lorlatinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5302 1454846-35-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • lorlatinib
  • lorbrena
  • PF-06463922
  • PF-6463922
  • lorviqua
Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1 as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors.
  • Molecular weight: 406.42
  • Formula: C21H19FN6O2
  • CLOGP: 2.07
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 1
  • TPSA: 110.06
  • ALOGS: -3.57
  • ROTB: 0
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
June 6, 2019 EMA PFIZER EUROPE MA EEIG
Sept. 21, 2018 FDA PFIZER INC
Sept. 21, 2018 PMDA Pfizer Japan Inc

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
Neoplasm progression 424.86 33.26 109 1368 29048 50574599
Death 164.95 33.26 107 1370 325272 50278375
Hypercholesterolaemia 151.40 33.26 40 1437 11663 50591984
Hypertriglyceridaemia 122.19 33.26 29 1448 5462 50598185
Focal segmental glomerulosclerosis 45.51 33.26 10 1467 1331 50602316
Blood cholesterol increased 39.91 33.26 23 1454 55192 50548455
Oedema 39.77 33.26 25 1452 70156 50533491
Hyperlipidaemia 39.71 33.26 16 1461 17474 50586173
Low density lipoprotein increased 39.67 33.26 12 1465 5634 50598013
Cognitive disorder 39.04 33.26 21 1456 44102 50559545
Pleural effusion 38.76 33.26 26 1451 81428 50522219
Hallucination, auditory 35.81 33.26 13 1464 10715 50592932

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
Neoplasm progression 389.36 45.46 95 880 18517 29555035
Death 98.77 45.46 84 891 342000 29231552
Hypercholesterolaemia 96.55 45.46 26 949 7212 29566340
Hypertriglyceridaemia 46.99 45.46 15 960 7460 29566092

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
Neoplasm progression 710.15 28.44 184 2172 40780 64455596
Hypercholesterolaemia 212.24 28.44 58 2298 15315 64481061
Death 162.52 28.44 136 2220 482569 64013807
Hypertriglyceridaemia 144.03 28.44 40 2316 11165 64485211
Pleural effusion 53.39 28.44 41 2315 126518 64369858
Blood cholesterol increased 53.13 28.44 29 2327 50037 64446339
Oedema peripheral 49.84 28.44 49 2307 210268 64286108
Oedema 43.67 28.44 32 2324 91903 64404473
Hyperlipidaemia 41.18 28.44 19 2337 22957 64473419
Focal segmental glomerulosclerosis 35.45 28.44 10 2346 2934 64493442
Cognitive disorder 35.14 28.44 23 2333 55064 64441312
Nervous system disorder 34.97 28.44 17 2339 23061 64473315
Pericardial effusion 34.21 28.44 20 2336 39234 64457142
Hallucination, auditory 30.32 28.44 14 2342 16925 64479451
Low density lipoprotein increased 29.58 28.44 11 2345 7729 64488647

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01ED05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Anaplastic lymphoma kinase (ALK) inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000187064 Cytochrome P450 2B6 Inducers
FDA MoA N0000190111 Organic Anion Transporter 3 Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA MoA N0000190118 Cytochrome P450 3A Inducers
FDA MoA N0000191264 P-Glycoprotein Inducers
FDA MoA N0000191265 Organic Cation Transporter 1 Inhibitors
FDA MoA N0000191423 Multidrug and Toxin Extrusion Transporter 1 Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:62434 ALK inhibitor

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

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908
ALK fusion gene-positive non-small-cell lung cancer indication 830151004




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.76 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL 10420749 July 27, 2036 TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST
100MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL 10420749 July 27, 2036 TREATMENT OF ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER, PROGRESSED ON: CRIZOTINIB + AT LEAST 1 OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB, OR CERITINIB AS FIRST ALK INHIBITOR FOR METASTATIC DISEASE.
25MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL 10420749 July 27, 2036 TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST
25MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL 10420749 July 27, 2036 TREATMENT OF ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER, PROGRESSED ON: CRIZOTINIB + AT LEAST 1 OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB, OR CERITINIB AS FIRST ALK INHIBITOR FOR METASTATIC DISEASE.

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2023 NEW CHEMICAL ENTITY
25MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2023 NEW CHEMICAL ENTITY
100MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL March 3, 2024 EXPANDED INDICATION OF THE TREATMENT OF ADULT PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST
25MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL March 3, 2024 EXPANDED INDICATION OF THE TREATMENT OF ADULT PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST
100MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON ALECTINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
100MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON CERITINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
100MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON CRIZOTINIB AND AT LEAST ONE OTHER ALK INHIBITOR FOR METASTATIC DIESASE
25MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON ALECTINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
25MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON CERITINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
25MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON CRIZOTINIB AND AT LEAST ONE OTHER ALK INHIBITOR FOR METASTATIC DIESASE
100MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL March 3, 2028 TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST, EXCLUDING PATIENTS WHOSE DISEASE HAS PROGRESSED ON CRIZOTINIB AND AT LEAST ONE OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB OR CERITINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
25MG LORBRENA PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL March 3, 2028 TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST, EXCLUDING PATIENTS WHOSE DISEASE HAS PROGRESSED ON CRIZOTINIB AND AT LEAST ONE OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB OR CERITINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Tyrosine-protein kinase Fes/Fps Kinase INHIBITOR IC50 8.22 SCIENTIFIC LITERATURE DRUG LABEL
ALK tyrosine kinase receptor Kinase INHIBITOR Ki 9.96 SCIENTIFIC LITERATURE DRUG LABEL
Proto-oncogene tyrosine-protein kinase ROS Kinase INHIBITOR IC50 9.30 SCIENTIFIC LITERATURE DRUG LABEL
Focal adhesion kinase 1 Kinase INHIBITOR IC50 7.77 SCIENTIFIC LITERATURE DRUG LABEL
High affinity nerve growth factor receptor Kinase INHIBITOR IC50 7.62 SCIENTIFIC LITERATURE DRUG LABEL
Tyrosine-protein kinase Fer Kinase INHIBITOR IC50 8.48 SCIENTIFIC LITERATURE DRUG LABEL
Activated CDC42 kinase 1 Kinase INHIBITOR IC50 7.77 SCIENTIFIC LITERATURE DRUG LABEL
BDNF/NT-3 growth factors receptor Kinase INHIBITOR IC50 7.64 SCIENTIFIC LITERATURE DRUG LABEL
Protein-tyrosine kinase 2-beta Kinase INHIBITOR IC50 7.85 SCIENTIFIC LITERATURE DRUG LABEL
NT-3 growth factor receptor Kinase INHIBITOR IC50 7.34 SCIENTIFIC LITERATURE DRUG LABEL
Leukocyte tyrosine kinase receptor Kinase INHIBITOR IC50 8.57 SCIENTIFIC LITERATURE DRUG LABEL
Tyrosine-protein kinase FRK Kinase IC50 7.28 CHEMBL

External reference:

IDSource
OSP71S83EU UNII
C4080091 UMLSCUI
CHEBI:143117 CHEBI
53P PDB_CHEM_ID
5P8 PDB_CHEM_ID
QB4 PDB_CHEM_ID
CHEMBL3286830 ChEMBL_ID
71731823 PUBCHEM_CID
DB12130 DRUGBANK_ID
D11012 KEGG_DRUG
7476 IUPHAR_LIGAND_ID
2103164 RXNORM
296337 MMSL
35471 MMSL
d09047 MMSL
782976007 SNOMEDCT_US
782995000 SNOMEDCT_US
4037975 VANDF
017834 NDDF
C000590786 MESH_SUPPLEMENTAL_RECORD_UI
10278 INN_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Lorbrena HUMAN PRESCRIPTION DRUG LABEL 1 0069-0227 TABLET, FILM COATED 25 mg ORAL NDA 32 sections
Lorbrena HUMAN PRESCRIPTION DRUG LABEL 1 0069-0231 TABLET, FILM COATED 100 mg ORAL NDA 32 sections