 22632 29542977
Blood creatine phosphokinase increased 20.81 17.04 41 8877 40603 29525006
Jaundice 19.36 17.04 33 8885 29263 29536346
Alkalosis hypokalaemic 19.24 17.04 3 8915 3 29565606
Antiviral drug level below therapeutic 19.24 17.04 3 8915 3 29565606
Venoocclusive liver disease 18.70 17.04 16 8902 6901 29558708
Oesophageal varices haemorrhage 18.45 17.04 11 8907 2691 29562918
Schistosomiasis 18.26 17.04 4 8914 47 29565562
Amylase increased 18.04 17.04 14 8904 5266 29560343
Laryngeal erythema 18.03 17.04 3 8915 6 29565603
Hepatitis B antigen positive 18.03 17.04 3 8915 6 29565603
Lipase increased 18.02 17.04 17 8901 8320 29557289
Dyspnoea 17.64 17.04 46 8872 326686 29238923
Completed suicide 17.63 17.04 3 8915 90243 29475366
Malaria 17.28 17.04 5 8913 190 29565419
Mitochondrial myopathy 17.05 17.04 5 8913 199 29565410

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
Hepatocellular carcinoma 364.41 16.48 110 11409 8293 64478920
Hepatic cancer 346.77 16.48 103 11416 7345 64479868
Viral mutation identified 332.34 16.48 84 11435 3262 64483951
Hepatitis B reactivation 287.09 16.48 81 11438 4808 64482405
Drug resistance 268.05 16.48 129 11390 34973 64452240
Hepatitis B DNA increased 242.90 16.48 48 11471 582 64486631
Hepatic failure 233.66 16.48 137 11382 55257 64431956
Pathogen resistance 173.38 16.48 70 11449 12473 64474740
Viral load increased 149.59 16.48 42 11477 2445 64484768
Hypophosphataemia 143.10 16.48 64 11455 14656 64472557
Fanconi syndrome acquired 137.08 16.48 39 11480 2382 64484831
Hepatic encephalopathy 135.68 16.48 69 11450 20997 64466216
Hepatitis B 134.47 16.48 51 11468 7694 64479519
Osteomalacia 128.64 16.48 33 11486 1358 64485855
Multiple-drug resistance 113.54 16.48 43 11476 6459 64480754
Hepatic function abnormal 111.19 16.48 92 11427 64221 64422992
Genotype drug resistance test positive 97.68 16.48 25 11494 1019 64486194
Ascites 97.52 16.48 84 11435 61917 64425296
Hepatic cirrhosis 92.61 16.48 58 11461 26240 64460973
Blood HIV RNA decreased 76.31 16.48 10 11509 0 64487213
Renal impairment 63.77 16.48 98 11421 134919 64352294
Hepatitis B surface antigen positive 59.31 16.48 12 11507 165 64487048
Liver transplant 57.08 16.48 23 11496 4069 64483144
Blood bilirubin increased 56.24 16.48 60 11459 57493 64429720
Portal vein thrombosis 55.95 16.48 24 11495 4967 64482246
Fanconi syndrome 48.99 16.48 18 11501 2483 64484730
Blood phosphorus decreased 46.63 16.48 22 11497 5683 64481530
Alanine aminotransferase increased 45.83 16.48 86 11433 138945 64348268
Palmar-plantar erythrodysaesthesia syndrome 43.16 16.48 38 11481 28781 64458432
Platelet count decreased 41.36 16.48 92 11427 167619 64319594
Jaundice 37.86 16.48 45 11474 48467 64438746
Oesophageal varices haemorrhage 35.96 16.48 16 11503 3613 64483600
Blood creatine phosphokinase increased 34.15 16.48 47 11472 58511 64428702
Liver transplant rejection 32.23 16.48 14 11505 2985 64484228
Abortion induced 30.08 16.48 17 11502 6371 64480842
Parotid gland haemorrhage 29.04 16.48 5 11514 26 64487187
Autoimmune haemolytic anaemia 28.46 16.48 17 11502 7059 64480154
Transaminases increased 27.83 16.48 37 11482 44557 64442656
Portal vein occlusion 27.76 16.48 5 11514 35 64487178
Antiviral drug level below therapeutic 27.18 16.48 5 11514 40 64487173
Blood creatinine increased 26.45 16.48 68 11451 135714 64351499
Osteoporosis 26.39 16.48 35 11484 42045 64445168
Optic disc hyperaemia 25.81 16.48 4 11515 9 64487204
Malignant anorectal neoplasm 25.74 16.48 5 11514 55 64487158
Renal tubular injury 25.15 16.48 9 11510 1152 64486061
Pregnancy on contraceptive 24.44 16.48 8 11511 783 64486430
Retinopathy hypertensive 24.05 16.48 7 11512 463 64486750
Product substitution issue 23.69 16.48 22 11497 17839 64469374
Acute hepatic failure 23.36 16.48 26 11493 26086 64461127
Joint swelling 23.31 16.48 5 11514 215377 64271836
Hypocalciuria 23.20 16.48 4 11515 21 64487192
Blood uric acid 22.89 16.48 3 11516 0 64487213
Renal tubular acidosis 22.86 16.48 11 11508 2968 64484245
Liver disorder 22.76 16.48 37 11482 53314 64433899
Liver abscess 22.06 16.48 13 11506 5267 64481946
Renal glycosuria 21.63 16.48 4 11515 33 64487180
Mycoplasma infection 21.61 16.48 7 11512 663 64486550
Aspartate aminotransferase increased 21.30 16.48 58 11461 119730 64367483
Proteinuria 20.45 16.48 25 11494 27698 64459515
Retinal toxicity 20.38 16.48 8 11511 1322 64485891
Lactic acidosis 20.22 16.48 38 11481 61372 64425841
Hepatectomy 20.11 16.48 5 11514 181 64487032
Therapeutic embolisation 19.69 16.48 6 11513 465 64486748
Schistosomiasis 19.64 16.48 4 11515 57 64487156
Drug hypersensitivity 19.56 16.48 9 11510 237806 64249407
Anxiety 19.45 16.48 6 11513 202643 64284570
Amylase increased 19.14 16.48 15 11504 9670 64477543
Bone pain 18.96 16.48 32 11487 47540 64439673
Venoocclusive liver disease 18.70 16.48 15 11504 10000 64477213
Pain 18.57 16.48 45 11474 553466 63933747
Haemorrhagic cholecystitis 18.55 16.48 4 11515 76 64487137
Multiple organ dysfunction syndrome 17.92 16.48 49 11470 101364 64385849
Mitochondrial myopathy 17.92 16.48 5 11514 284 64486929
Viral uveitis 17.71 16.48 4 11515 95 64487118
Thrombocytopenia 17.70 16.48 83 11436 223718 64263495
Hyperphosphaturia 17.67 16.48 4 11515 96 64487117
White blood cell count decreased 17.55 16.48 65 11454 157772 64329441
Blood alkaline phosphatase increased 17.51 16.48 34 11485 56245 64430968
Retinal depigmentation 17.39 16.48 5 11514 317 64486896
Toxicity to various agents 17.11 16.48 24 11495 363489 64123724
Cancer surgery 16.97 16.48 6 11513 741 64486472
Nasopharyngitis 16.78 16.48 7 11512 196066 64291147
Alkalosis hypokalaemic 16.66 16.48 3 11516 21 64487192
Febrile neutropenia 16.64 16.48 72 11447 187585 64299628
Malaria 16.63 16.48 5 11514 370 64486843
Sinusitis 16.60 16.48 3 11516 145925 64341288
Diffuse large B-cell lymphoma recurrent 16.53 16.48 9 11510 3137 64484076

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AF10 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Nucleoside and nucleotide reverse transcriptase inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
CHEBI has role CHEBI:36044 antiviral drugs
CHEBI has role CHEBI:59897 reverse transcriptase inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic type B viral hepatitis indication 61977001
Lamivudine-Refractory Chronic Hepatitis B indication
Lactic acidosis contraindication 91273001 DOID:3650
Liver function tests abnormal contraindication 166603001
Steatosis of liver contraindication 197321007
Impaired renal function disorder contraindication 197663003
Drug Resistance to Anti-retroviral Therapy contraindication




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 9.56 acidic
pKa2 12.33 acidic
pKa3 13.37 acidic
pKa4 4.58 Basic
pKa5 3.37 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
Protein P Polyprotein INHIBITOR CHEMBL CHEMBL
Protein P Polyprotein WOMBAT-PK
Capsid protein Unclassified EC50 9.62 CHEMBL

External reference:

IDSource
4024911 VUID
N0000171606 NUI
D04008 KEGG_DRUG
4024911 VANDF
C0971023 UMLSCUI
CHEBI:473990 CHEBI
CHEMBL713 ChEMBL_ID
DB00442 DRUGBANK_ID
C413685 MESH_SUPPLEMENTAL_RECORD_UI
135398508 PUBCHEM_CID
5968Y6H45M UNII
1546027 RXNORM
19722 MMSL
228280 MMSL
67562 MMSL
d05525 MMSL
010730 NDDF
416248007 SNOMEDCT_US
416644000 SNOMEDCT_US
725853008 SNOMEDCT_US
209216-23-9 SECONDARY_CAS_RN

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1611 TABLET, FILM COATED 0.50 mg ORAL NDA 28 sections
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1612 TABLET, FILM COATED 1 mg ORAL NDA 28 sections
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1614 SOLUTION 0.05 mg ORAL NDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 10135-615 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 10135-616 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 16714-717 TABLET, FILM COATED 0.50 mg ORAL ANDA 27 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 16714-718 TABLET, FILM COATED 1 mg ORAL ANDA 27 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 16729-388 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 16729-389 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42291-261 TABLET, FILM COATED 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42291-262 TABLET, FILM COATED 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42806-658 TABLET 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42806-659 TABLET 1 mg ORAL ANDA 28 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 50771-013 TABLET, FILM COATED 0.50 mg ORAL ANDA 28 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 50771-014 TABLET, FILM COATED 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51407-064 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51407-065 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51991-895 TABLET 0.50 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51991-895 TABLET 0.50 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51991-896 TABLET 1 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51991-896 TABLET 1 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60050-057 TABLET 0.50 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60050-077 TABLET 1 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60687-216 TABLET 0.50 mg ORAL ANDA 26 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 62227-101 TABLET 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 62227-102 TABLET 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 63126-101 TABLET, FILM COATED 0.50 mg ORAL ANDA 27 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 63126-102 TABLET, FILM COATED 1 mg ORAL ANDA 27 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 65162-446 TABLET, FILM COATED 0.50 mg ORAL ANDA 26 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 65162-449 TABLET, FILM COATED 1 mg ORAL ANDA 26 sections