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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 4318 850140-72-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • afatinib
  • tovok
  • afatinib dimaleate
  • gilotrif
  • BIBW2992
  • afatinib maleate
A quinazoline and butenamide derivative that acts as a tyrosine kinase inhibitor of epidermal growth factor receptors (ERBB RECEPTORS) and is used in the treatment of metastatic NON-SMALL CELL LUNG CANCER.
  • Molecular weight: 485.94
  • Formula: C24H25ClFN5O3
  • CLOGP: 4.34
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 88.61
  • ALOGS: -4.58
  • ROTB: 8
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
40 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Hosey CM, Chan R, Benet LZ
S (Water solubility) 14.36 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.369 Moderate 0.69
caco2-efflux Caco-2 efflux ratio (BA/AB) 11.912 Moderate 0.69
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 8.128 10^-6 cm/s Moderate 0.69
dh-clint Dog hepatocyte intrinsic clearance 4.395 uL/min/10^6 cells Moderate 0.69
dppb Dog plasma protein binding (% unbound) 12.200 % Moderate 0.69
fcs-ppb Fetal calf serum protein binding (% unbound) 26.640 % Moderate 0.69
herg hERG pIC50 5.296 pIC50 Moderate 0.69
hh-clint Human hepatocyte intrinsic clearance 2.377 uL/min/10^6 cells Moderate 0.69
hlm-clint Human liver microsomal intrinsic clearance 13.397 uL/min/mg protein Moderate 0.69
hppb Human plasma protein binding (% unbound) 9.400 % Moderate 0.69
kinase-safety-class ABL1,ABL2,ACVR2B,AKT3,ALK,AURKA,AXL,BLK,BMX,BRAF,BTK,CAMK2B,CAMK2D,CSF1R,CSK,DDR1,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,ERBB4,FGFR1,FLT1,FLT3,FYN,GAK,INSR,IRAK1,ITK,JAK1,KDR,KIT,LCK,LYN,MAP3K1,MAP3K10,MAP3K21,MAP4K2,MAP4K5,MAPK10,MAPK11,MAPK14,MAPK7,MAPKAPK2,MARK4,MET,MKNK1,MKNK2,NTRK1,PAK4,PDK1,PDK2,PDK4,PRKCD,PRKDC,PTK6,RET,RIPK3,SIK2,SIK3,SRC,STK33,SYK,TEK,TTK,YES1 68
kinase-selectivity-class BLK,BRAF,CAMK2D,DDR1,EGFR,EPHB4,ERBB2,ERBB4,FLT3,GAK,IRAK4,KDR,KIT,LCK,LYN,MET,MKNK1,MKNK2,PDK4,SRC,YES1 21
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 32.885 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 29.854 Moderate 0.69
mh-clint Mouse hepatocyte intrinsic clearance 8.453 Moderate 0.69
mppb Mouse plasma protein binding (% unbound) 6 Moderate 0.69
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 40.365 Moderate 0.69
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 13.220 % Moderate 0.69
rat-kpuu-brain Rat brain Kpuu 0.016 % High 1
rh-clint Rat hepatocyte intrinsic clearance 6.166 uL/min/10^6 cells Moderate 0.69
rh-fuinc Rat hepatocyte fraction unbound in incubation 31.970 % Moderate 0.69
rppb Rat plasma protein binding (% unbound) 8.830 % Moderate 0.69
solubility-dd Solubility at pH 7.4 in DMSO 72.611 uM Moderate 0.69

Approvals:

DateAgencyCompanyOrphan
Sept. 25, 2013 EMA
July 12, 2013 FDA BOEHRINGER INGELHEIM

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
Malignant neoplasm progression 2109.37 27.67 674 9007 106196 90512570
Diarrhoea 1345.93 27.67 959 8722 938231 89680535
Paronychia 801.54 27.67 183 9498 7823 90610943
Metastases to central nervous system 377.57 27.67 119 9562 17423 90601343
Dermatitis acneiform 241.59 27.67 67 9614 6287 90612479
Rash 233.92 27.67 350 9331 795750 89823016
Stomatitis 208.92 27.67 197 9484 274501 90344265
Metastases to meninges 196.92 27.67 51 9630 3684 90615082
Dehydration 174.20 27.67 153 9528 194294 90424472
Decreased appetite 173.80 27.67 207 9474 376333 90242433
Skin toxicity 158.36 27.67 49 9632 6730 90612036
EGFR gene mutation 131.22 27.67 24 9657 326 90618440
Drug resistance 115.40 27.67 59 9622 30390 90588376
Acne 107.34 27.67 55 9626 28452 90590314
Pleural effusion 103.90 27.67 90 9591 111901 90506865
Acquired gene mutation 95.06 27.67 23 9658 1256 90617510
Mucosal inflammation 87.52 27.67 62 9619 57563 90561203
Death 86.82 27.67 166 9515 456385 90162381
Dry skin 80.08 27.67 70 9611 88003 90530763
Metastases to bone 75.69 27.67 42 9639 25463 90593303
Disease progression 75.09 27.67 88 9593 156527 90462239
Metastases to liver 70.93 27.67 42 9639 28765 90590001
Therapy partial responder 70.11 27.67 38 9643 22005 90596761
Vomiting 66.02 27.67 209 9472 788084 89830682
Small cell lung cancer 63.68 27.67 18 9663 1806 90616960
Metastases to lung 63.53 27.67 32 9649 15959 90602807
Skin disorder 61.59 27.67 42 9639 36664 90582102
Skin fissures 58.30 27.67 33 9648 20776 90597990
Interstitial lung disease 54.42 27.67 53 9628 76352 90542414
Arthralgia 48.20 27.67 12 9669 778510 89840256
Neoplasm progression 47.91 27.67 39 9642 44447 90574319
Nausea 45.01 27.67 235 9446 1110081 89508685
Epistaxis 44.41 27.67 50 9631 85075 90533691
Pneumonitis 39.90 27.67 35 9646 44135 90574631
Gene mutation 39.83 27.67 13 9668 2117 90616649
Small cell carcinoma 39.71 27.67 8 9673 185 90618581
Onychoclasis 39.07 27.67 18 9663 7381 90611385
Oral pain 38.06 27.67 30 9651 32653 90586113
Non-small cell lung cancer 37.49 27.67 15 9666 4366 90614400
Cutaneous symptom 36.80 27.67 9 9672 514 90618252
Condition aggravated 33.46 27.67 11 9670 595534 90023232
Blood creatinine increased 32.89 27.67 47 9634 101339 90517427
Metastasis 32.62 27.67 15 9666 6122 90612644
Prerenal failure 31.97 27.67 11 9670 2104 90616662
Pain 31.67 27.67 36 9645 996305 89622461
Rash pustular 31.65 27.67 16 9665 8033 90610733
Joint swelling 30.63 27.67 8 9673 503292 90115474
Dysgeusia 29.34 27.67 32 9649 52528 90566238
Hypersensitivity 28.10 27.67 7 9674 454670 90164096

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
Malignant neoplasm progression 1434.69 32.72 518 4546 107882 42508389
Diarrhoea 630.86 32.72 478 4586 460371 42155900
Paronychia 367.30 32.72 88 4976 4167 42612104
Metastases to central nervous system 281.19 32.72 86 4978 10269 42606002
Rash 262.01 32.72 234 4830 276720 42339551
Stomatitis 229.19 32.72 114 4950 50215 42566056
EGFR gene mutation 124.90 32.72 22 5042 212 42616059
Dermatitis acneiform 119.59 32.72 42 5022 7697 42608574
Interstitial lung disease 95.35 32.72 77 4987 78385 42537886
Decreased appetite 86.10 32.72 110 4954 193027 42423244
Skin toxicity 59.13 32.72 24 5040 6525 42609746
Metastases to meninges 56.19 32.72 17 5047 1944 42614327
Metastases to bone 54.10 32.72 29 5035 14780 42601491
Lymphangiosis carcinomatosa 52.40 32.72 14 5050 1023 42615248
Pleural effusion 50.67 32.72 60 5004 97106 42519165
Acne 50.63 32.72 27 5037 13617 42602654
Dehydration 46.84 32.72 70 4994 141697 42474574
Drug resistance 44.48 32.72 35 5029 34213 42582058
Acquired gene mutation 42.29 32.72 13 5051 1567 42614704
Therapy partial responder 41.03 32.72 27 5037 19994 42596277
Disease progression 33.95 32.72 61 5003 143595 42472676
Nail disorder 33.54 32.72 12 5052 2315 42613956

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
Malignant neoplasm progression 3054.74 25.72 1037 12431 173530 110402301
Diarrhoea 1690.87 25.72 1253 12215 1138252 109437579
Paronychia 1043.39 25.72 247 13221 10834 110564997
Metastases to central nervous system 504.43 25.72 163 13305 22654 110553177
Rash 427.35 25.72 510 12958 820454 109755377
Stomatitis 359.00 25.72 282 13186 269960 110305871
Dermatitis acneiform 348.33 25.72 107 13361 12588 110563243
EGFR gene mutation 259.49 25.72 47 13421 523 110575308
Decreased appetite 220.86 25.72 280 13188 475566 110100265
Metastases to meninges 201.03 25.72 57 13411 5071 110570760
Skin toxicity 195.97 25.72 68 13400 11715 110564116
Dehydration 169.92 25.72 189 13279 279322 110296509
Drug resistance 143.58 25.72 88 13380 56286 110519545
Acne 130.33 25.72 69 13399 33451 110542380
Pleural effusion 128.77 25.72 132 13336 177577 110398254
Interstitial lung disease 128.19 25.72 118 13350 139216 110436615
Metastases to bone 120.34 25.72 64 13404 31308 110544523
Acquired gene mutation 118.81 25.72 33 13435 2721 110573110
Therapy partial responder 113.03 25.72 65 13403 36996 110538835
Metastases to liver 97.20 25.72 58 13410 35328 110540503
Small cell lung cancer 91.49 25.72 28 13440 3244 110572587
Lymphangiosis carcinomatosa 81.31 25.72 24 13444 2458 110573373
Dry skin 79.79 25.72 81 13387 107572 110468259
Mucosal inflammation 78.02 25.72 76 13392 96065 110479766
Disease progression 74.72 25.72 118 13350 243916 110331915
Metastases to lung 74.47 25.72 42 13426 23021 110552810
Death 66.27 25.72 211 13257 698658 109877173
Gene mutation 65.65 25.72 22 13446 3407 110572424
Vomiting 64.01 25.72 249 13219 910426 109665405
Skin fissures 56.73 25.72 36 13432 24422 110551409
Skin disorder 52.90 25.72 43 13425 42870 110532961
Rash pustular 51.53 25.72 27 13441 12802 110563029
Arthralgia 48.93 25.72 17 13451 779615 109796216
Nausea 46.88 25.72 283 13185 1235407 109340424
Neoplasm progression 46.74 25.72 48 13420 64547 110511284
Cutaneous symptom 44.66 25.72 12 13456 873 110574958
Small cell carcinoma 44.43 25.72 10 13458 347 110575484
Epistaxis 41.18 25.72 64 13404 130308 110445523
Malignant neoplasm of pleura 38.46 25.72 8 13460 190 110575641
Condition aggravated 38.22 25.72 21 13447 734815 109841016
Gastrointestinal toxicity 37.89 25.72 21 13447 11127 110564704
Pneumonitis 36.81 25.72 46 13422 76485 110499346
Metastasis 34.92 25.72 18 13450 8249 110567582
Metastases to pleura 34.65 25.72 12 13456 2051 110573780
Onychoclasis 34.20 25.72 17 13451 7220 110568611
Lung adenocarcinoma 32.52 25.72 18 13450 9513 110566318
Pain 31.73 25.72 42 13426 954913 109620918
Nail disorder 31.40 25.72 37 13431 57898 110517933
Hypertension 30.48 25.72 12 13456 510072 110065759
Dysgeusia 30.40 25.72 40 13428 69945 110505886
Cheilitis 30.22 25.72 15 13453 6350 110569481
Metastases to spine 29.62 25.72 14 13454 5329 110570502
Blood creatinine increased 29.14 25.72 67 13401 182822 110393009
Prerenal failure 28.83 25.72 13 13455 4446 110571385
Hypersensitivity 28.62 25.72 7 13461 403991 110171840
Product dose omission issue 28.53 25.72 3 13465 321779 110254052
Nail bed infection 27.60 25.72 6 13462 177 110575654
Product use issue 27.39 25.72 3 13465 311692 110264139
Malignant pleural effusion 26.68 25.72 12 13456 4081 110571750
Malignant transformation 26.12 25.72 9 13459 1516 110574315

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EB03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
FDA MoA N0000175076 Protein Kinase Inhibitors
MeSH PA D000092004 Tyrosine Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:38637 tyrosine kinase inhibitor

Related Drugs by ATC class:

L01EB Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors 8 drugs
dacomitiniberlotinibgefitinibicotiniblazertinibmobocertinibolmutinibosimertinib

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

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer, positive for epidermal growth factor receptor expression indication 426964009




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.1 acidic
pKa2 8.94 Basic
pKa3 4.09 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 20MG BASE GILOTRIF BOEHRINGER INGELHEIM N201292 July 12, 2013 RX TABLET ORAL 9539258 Nov. 9, 2026 TREATMENT OF PATIENTS WITH ADVANCED (METASTATIC) NON-SMALL CELL LUNG CANCER WHOSE DISEASE PROGRESSED DURING OR AFTER PLATINUM-BASED CHEMOTHERAPY
EQ 30MG BASE GILOTRIF BOEHRINGER INGELHEIM N201292 July 12, 2013 RX TABLET ORAL 9539258 Nov. 9, 2026 TREATMENT OF PATIENTS WITH ADVANCED (METASTATIC) NON-SMALL CELL LUNG CANCER WHOSE DISEASE PROGRESSED DURING OR AFTER PLATINUM-BASED CHEMOTHERAPY
EQ 40MG BASE GILOTRIF BOEHRINGER INGELHEIM N201292 July 12, 2013 RX TABLET ORAL 9539258 Nov. 9, 2026 TREATMENT OF PATIENTS WITH ADVANCED (METASTATIC) NON-SMALL CELL LUNG CANCER WHOSE DISEASE PROGRESSED DURING OR AFTER PLATINUM-BASED CHEMOTHERAPY

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR Kd 8.20 CHEMBL CHEMBL
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR Kd 8.30 CHEMBL CHEMBL
Epidermal growth factor receptor Kinase INHIBITOR Kd 10 CHEMBL CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase Kd 5.55 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 6.24 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 5.85 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase IC50 5.44 CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform Kinase Kd 6.33 CHEMBL
Myosin light chain kinase, smooth muscle Kinase Kd 4.50 CHEMBL
Tyrosine-protein kinase HCK Kinase Kd 5.66 CHEMBL
Mitogen-activated protein kinase 10 Kinase Kd 5.70 CHEMBL
Hepatocyte growth factor receptor Kinase Kd 5.66 CHEMBL
Tyrosine-protein kinase Lyn Kinase IC50 6.13 CHEMBL
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform Kinase Kd 5.89 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 5.37 CHEMBL
Mitogen-activated protein kinase 11 Kinase Kd 5.55 CHEMBL
Serine/threonine-protein kinase 17A Kinase Kd 5.64 CHEMBL
Ephrin type-A receptor 6 Kinase Kd 6.47 CHEMBL
Casein kinase I isoform epsilon Kinase Kd 5.89 CHEMBL
Mitogen-activated protein kinase 14 Kinase Kd 5.89 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 5.85 CHEMBL
Cyclin-G-associated kinase Kinase Kd 7.10 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 5.57 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 5.43 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2 Kinase Kd 5.80 CHEMBL
Mitogen-activated protein kinase 9 Kinase Kd 5.68 CHEMBL
MAP kinase-activated protein kinase 2 Kinase Kd 6.09 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 5.28 CHEMBL
Ribosomal protein S6 kinase alpha-6 Kinase Kd 5.51 CHEMBL
Tyrosine-protein kinase TXK Kinase Kd 5.51 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 1B Kinase Kd 5.55 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 1 Kinase Kd 5.74 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 6.66 CHEMBL
Citron Rho-interacting kinase Kinase Kd 5.54 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 1A Kinase Kd 6.01 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 2 Kinase Kd 5.74 CHEMBL
Ephrin type-B receptor 6 Kinase Kd 5.51 CHEMBL
Homeodomain-interacting protein kinase 4 Kinase Kd 6.44 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 6.62 CHEMBL
Receptor tyrosine-protein kinase erbB-3 Kinase Kd 5.35 CHEMBL
Serine/threonine-protein kinase SBK1 Kinase Kd 5.32 CHEMBL
Macrophage-stimulating protein receptor Kinase IC50 5.27 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 5.89 CHEMBL
Adenosine kinase Kinase Kd 5.46 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 6.64 CHEMBL

External reference:

IDSource
4032662 VUID
N0000188388 NUI
D09724 KEGG_DRUG
4032662 VANDF
4032663 VANDF
C2987648 UMLSCUI
CHEBI:61390 CHEBI
0WM PDB_CHEM_ID
CHEMBL1173655 ChEMBL_ID
CHEMBL2105712 ChEMBL_ID
D000077716 MESH_DESCRIPTOR_UI
DB08916 DRUGBANK_ID
5667 IUPHAR_LIGAND_ID
9230 INN_ID
850140-73-7 SECONDARY_CAS_RN
41UD74L59M UNII
10184653 PUBCHEM_CID
1430268 RXNORM
204142 MMSL
29566 MMSL
d08113 MMSL
015117 NDDF
015118 NDDF
703579002 SNOMEDCT_US
703580004 SNOMEDCT_US
703582007 SNOMEDCT_US
41UD74L59M INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Gilotrif HUMAN PRESCRIPTION DRUG LABEL 1 0597-0137 TABLET, FILM COATED 30 mg ORAL NDA 30 sections
Gilotrif HUMAN PRESCRIPTION DRUG LABEL 1 0597-0138 TABLET, FILM COATED 40 mg ORAL NDA 30 sections
Gilotrif HUMAN PRESCRIPTION DRUG LABEL 1 0597-0141 TABLET, FILM COATED 20 mg ORAL NDA 30 sections