stavudine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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: -0.49
  • 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 ┬ÁM/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

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
Pregnancy 458.18 30.32 149 4356 26988 46654569
Drug resistance 378.66 30.32 116 4389 17252 46664305
Viral mutation identified 370.87 30.32 74 4431 1825 46679732
Lipodystrophy acquired 350.79 30.32 68 4437 1437 46680120
Virologic failure 294.82 30.32 62 4443 1993 46679564
Lactic acidosis 253.20 30.32 102 4403 33807 46647750
Immune reconstitution inflammatory syndrome 222.21 30.32 60 4445 5665 46675892
Pathogen resistance 155.61 30.32 46 4459 6014 46675543
Caesarean section 152.13 30.32 58 4447 16545 46665012
Mitochondrial toxicity 147.13 30.32 26 4479 321 46681236
Exposure during pregnancy 144.16 30.32 103 4402 108109 46573448
Hypertriglyceridaemia 140.80 30.32 42 4463 5662 46675895
Abortion induced 135.65 30.32 47 4458 10213 46671344
Foetal exposure during pregnancy 129.81 30.32 62 4443 30685 46650872
Portal hypertension 118.82 30.32 33 4472 3450 46678107
Blood lactic acid increased 115.49 30.32 36 4469 5621 46675936
Abortion spontaneous 112.03 30.32 63 4442 43583 46637974
Hyperlactacidaemia 108.81 30.32 28 4477 2187 46679370
Stillbirth 90.69 30.32 31 4474 6460 46675097
Normal newborn 89.10 30.32 30 4475 5971 46675586
Live birth 80.11 30.32 32 4473 10298 46671259
Acquired gene mutation 79.24 30.32 17 4488 599 46680958
Pregnancy on contraceptive 69.33 30.32 17 4488 1090 46680467
Lipoatrophy 64.55 30.32 13 4492 334 46681223
Fat tissue increased 57.77 30.32 13 4492 573 46680984
Premature delivery 56.94 30.32 32 4473 22037 46659520
Premature baby 54.29 30.32 29 4476 18083 46663474
Premature rupture of membranes 49.81 30.32 18 4487 4405 46677152
Premature labour 45.24 30.32 22 4483 11277 46670280
Hepatomegaly 42.34 30.32 21 4484 11232 46670325
Maternal exposure during pregnancy 37.86 30.32 48 4457 102501 46579056
Mitochondrial cytopathy 36.85 30.32 8 4497 298 46681259
CD4 lymphocytes decreased 36.03 30.32 11 4494 1599 46679958
Dyslipidaemia 35.57 30.32 15 4490 5525 46676032
Foetal death 34.93 30.32 17 4488 8726 46672831
Viral load increased 33.37 30.32 10 4495 1365 46680192
Pain 32.45 30.32 4 4501 476944 46204613
Nodular regenerative hyperplasia 32.13 30.32 7 4498 265 46681292
Treatment noncompliance 32.05 30.32 25 4480 29706 46651851
Tuberculoma of central nervous system 31.38 30.32 7 4498 296 46681261
Pulmonary tuberculosis 31.01 30.32 13 4492 4718 46676839
Blood HIV RNULL increased 30.42 30.32 8 4497 679 46680878

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 981.87 18.61 227 9226 3333 29939692
Mitochondrial toxicity 617.31 18.61 146 9307 2368 29940657
Eyelid ptosis 476.54 18.61 138 9315 5050 29937975
Immune reconstitution inflammatory syndrome 443.39 18.61 149 9304 8952 29934073
Diplopia 303.37 18.61 126 9327 13646 29929379
Progressive external ophthalmoplegia 292.27 18.61 70 9383 1196 29941829
Hypertriglyceridaemia 237.07 18.61 91 9362 8007 29935018
Lipoatrophy 229.38 18.61 50 9403 547 29942478
Virologic failure 227.56 18.61 70 9383 3149 29939876
Drug resistance 210.58 18.61 110 9343 20023 29923002
Blood lactic acid increased 201.50 18.61 74 9379 5756 29937269
Foetal exposure during pregnancy 147.00 18.61 109 9344 36762 29906263
Hyperlactacidaemia 136.02 18.61 45 9408 2561 29940464
Kaposi's sarcoma 133.92 18.61 36 9417 992 29942033
Lactic acidosis 130.54 18.61 95 9358 31118 29911907
Viral mutation identified 123.79 18.61 42 9411 2584 29940441
Osteonecrosis 121.41 18.61 71 9382 16064 29926961
Hyperlipidaemia 120.21 18.61 67 9386 13840 29929185
Hepatic fibrosis 103.88 18.61 40 9413 3540 29939485
Ophthalmoplegia 103.44 18.61 31 9422 1273 29941752
Portal hypertension 97.35 18.61 39 9414 3834 29939191
Facial wasting 93.16 18.61 19 9434 146 29942879
Extraocular muscle paresis 78.55 18.61 20 9433 443 29942582
Pathogen resistance 71.24 18.61 40 9413 8370 29934655
Blood triglycerides increased 66.23 18.61 46 9407 13971 29929054
Cytomegalovirus chorioretinitis 62.22 18.61 27 9426 3241 29939784
Blood bilirubin unconjugated increased 61.80 18.61 18 9435 668 29942357
HIV infection 60.67 18.61 22 9431 1646 29941379
Pregnancy 59.87 18.61 14 9439 214 29942811
Off label use 57.52 18.61 6 9447 249284 29693741
Dyslipidaemia 53.33 18.61 29 9424 5698 29937327
Premature baby 52.63 18.61 43 9410 16648 29926377
Drug-induced liver injury 51.26 18.61 47 9406 21227 29921798
Hepatic function abnormal 50.23 18.61 64 9389 41881 29901144
Acquired gene mutation 48.61 18.61 17 9436 1144 29941881
Hepatic cirrhosis 45.84 18.61 39 9414 15960 29927065
Trisomy 21 45.39 18.61 13 9440 454 29942571
Neonatal disorder 44.38 18.61 15 9438 911 29942114
Hypotension 43.34 18.61 6 9447 200559 29742466
CD4 lymphocytes decreased 42.36 18.61 18 9435 2052 29940973
Hepatitis B 41.16 18.61 25 9428 6047 29936978
Drug ineffective 40.78 18.61 29 9424 340358 29602667
Blood pyruvic acid increased 40.53 18.61 7 9446 18 29943007
Meningitis cryptococcal 39.44 18.61 17 9436 2007 29941018
Multiple-drug resistance 39.31 18.61 19 9434 2922 29940103
Basedow's disease 38.94 18.61 8 9445 64 29942961
Anaemia macrocytic 38.69 18.61 18 9435 2542 29940483
Progressive multifocal leukoencephalopathy 36.64 18.61 27 9426 8986 29934039
Varices oesophageal 36.13 18.61 19 9434 3490 29939535
Pneumocystis jirovecii pneumonia 35.84 18.61 35 9418 17085 29925940
Pulmonary tuberculosis 35.52 18.61 21 9432 4836 29938189
Nodular regenerative hyperplasia 35.29 18.61 12 9441 742 29942283
Fat tissue increased 34.98 18.61 10 9443 347 29942678
Gynaecomastia 33.91 18.61 25 9428 8326 29934699
Exposure during pregnancy 33.78 18.61 26 9427 9235 29933790
Oesophageal candidiasis 32.89 18.61 19 9434 4191 29938834
Opportunistic infection 32.31 18.61 13 9440 1291 29941734
Foetal distress syndrome 32.09 18.61 12 9441 979 29942046
Hepatomegaly 31.91 18.61 26 9427 10021 29933004
Fall 31.85 18.61 9 9444 181863 29761162
Pinealoblastoma 31.73 18.61 8 9445 170 29942855
Mycobacterium avium complex infection 31.73 18.61 16 9437 2695 29940330
Lipohypertrophy 31.35 18.61 9 9444 317 29942708
Viral load increased 30.95 18.61 16 9437 2838 29940187
Aspartate aminotransferase increased 29.35 18.61 63 9390 63359 29879666
Neuropathy peripheral 29.23 18.61 67 9386 70408 29872617
Enophthalmos 28.91 18.61 5 9448 13 29943012
Liver disorder 28.91 18.61 41 9412 29681 29913344
Ascites 28.44 18.61 45 9408 35876 29907149
Hepatic failure 27.43 18.61 43 9410 34000 29909025
Oesophageal varices haemorrhage 27.16 18.61 15 9438 3036 29939989
Atypical mycobacterial infection 27.07 18.61 10 9443 788 29942237
Hypercholesterolaemia 27.00 18.61 21 9432 7571 29935454
Mitochondrial myopathy 26.99 18.61 7 9446 167 29942858
Gamma-glutamyltransferase increased 26.37 18.61 39 9414 29311 29913714
Fanconi syndrome acquired 26.35 18.61 13 9440 2090 29940935
Caesarean section 26.15 18.61 13 9440 2124 29940901
Heart transplant rejection 25.98 18.61 11 9442 1242 29941783
Lymphadenopathy 25.76 18.61 35 9418 24341 29918684
Mitochondrial cytopathy 25.59 18.61 7 9446 206 29942819
Amylase increased 24.88 18.61 18 9435 5823 29937202
Death 24.86 18.61 47 9406 357236 29585789
Low set ears 24.85 18.61 8 9445 417 29942608
Dysphagia 24.73 18.61 55 9398 56643 29886382
Hepatosplenomegaly 24.47 18.61 15 9438 3686 29939339
Treatment failure 24.14 18.61 41 9412 34638 29908387
Pancreatitis 23.91 18.61 42 9411 36448 29906577
Pneumonia 23.23 18.61 44 9409 334262 29608763
Mycobacterium avium complex immune restoration disease 22.90 18.61 5 9448 55 29942970
HIV-associated neurocognitive disorder 22.34 18.61 7 9446 334 29942691
Hepatitis C 22.21 18.61 24 9429 13181 29929844
Diabetes mellitus 22.20 18.61 44 9409 41821 29901204
Musculoskeletal toxicity 21.79 18.61 5 9448 70 29942955
Tuberculosis 21.73 18.61 19 9434 8058 29934967
Blood insulin increased 21.59 18.61 7 9446 373 29942652
Small for dates baby 21.20 18.61 13 9440 3195 29939830
Cerebral toxoplasmosis 21.16 18.61 10 9443 1462 29941563
Lagophthalmos 20.67 18.61 5 9448 89 29942936
Anal cancer 20.58 18.61 7 9446 433 29942592
Dyspnoea 20.51 18.61 47 9406 333248 29609777
Protrusion tongue 20.39 18.61 6 9447 231 29942794
Oral candidiasis 20.17 18.61 21 9432 11050 29931975
Eyelid function disorder 20.06 18.61 4 9449 27 29942998
Hepatic steatosis 19.98 18.61 24 9429 14769 29928256
Cardiac arrest 19.50 18.61 3 9450 92847 29850178
Molluscum contagiosum 19.40 18.61 6 9447 274 29942751
Meconium ileus 19.25 18.61 4 9449 34 29942991
Febrile neutropenia 19.18 18.61 5 9448 106688 29836337
Anaemia neonatal 19.07 18.61 6 9447 290 29942735
Central pain syndrome 18.80 18.61 5 9448 132 29942893
Pancreatitis acute 18.71 18.61 31 9422 25664 29917361

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
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 D019380 Anti-HIV Agents
MeSH PA D000890 Anti-Infective Agents
MeSH PA D044966 Anti-Retroviral Agents
MeSH PA D000963 Antimetabolites
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D009676 Noxae
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors
MeSH PA D018894 Reverse Transcriptase Inhibitors
CHEBI has role CHEBI:22587 antiviral agents
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:59897 rna-dependent dna polymerase inhibitors

Drug Use (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

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
D018119 MESH_DESCRIPTOR_UI
6775 INN_ID
DB00649 DRUGBANK_ID
BO9LE4QFZF UNII
18283 PUBCHEM_CID
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 31722-515 CAPSULE 15 mg ORAL ANDA 25 sections
Stavudine HUMAN PRESCRIPTION DRUG LABEL 1 31722-516 CAPSULE 20 mg ORAL ANDA 25 sections
Stavudine HUMAN PRESCRIPTION DRUG LABEL 1 31722-517 CAPSULE 30 mg ORAL ANDA 25 sections
Stavudine HUMAN PRESCRIPTION DRUG LABEL 1 31722-518 CAPSULE 40 mg ORAL ANDA 25 sections
stavudine HUMAN PRESCRIPTION DRUG LABEL 1 53104-0111 FOR SOLUTION 1 mg ORAL ANDA 26 sections
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