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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5062 1421373-65-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • osimertinib
  • tagrisso
  • AZD9291
  • AZD-9291
  • AZD 9291
  • osimertinib mesylate
  • osimertinib mesilate
  • AZD9291 mesylate
  • mereletinib
Osimertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) at approximately 9-fold lower concentrations than wild-type. In cultured cells and animal tumor implantation models, osimertinib exhibited anti-tumor activity against NSCLC lines harboring EGFR-mutations (T790M/L858R, L858R, T790M/exon 19 deletion, and exon 19 deletion) and, to a lesser extent, wild-type EGFR amplifications.
  • Molecular weight: 499.62
  • Formula: C28H33N7O2
  • CLOGP: 4.60
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 2
  • TPSA: 87.55
  • ALOGS: -4.35
  • ROTB: 10

  • Status: ONP

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

Drug dosage:

DoseUnitRoute
80 mg O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
March 28, 2016 PMDA AstraZeneca K.K.
Feb. 2, 2016 EMA AstraZeneca AB
Nov. 13, 2015 FDA ASTRAZENECA PHARMS

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 1331.55 25.22 459 6833 71082 53270692
Drug resistance 625.65 25.22 191 7101 19771 53322003
Acquired gene mutation 571.85 25.22 98 7194 679 53341095
Death 460.43 25.22 382 6910 356850 52984924
Interstitial lung disease 421.84 25.22 190 7102 58432 53283342
Metastases to central nervous system 252.29 25.22 85 7207 11972 53329802
Paronychia 218.62 25.22 62 7230 4922 53336852
EGFR gene mutation 208.72 25.22 35 7257 208 53341566
Myelosuppression 146.91 25.22 58 7234 12770 53329004
Malignant transformation 137.40 25.22 26 7266 330 53341444
Hepatic function abnormal 127.44 25.22 73 7219 36826 53304948
Metastases to meninges 123.33 25.22 33 7259 2106 53339668
Pneumonitis 122.71 25.22 67 7225 30821 53310953
Pleural effusion 111.22 25.22 94 7198 88485 53253289
Lung disorder 95.64 25.22 67 7225 47812 53293962
Electrocardiogram QT prolonged 83.66 25.22 66 7226 56337 53285437
Dermatitis acneiform 83.61 25.22 29 7263 4441 53337333
Platelet count decreased 82.38 25.22 87 7205 108012 53233762
Decreased appetite 81.65 25.22 122 7170 214852 53126922
Metastases to bone 79.71 25.22 43 7249 19285 53322489
Diarrhoea 74.68 25.22 220 7072 625326 52716448
Lymphangiosis carcinomatosa 70.62 25.22 19 7273 1237 53340537
Cardiac failure 68.79 25.22 71 7221 85773 53256001
Disease progression 65.44 25.22 75 7217 101845 53239929
Metastases to liver 59.74 25.22 37 7255 21459 53320315
Metastases to lung 53.79 25.22 28 7264 11676 53330098
Erythema multiforme 51.15 25.22 26 7266 10323 53331451
Pulmonary embolism 50.74 25.22 70 7222 114372 53227402
Radiation pneumonitis 46.91 25.22 14 7278 1326 53340448
Pain 45.92 25.22 12 7280 588386 52753388
Metastasis 39.24 25.22 17 7275 4714 53337060
Liver disorder 39.16 25.22 37 7255 40118 53301656
Gene mutation 38.89 25.22 12 7280 1271 53340503
Multiple-drug resistance 38.32 25.22 15 7277 3220 53338554
Taste disorder 36.43 25.22 19 7273 7949 53333825
Off label use 34.13 25.22 141 7151 472071 52869703
Neutrophil count decreased 32.94 25.22 37 7255 49061 53292713
Arthralgia 32.35 25.22 10 7282 439773 52902001
Small cell lung cancer 32.04 25.22 11 7281 1632 53340142
Ejection fraction decreased 31.07 25.22 24 7268 19824 53321950
Drug ineffective 30.98 25.22 40 7252 817205 52524569
Malignant pleural effusion 30.70 25.22 12 7280 2565 53339209
Dry skin 29.87 25.22 34 7258 45726 53296048
Thrombocytopenia 29.36 25.22 61 7231 138666 53203108
Carcinoembryonic antigen increased 28.72 25.22 10 7282 1547 53340227
Deep vein thrombosis 28.46 25.22 45 7247 82868 53258906
Cardiomyopathy 27.48 25.22 21 7271 17067 53324707
Rash 27.45 25.22 127 7165 446064 52895710
Pulmonary alveolar haemorrhage 27.43 25.22 13 7279 4437 53337337
Respiratory failure 27.13 25.22 49 7243 100463 53241311
Blood creatine phosphokinase increased 26.91 25.22 26 7266 28959 53312815
Stomatitis 26.69 25.22 48 7244 98110 53243664
Metastases to lymph nodes 26.40 25.22 15 7277 7425 53334349

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 721.03 30.59 281 3244 78215 32431786
Drug resistance 405.05 30.59 134 3391 22831 32487170
Acquired gene mutation 343.34 30.59 66 3459 1181 32508820
Interstitial lung disease 229.06 30.59 120 3405 64881 32445120
Death 172.93 30.59 208 3317 382309 32127692
EGFR gene mutation 171.50 30.59 26 3499 95 32509906
Metastases to central nervous system 168.16 30.59 53 3472 7655 32502346
Pneumonitis 109.65 30.59 57 3468 30077 32479924
Metastases to meninges 104.34 30.59 25 3500 1293 32508708
Paronychia 82.09 30.59 25 3500 3212 32506789
Hepatic function abnormal 62.48 30.59 46 3479 44794 32465207
Metastases to bone 52.98 30.59 25 3500 10685 32499316
Lung disorder 52.42 30.59 37 3488 33717 32476284
Malignant transformation 51.87 30.59 13 3512 810 32509191
Radiation pneumonitis 42.13 30.59 14 3511 2378 32507623
Lymphangiosis carcinomatosa 40.51 30.59 11 3514 938 32509063
Metastases to lung 39.64 30.59 19 3506 8398 32501603
Myelosuppression 39.31 30.59 21 3504 11655 32498346
Dermatitis acneiform 39.04 30.59 17 3508 6028 32503973
Liver disorder 36.42 30.59 29 3496 31625 32478376
Pulmonary embolism 33.15 30.59 43 3482 83616 32426385

Pharmacologic Action:

SourceCodeDescription
ATC L01EB04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
FDA MoA N0000191266 Cytochrome P450 1A2 Inducers
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:74440 EGFR inhibitor

Drug Use (View source of the data)

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

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.64 acidic
pKa2 7.93 Basic
pKa3 5.6 Basic
pKa4 1.32 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 9732058 July 25, 2032 ADJUVANT THERAPY AFTER TUMOR RESECTION IN PATIENTS WITH NON-SMALL CELL LUNG CANCER(NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19DELETIONS OR EXON 21 L858R MUTATIONS
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 9732058 July 25, 2032 TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 9732058 July 25, 2032 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21L858R MUTATIONS
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 9732058 July 25, 2032 ADJUVANT THERAPY AFTER TUMOR RESECTION IN PATIENTS WITH NON-SMALL CELL LUNG CANCER(NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19DELETIONS OR EXON 21 L858R MUTATIONS
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 9732058 July 25, 2032 TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 9732058 July 25, 2032 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21L858R MUTATIONS
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 8946235 Aug. 8, 2032 ADJUVANT THERAPY AFTER TUMOR RESECTION IN PATIENTS WITH NON-SMALL CELL LUNG CANCER(NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19DELETIONS OR EXON 21 L858R MUTATIONS
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 8946235 Aug. 8, 2032 TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 8946235 Aug. 8, 2032 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21L858R MUTATIONS
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 8946235 Aug. 8, 2032 ADJUVANT THERAPY AFTER TUMOR RESECTION IN PATIENTS WITH NON-SMALL CELL LUNG CANCER(NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19DELETIONS OR EXON 21 L858R MUTATIONS
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 8946235 Aug. 8, 2032 TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 8946235 Aug. 8, 2032 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21L858R MUTATIONS
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 10183020 Jan. 2, 2035 ADJUVANT THERAPY AFTER TUMOR RESECTION IN PATIENTS WITH NON-SMALL CELL LUNG CANCER(NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19DELETIONS OR EXON 21 L858R MUTATIONS
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 10183020 Jan. 2, 2035 TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 10183020 Jan. 2, 2035 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21L858R MUTATIONS
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 10183020 Jan. 2, 2035 ADJUVANT THERAPY AFTER TUMOR RESECTION IN PATIENTS WITH NON-SMALL CELL LUNG CANCER(NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19DELETIONS OR EXON 21 L858R MUTATIONS
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 10183020 Jan. 2, 2035 TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL 10183020 Jan. 2, 2035 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21L858R MUTATIONS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Nov. 13, 2022 FOR TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), AS DETECTED BY AN FDA-APPROVED TEST, WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Nov. 13, 2022 FOR TREATMENT OF PATIENTS WITH METASTATIC EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) T790M MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC), AS DETECTED BY AN FDA-APPROVED TEST, WHO HAVE PROGRESSED ON OR AFTER EGFR TKI THERAPY
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Dec. 18, 2023 INDICATION OF OSIMERTINIB AS ADJUVANT THERAPY AFTER TUMOR RESECTION IN ADULT PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Dec. 18, 2023 INDICATION OF OSIMERTINIB AS ADJUVANT THERAPY AFTER TUMOR RESECTION IN ADULT PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL April 18, 2025 INDICATED FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL April 18, 2025 INDICATED FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 40MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Dec. 18, 2027 FOR ADJUVANT THERAPY AFTER TUMOR RESECTION IN ADULT PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST
EQ 80MG BASE TAGRISSO ASTRAZENECA N208065 Nov. 13, 2015 RX TABLET ORAL Dec. 18, 2027 FOR ADJUVANT THERAPY AFTER TUMOR RESECTION IN ADULT PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Epidermal growth factor receptor Kinase INHIBITOR IC50 7.82 SCIENTIFIC LITERATURE DRUG LABEL
Ribosyldihydronicotinamide dehydrogenase [quinone] Enzyme Kd 5.44 CHEMBL
Insulin receptor Kinase IC50 6.04 CHEMBL
ALK tyrosine kinase receptor Kinase IC50 6.75 CHEMBL
Tyrosine-protein kinase BTK Kinase Kd 6.28 CHEMBL
Tyrosine-protein kinase Tec Kinase Kd 6.49 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.79 CHEMBL
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma Kinase Kd 5.53 CHEMBL
Dipeptidyl peptidase 1 Enzyme IC50 4.48 CHEMBL
Cysteine--tRNA ligase, cytoplasmic Enzyme Kd 7.92 CHEMBL
Receptor tyrosine-protein kinase erbB-3 Kinase IC50 8.68 CHEMBL
Epidermal growth factor receptor Kinase IC50 7.09 CHEMBL

External reference:

IDSource
3C06JJ0Z2O UNII
1421373-66-1 SECONDARY_CAS_RN
4035124 VANDF
C4058811 UMLSCUI
CHEBI:90943 CHEBI
YY3 PDB_CHEM_ID
CHEMBL3353410 ChEMBL_ID
71496458 PUBCHEM_CID
DB09330 DRUGBANK_ID
CHEMBL3545063 ChEMBL_ID
C000596361 MESH_SUPPLEMENTAL_RECORD_UI
7719 IUPHAR_LIGAND_ID
10043 INN_ID
1721559 RXNORM
237132 MMSL
31292 MMSL
d08397 MMSL
016583 NDDF
016584 NDDF
716032009 SNOMEDCT_US
734660003 SNOMEDCT_US
781312009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TAGRISSO HUMAN PRESCRIPTION DRUG LABEL 1 0310-1349 TABLET, FILM COATED 40 mg ORAL NDA 27 sections
TAGRISSO HUMAN PRESCRIPTION DRUG LABEL 1 0310-1350 TABLET, FILM COATED 80 mg ORAL NDA 27 sections