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

Stem definitionDrug idCAS RN
uridine derivatives used as antiviral agents and as antineoplastics 2478 3056-17-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • zerit
  • stavudine
  • sanilvudine
  • staduvine
A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.
  • Molecular weight: 224.22
  • Formula: C10H12N2O4
  • CLOGP: -0.74
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 78.87
  • ALOGS: -0.74
  • ROTB: 2
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
80 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 83 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 39 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.95 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 82 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.67 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 8.20 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 1 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.40 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -0.861 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 4.909 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 2.109 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 2.280 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 92.750 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 93.110 % High 1
herg hERG pIC50 3.741 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.230 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.133 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 90.420 % High 1
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK1,JAK2,MAP3K21,MAP3K7,MAPK7,MAPK9,MARK4,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PIK3CD,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1 43
kinase-selectivity-class AXL,CDK9,GRK2,MAP2K6,PRKDC,TEK 6
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.223 High 1
mh-clint Mouse hepatocyte intrinsic clearance 0.647 High 1
mppb Mouse plasma protein binding (% unbound) 92.920 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 4.102 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 High 1
pppb Pig plasma protein binding (% unbound) 93.240 % High 1
rh-clint Rat hepatocyte intrinsic clearance 0.920 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 96.910 % High 1
rppb Rat plasma protein binding (% unbound) 87.990 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 974.990 uM High 1

Approvals:

DateAgencyCompanyOrphan
June 24, 1994 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
Viral mutation identified 532.30 59.76 81 1827 1944 90624595
Drug resistance 475.46 59.76 113 1795 30336 90596203
Virologic failure 465.15 59.76 73 1835 2151 90624388
Pregnancy 364.24 59.76 106 1802 61941 90564598
Pathogen resistance 234.78 59.76 50 1858 8065 90618474
Lipodystrophy acquired 203.40 59.76 34 1874 1480 90625059
Foetal exposure during pregnancy 201.98 59.76 62 1846 42913 90583626
Caesarean section 169.46 59.76 45 1863 18532 90608007
Abortion induced 148.46 59.76 37 1871 11851 90614688
Acquired gene mutation 92.72 59.76 17 1891 1262 90625277
Pregnancy on contraceptive 92.51 59.76 17 1891 1278 90625261
Lactic acidosis 92.21 59.76 36 1872 50427 90576112
Premature delivery 82.81 59.76 31 1877 38731 90587808
Fat tissue increased 67.15 59.76 12 1896 770 90625769
Hypertriglyceridaemia 66.59 59.76 18 1890 7871 90618668
Portal hypertension 65.53 59.76 16 1892 4685 90621854
Treatment noncompliance 64.19 59.76 28 1880 51699 90574840
Premature baby 60.71 59.76 22 1886 25055 90601484

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
Lipodystrophy acquired 832.67 43.20 155 3200 3295 42614685
Mitochondrial toxicity 704.53 43.20 129 3226 2486 42615494
Eyelid ptosis 562.11 43.20 125 3230 6536 42611444
Diplopia 419.36 43.20 124 3231 20192 42597788
Progressive external ophthalmoplegia 369.17 43.20 68 3287 1343 42616637
Virologic failure 331.26 43.20 74 3281 3920 42614060
Viral mutation identified 288.71 43.20 64 3291 3267 42614713
Foetal exposure during pregnancy 261.03 43.20 108 3247 47203 42570777
Drug resistance 222.52 43.20 88 3267 34160 42583820
Pathogen resistance 197.55 43.20 61 3294 11389 42606591
Ophthalmoplegia 145.86 43.20 34 3321 2166 42615814
Hepatic fibrosis 119.03 43.20 34 3321 4838 42613142
Blood lactic acid increased 106.26 43.20 35 3320 8004 42609976
Multiple-drug resistance 105.37 43.20 34 3321 7288 42610692
Drug-induced liver injury 85.43 43.20 47 3308 38226 42579754
Dysphagia 84.79 43.20 59 3296 72660 42545320
Hypertriglyceridaemia 79.76 43.20 30 3325 10096 42607884
Dyslipidaemia 78.19 43.20 29 3326 9389 42608591
Acquired gene mutation 66.77 43.20 17 3338 1563 42616417
Premature baby 61.66 43.20 32 3323 23121 42594859
Mitochondrial myopathy 54.32 43.20 10 3345 195 42617785
Trisomy 21 49.36 43.20 11 3344 571 42617409
Treatment failure 46.77 43.20 39 3316 62585 42555395

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
Lipodystrophy acquired 1063.96 40.40 179 4135 4345 110580640
Mitochondrial toxicity 815.50 40.40 136 4178 3109 110581876
Virologic failure 673.09 40.40 123 4191 4829 110580156
Viral mutation identified 589.07 40.40 108 4206 4311 110580674
Eyelid ptosis 557.14 40.40 124 4190 13203 110571782
Drug resistance 552.77 40.40 165 4149 56209 110528776
Progressive external ophthalmoplegia 416.26 40.40 68 4246 1352 110583633
Diplopia 411.84 40.40 123 4191 41771 110543214
Pregnancy 271.27 40.40 94 4220 50973 110534012
Pathogen resistance 250.05 40.40 69 4245 17603 110567382
Acquired gene mutation 161.99 40.40 34 4280 2720 110582265
Ophthalmoplegia 147.89 40.40 33 4281 3517 110581468
Hepatic fibrosis 135.10 40.40 36 4278 8030 110576955
Abortion induced 130.57 40.40 35 4279 7984 110577001
Caesarean section 128.69 40.40 39 4275 13778 110571207
Dyslipidaemia 123.14 40.40 39 4275 15926 110569059
Multiple-drug resistance 117.47 40.40 36 4278 13199 110571786
Portal hypertension 105.11 40.40 30 4284 8607 110576378
Immune reconstitution inflammatory syndrome 90.37 40.40 31 4283 16195 110568790
Dysphagia 86.89 40.40 61 4253 153539 110431446
Foetal exposure during pregnancy 86.55 40.40 25 4289 7480 110577505
Pregnancy on contraceptive 86.25 40.40 17 4297 991 110583994
Drug-induced liver injury 82.99 40.40 54 4260 120013 110464972
Lactic acidosis 74.76 40.40 46 4268 92765 110492220
Fat tissue increased 66.99 40.40 14 4300 1094 110583891
Treatment noncompliance 66.07 40.40 39 4275 72951 110512034
Premature delivery 64.77 40.40 29 4285 30603 110554382
Hypertriglyceridaemia 60.43 40.40 23 4291 16131 110568854
Treatment failure 57.39 40.40 62 4252 277172 110307813
Pulmonary tuberculosis 56.94 40.40 19 4295 9120 110575865
Gene mutation 55.96 40.40 15 4299 3414 110581571
Blood lactic acid increased 53.74 40.40 21 4293 15800 110569185
Mitochondrial myopathy 53.39 40.40 10 4304 444 110584541
CD4 lymphocytes decreased 53.24 40.40 14 4300 2960 110582025
Tuberculoma of central nervous system 50.33 40.40 10 4304 607 110584378
Stillbirth 48.25 40.40 14 4300 4250 110580735
Pinealoblastoma 47.66 40.40 7 4307 66 110584919
Blood HIV RNA increased 42.55 40.40 11 4303 2177 110582808
Normal newborn 40.83 40.40 19 4295 21877 110563108

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AF04 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Nucleoside and nucleotide reverse transcriptase inhibitors
ATC J05AR07 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR28 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
FDA MoA N0000009947 Nucleoside Reverse Transcriptase Inhibitors
FDA EXT N0000175459 Nucleoside Analog
FDA EPC N0000175462 Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000963 Antimetabolites
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D018894 Reverse Transcriptase Inhibitors
MeSH PA D019380 Anti-HIV Agents
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:59897 EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent

Related Drugs by ATC class:

J05AF Nucleoside and nucleotide reverse transcriptase inhibitors 12 drugs
abacaviradefovir dipivoxilclevudinedidanosineemtricitabineentecavirlamivudinetelbivudinetenofovir alafenamidetenofovir disoproxilzalcitabinezidovudine
J05AR Antivirals for treatment of HIV infections, combinations 19 drugs
abacaviratazanavirbictegravircobicistatdarunavirdolutegravirdoravirineefavirenzelvitegraviremtricitabinelamivudinelopinavir show all 19 →

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

DiseaseRelationSNOMED_IDDOID
Human immunodeficiency virus infection indication 86406008 DOID:526
Prevention of HIV Infection after Exposure off-label use
Alcoholism contraindication 7200002
Diabetes mellitus contraindication 73211009 DOID:9351
Hyperglycemia contraindication 80394007 DOID:4195
Kidney disease contraindication 90708001 DOID:557
Lactic acidosis contraindication 91273001 DOID:3650
Steatosis of liver contraindication 197321007
Acute pancreatitis contraindication 197456007 DOID:2913
Chronic pancreatitis contraindication 235494005
Disease of liver contraindication 235856003 DOID:409
Peripheral nerve disease contraindication 302226006
Breastfeeding (mother) contraindication 413712001
Obesity contraindication 414916001 DOID:9970




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.3 acidic
pKa2 13.25 acidic

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
Reverse transcriptase/RNaseH Enzyme INHIBITOR EC50 7.30 CHEMBL CHEMBL
Gag-Pol polyprotein Polyprotein WOMBAT-PK
Reverse transcriptase Enzyme IC50 7.22 CHEMBL

External reference:

IDSource
D00445 KEGG_DRUG
4020865 VANDF
C0164662 UMLSCUI
CHEBI:63581 CHEBI
CHEMBL991 ChEMBL_ID
DB00649 DRUGBANK_ID
D018119 MESH_DESCRIPTOR_UI
18283 PUBCHEM_CID
12678 IUPHAR_LIGAND_ID
6775 INN_ID
BO9LE4QFZF UNII
203748 RXNORM
1468 MMSL
159782 MMSL
5512 MMSL
d03773 MMSL
004502 NDDF
108690008 SNOMEDCT_US
386895008 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Stavudine HUMAN PRESCRIPTION DRUG LABEL 1 53808-0594 CAPSULE 40 mg ORAL ANDA 25 sections
Stavudine HUMAN PRESCRIPTION DRUG LABEL 1 53808-0595 CAPSULE 40 mg ORAL ANDA 25 sections
ZERIT HUMAN PRESCRIPTION DRUG LABEL 1 53808-0656 CAPSULE, GELATIN COATED 20 mg ORAL NDA 24 sections
ZERIT HUMAN PRESCRIPTION DRUG LABEL 1 53808-0657 CAPSULE, GELATIN COATED 30 mg ORAL NDA 24 sections
ZERIT HUMAN PRESCRIPTION DRUG LABEL 1 53808-0795 CAPSULE, GELATIN COATED 40 mg ORAL NDA 24 sections
Stavudine HUMAN PRESCRIPTION DRUG LABEL 1 53808-0852 CAPSULE 20 mg ORAL ANDA 30 sections