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

Stem definitionDrug idCAS RN
antivirals 869 69655-05-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • didanosine
  • videx
  • dideoxyinosine
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.
  • Molecular weight: 236.23
  • Formula: C10H12N4O3
  • CLOGP: -1.92
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 2
  • TPSA: 88.74
  • ALOGS: -1.56
  • ROTB: 2

  • Status: OFM

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

Drug dosage:

DoseUnitRoute
0.40 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 27.30 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 55 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 24.19 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 38 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.77 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 11 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.95 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.40 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Oct. 9, 1991 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 439.07 32.47 141 3904 31300 53313721
Viral mutation identified 285.37 32.47 58 3987 2016 53343005
Foetal exposure during pregnancy 235.02 32.47 91 3954 34624 53310397
Portal hypertension 219.78 32.47 52 3993 3676 53341345
Exposure during pregnancy 213.93 32.47 127 3918 124733 53220288
Drug resistance 204.34 32.47 71 3974 19891 53325130
Caesarean section 167.23 32.47 59 3986 17261 53327760
Lipodystrophy acquired 156.84 32.47 34 4011 1616 53343405
Abortion induced 156.59 32.47 50 3995 10776 53334245
Lactic acidosis 148.48 32.47 67 3978 37186 53307835
Abortion spontaneous 146.08 32.47 71 3974 46564 53298457
Stillbirth 134.78 32.47 40 4005 6757 53338264
Hypertriglyceridaemia 124.56 32.47 37 4008 6267 53338754
Virologic failure 104.78 32.47 26 4019 2238 53342783
Pathogen resistance 97.72 32.47 31 4014 6529 53338492
Blood lactic acid increased 96.34 32.47 30 4015 5948 53339073
Premature baby 86.45 32.47 38 4007 19763 53325258
Premature rupture of membranes 80.47 32.47 25 4020 4915 53340106
Retinoblastoma 73.01 32.47 12 4033 121 53344900
Live birth 72.60 32.47 31 4014 15028 53329993
Pancreatitis 71.10 32.47 44 4001 46098 53298923
Premature delivery 70.55 32.47 36 4009 26068 53318953
Foetal death 68.45 32.47 26 4019 9321 53335700
Immune reconstitution inflammatory syndrome 66.49 32.47 23 4022 6323 53338698
Normal newborn 63.71 32.47 23 4022 7156 53337865
Retinal toxicity 61.73 32.47 15 4030 1182 53343839
Varices oesophageal 56.53 32.47 17 4028 2995 53342026
Mitochondrial toxicity 53.99 32.47 11 4034 385 53344636
Amniotic cavity infection 50.89 32.47 13 4032 1257 53343764
Premature labour 45.28 32.47 21 4024 12341 53332680
Nodular regenerative hyperplasia 44.31 32.47 9 4036 310 53344711
Pregnancy on contraceptive 41.41 32.47 11 4034 1238 53343783
Maternal drugs affecting foetus 39.06 32.47 15 4030 5531 53339490
Ventricular septal defect 38.83 32.47 14 4031 4336 53340685
Non-cirrhotic portal hypertension 38.82 32.47 7 4038 126 53344895
Hypophosphataemia 38.73 32.47 17 4028 8788 53336233
CD4 lymphocytes decreased 38.05 32.47 11 4034 1690 53343331
Lipase increased 37.71 32.47 17 4028 9361 53335660
Maternal exposure during pregnancy 35.64 32.47 51 3994 155588 53189433
Viral load increased 35.06 32.47 10 4035 1465 53343556
Neutropenia neonatal 33.82 32.47 6 4039 98 53344923
Fanconi syndrome acquired 33.38 32.47 9 4036 1072 53343949
Portal vein thrombosis 33.37 32.47 11 4034 2608 53342413
Ascites 33.11 32.47 26 4019 39709 53305312
Hyperlactacidaemia 32.94 32.47 11 4034 2714 53342307
Premature separation of placenta 32.73 32.47 10 4035 1857 53343164
Neonatal disorder 32.60 32.47 8 4037 656 53344365

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 861.87 21.94 198 8218 3484 32501626
Mitochondrial toxicity 683.00 21.94 154 8262 2476 32502634
Eyelid ptosis 554.90 21.94 151 8265 5391 32499719
Diplopia 317.74 21.94 125 8291 14387 32490723
Progressive external ophthalmoplegia 292.67 21.94 68 8348 1250 32503860
Portal hypertension 259.28 21.94 78 8338 3986 32501124
Pinealoblastoma 216.46 21.94 38 8378 144 32504966
Foetal exposure during pregnancy 196.32 21.94 126 8290 41175 32463935
Lipoatrophy 189.41 21.94 42 8374 619 32504491
Hepatic fibrosis 170.12 21.94 55 8361 3563 32501547
Retinal toxicity 154.18 21.94 33 8383 408 32504702
Virologic failure 151.67 21.94 51 8365 3736 32501374
Blood lactic acid increased 136.95 21.94 54 8362 6227 32498883
Drug resistance 136.85 21.94 81 8335 22884 32482226
Viral mutation identified 130.22 21.94 43 8373 2976 32502134
Ophthalmoplegia 124.16 21.94 35 8381 1416 32503694
Hypertriglyceridaemia 116.70 21.94 53 8363 8666 32496444
Lactic acidosis 115.68 21.94 84 8332 33452 32471658
Nodular regenerative hyperplasia 115.64 21.94 29 8387 742 32504368
Hyperlactacidaemia 102.10 21.94 36 8380 3038 32502072
Extraocular muscle paresis 94.46 21.94 23 8393 519 32504591
Pathogen resistance 91.25 21.94 46 8370 9464 32495646
Fanconi syndrome 82.82 21.94 27 8389 1793 32503317
Drug-induced liver injury 80.05 21.94 59 8357 24004 32481106
Pancreatitis 71.35 21.94 67 8349 38084 32467026
Varices oesophageal 71.21 21.94 29 8387 3632 32501478
Hyperlipidaemia 70.61 21.94 45 8371 14466 32490644
Fanconi syndrome acquired 69.82 21.94 25 8391 2205 32502905
Osteonecrosis 69.79 21.94 47 8369 16575 32488535
Pregnancy 64.97 21.94 15 8401 267 32504843
Mitochondrial cytopathy 63.13 21.94 14 8402 206 32504904
CD4 lymphocytes decreased 62.77 21.94 23 8393 2167 32502943
Mitochondrial myopathy 62.58 21.94 14 8402 215 32504895
HIV infection 61.84 21.94 22 8394 1904 32503206
Optic nerve neoplasm 58.75 21.94 10 8406 30 32505080
Exposure during pregnancy 58.74 21.94 34 8382 9195 32495915
Oesophageal varices haemorrhage 57.81 21.94 24 8392 3155 32501955
Hepatic cirrhosis 55.40 21.94 41 8375 16768 32488342
Facial wasting 54.67 21.94 12 8404 168 32504942
Congenital neoplasm 52.87 21.94 9 8407 27 32505083
Ascites 52.20 21.94 58 8358 40133 32464977
Dyslipidaemia 50.95 21.94 28 8388 6855 32498255
Gynaecomastia 49.60 21.94 30 8386 8789 32496321
Viral load increased 48.06 21.94 21 8395 3129 32501981
Immune reconstitution inflammatory syndrome 47.38 21.94 30 8386 9529 32495581
Blood antidiuretic hormone increased 45.47 21.94 9 8407 73 32505037
Hepatomegaly 44.91 21.94 30 8386 10427 32494683
Cachexia 44.73 21.94 26 8390 7083 32498027
Pancreatitis acute 41.75 21.94 43 8373 27292 32477818
Portal hypertensive gastropathy 41.04 21.94 12 8404 553 32504557
Renal tubular disorder 40.83 21.94 22 8394 5180 32499930
Lipase increased 40.83 21.94 27 8389 9230 32495880
Off label use 39.56 21.94 15 8401 306305 32198805
Premature baby 39.43 21.94 35 8381 18483 32486627
Strongyloidiasis 38.83 21.94 17 8399 2544 32502566
Kaposi's sarcoma 37.91 21.94 13 8403 1009 32504101
Amylase increased 37.71 21.94 22 8394 6033 32499077
Post streptococcal glomerulonephritis 37.50 21.94 7 8409 40 32505070
Cholestasis 36.80 21.94 40 8376 26993 32478117
Fall 36.75 21.94 4 8412 196197 32308913
Drug interaction 35.18 21.94 130 8286 218055 32287055
Vanishing bile duct syndrome 33.96 21.94 11 8405 715 32504395
Foetal distress syndrome 33.30 21.94 12 8404 1077 32504033
Dysphagia 33.03 21.94 58 8358 61418 32443692
Oesophageal candidiasis 32.79 21.94 18 8398 4396 32500714
Multiple-drug resistance 32.55 21.94 17 8399 3758 32501352
Death 32.29 21.94 31 8385 382486 32122624
Aspartate aminotransferase increased 32.29 21.94 60 8356 66369 32438741
Pneumonia 32.12 21.94 27 8389 355225 32149885
Blood triglycerides increased 31.86 21.94 28 8388 14591 32490519
Neonatal disorder 30.94 21.94 11 8405 950 32504160
Delayed graft function 30.29 21.94 13 8403 1854 32503256
Fat tissue increased 30.25 21.94 9 8407 441 32504669
Glycosuria 30.22 21.94 12 8404 1406 32503704
Erosive duodenitis 29.79 21.94 12 8404 1460 32503650
Hepatic steatosis 29.49 21.94 28 8388 16105 32489005
Gamma-glutamyltransferase increased 29.38 21.94 38 8378 30744 32474366
Hepatitis B 29.19 21.94 19 8397 6322 32498788
Splenomegaly 28.14 21.94 26 8390 14451 32490659
Dyspnoea 27.56 21.94 32 8384 362013 32143097
Portal vein thrombosis 27.11 21.94 15 8401 3720 32501390
Liver disorder 27.02 21.94 37 8379 31617 32473493
Hypothalamic pituitary adrenal axis suppression 26.84 21.94 7 8409 210 32504900
Hypophosphataemia 25.60 21.94 20 8396 8855 32496255
Aplasia cutis congenita 24.44 21.94 6 8410 140 32504970
Retinal degeneration 24.43 21.94 7 8409 300 32504810
Nephropathy toxic 24.28 21.94 22 8394 11924 32493186
Pneumococcal sepsis 24.19 21.94 9 8407 884 32504226
Mammoplasty 24.03 21.94 4 8412 10 32505100
Hyperbilirubinaemia 23.71 21.94 26 8390 17704 32487406
Jaundice 23.43 21.94 36 8380 34122 32470988
Drug ineffective 23.12 21.94 40 8376 383437 32121673
Renal tubular acidosis 22.98 21.94 11 8405 2021 32503089
Blood insulin increased 22.85 21.94 7 8409 379 32504731
Hepatic cytolysis 22.36 21.94 18 8398 8315 32496795
Liver transplant 22.25 21.94 12 8404 2828 32502282

Pharmacologic Action:

SourceCodeDescription
ATC J05AF02 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Nucleoside and nucleotide reverse transcriptase inhibitors
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:35221 antimetabolite
CHEBI has role CHEBI:36044 anti-virus drug
CHEBI has role CHEBI:53756 reverse transcriptase inhibitor
CHEBI has role CHEBI:63090 purine-nucleoside phosphorylase inhibitors
CHEBI has role CHEBI:176497 anti-aging drugs

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
Metabolic alkalosis contraindication 1388004
Anuria contraindication 2472002 DOID:2983
Hypophosphatemia contraindication 4996001
Hypocalcemia contraindication 5291005
Alcoholism contraindication 7200002
Hypercholesterolemia contraindication 13644009
Hyperkalemia contraindication 14140009
Constipation contraindication 14760008 DOID:2089
Pulmonary edema contraindication 19242006 DOID:11396
Retinal disorder contraindication 29555009 DOID:5679
Sarcoidosis contraindication 31541009 DOID:11335
Dehydration contraindication 34095006
Portal hypertension contraindication 34742003 DOID:10762
Hyperuricemia contraindication 35885006 DOID:1920
Hypertensive disorder contraindication 38341003 DOID:10763
Hypernatremia contraindication 39355002
Fecal impaction contraindication 44635007
Chronic heart failure contraindication 48447003
Acute nephropathy contraindication 58574008
Diarrhea contraindication 62315008
Optic neuritis contraindication 66760008 DOID:1210
Hypercalcemia contraindication 66931009 DOID:12678
Hyperparathyroidism contraindication 66999008 DOID:13543
Hemorrhoids contraindication 70153002 DOID:9746
Diabetes mellitus contraindication 73211009 DOID:9351
Pancreatitis contraindication 75694006 DOID:4989
Oliguria contraindication 83128009
Kidney disease contraindication 90708001 DOID:557
Lactic acidosis contraindication 91273001 DOID:3650
Kidney stone contraindication 95570007
Gastrointestinal obstruction contraindication 126765001
Steatosis of liver contraindication 197321007
Impaired renal function disorder contraindication 197663003
Osteolysis contraindication 203522001
Myocardial dysfunction contraindication 233928007
Disease of liver contraindication 235856003 DOID:409
Chronic diarrhea contraindication 236071009
Aluminum intoxication contraindication 236546003
Peripheral edema contraindication 271809000
Peripheral nerve disease contraindication 302226006
Hypertriglyceridemia contraindication 302870006
Familial hyperkalemic periodic paralysis contraindication 304737009 DOID:14451
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Cardiovascular event risk contraindication 395112001
Breastfeeding (mother) contraindication 413712001
Disorder of coronary artery contraindication 414024009
Obesity contraindication 414916001 DOID:9970
Azotemia contraindication 445009001
Smokes tobacco daily contraindication 449868002
Severe dehydration contraindication 450316000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.94 acidic
pKa2 12.68 acidic
pKa3 1.93 Basic
pKa4 0.76 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
Reverse transcriptase/RNaseH Enzyme INHIBITOR IC50 5.21 WOMBAT-PK CHEMBL

External reference:

IDSource
4020118 VUID
N0000148104 NUI
D00296 KEGG_DRUG
4020118 VANDF
C0012133 UMLSCUI
CHEBI:490877 CHEBI
2DI PDB_CHEM_ID
CHEMBL1460 ChEMBL_ID
DB00900 DRUGBANK_ID
D016049 MESH_DESCRIPTOR_UI
135398739 PUBCHEM_CID
6664 INN_ID
4833 IUPHAR_LIGAND_ID
K3GDH6OH08 UNII
152494 RXNORM
4588 MMSL
63947 MMSL
854 MMSL
d00078 MMSL
003604 NDDF
19194001 SNOMEDCT_US
387105006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Didanosine HUMAN PRESCRIPTION DRUG LABEL 1 53808-0236 CAPSULE, DELAYED RELEASE PELLETS 250 mg ORAL ANDA 27 sections
Didanosine HUMAN PRESCRIPTION DRUG LABEL 1 53808-0353 CAPSULE, DELAYED RELEASE PELLETS 400 mg ORAL ANDA 27 sections
Didanosine HUMAN PRESCRIPTION DRUG LABEL 1 54868-5464 CAPSULE, DELAYED RELEASE PELLETS 250 mg ORAL ANDA 28 sections