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:

PropertyValueReference
S (Water solubility) 0.17 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

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 578.91 31.21 151 2035 36277 63450559
Hypercholesterolaemia 192.50 31.21 57 2129 21277 63465559
Death 172.49 31.21 124 2062 374257 63112579
Hypertriglyceridaemia 159.09 31.21 38 2148 6221 63480615
Hyperlipidaemia 80.96 31.21 29 2157 19542 63467294
Blood triglycerides increased 57.31 31.21 20 2166 12468 63474368
Cognitive disorder 51.80 31.21 29 2157 55786 63431050
Pleural effusion 49.68 31.21 34 2152 93176 63393660
Nervous system disorder 49.38 31.21 20 2166 18746 63468090
Oedema peripheral 48.76 31.21 45 2141 189466 63297370
Oedema 48.26 31.21 34 2152 97588 63389248
Focal segmental glomerulosclerosis 42.95 31.21 10 2176 1458 63485378
Blood cholesterol increased 42.45 31.21 31 2155 94001 63392835
Hallucination, visual 42.12 31.21 18 2168 19280 63467556
Hallucination, auditory 41.94 31.21 16 2170 12808 63474028
Low density lipoprotein increased 40.35 31.21 13 2173 6344 63480492
Pericardial effusion 37.40 31.21 19 2167 30039 63456797
Hallucination 34.01 31.21 22 2164 54795 63432041

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 453.64 33.37 119 1404 23181 34932227
Death 107.77 33.37 107 1416 397942 34557466
Hypercholesterolaemia 101.60 33.37 30 1493 8732 34946676
Hypertriglyceridaemia 44.80 33.37 16 1507 8432 34946976
Oedema peripheral 41.02 33.37 37 1486 119775 34835633
Blood cholesterol increased 34.03 33.37 17 1506 20526 34934882

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 922.31 28.65 246 3192 51436 79689514
Hypercholesterolaemia 264.03 28.65 78 3360 23017 79717933
Death 181.49 28.65 167 3271 566347 79174603
Hypertriglyceridaemia 171.95 28.65 49 3389 12691 79728259
Oedema peripheral 69.85 28.65 69 3369 252219 79488731
Hyperlipidaemia 69.75 28.65 30 3408 26063 79714887
Pleural effusion 60.41 28.65 50 3388 145212 79595738
Hallucination, auditory 59.30 28.65 25 3413 20668 79720282
Oedema 57.89 28.65 45 3393 119535 79621415
Blood cholesterol increased 55.24 28.65 38 3400 83682 79657268
Cognitive disorder 53.98 28.65 35 3403 69891 79671059
Blood triglycerides increased 52.34 28.65 23 3415 21017 79719933
Hallucination, visual 51.26 28.65 26 3412 32703 79708247
Nervous system disorder 49.99 28.65 24 3414 26832 79714118
Hallucination 43.06 28.65 33 3405 85712 79655238
Pericardial effusion 42.85 28.65 26 3412 46211 79694739
Radiation necrosis 40.29 28.65 8 3430 437 79740513
Low density lipoprotein increased 33.60 28.65 13 3425 8609 79732341
Dyslipidaemia 33.14 28.65 14 3424 11619 79729331
Focal segmental glomerulosclerosis 32.62 28.65 10 3428 3311 79737639

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
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
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
Tyrosine-protein kinase JAK2 Kinase Ki 6.28 CHEMBL
Tyrosine-protein kinase FRK Kinase IC50 7.28 CHEMBL
Epidermal growth factor receptor Kinase Ki 7.25 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
10278 INN_ID
7476 IUPHAR_LIGAND_ID
017834 NDDF
782976007 SNOMEDCT_US
782995000 SNOMEDCT_US
4037975 VANDF
2103164 RXNORM
296337 MMSL
35471 MMSL
d09047 MMSL
C000590786 MESH_SUPPLEMENTAL_RECORD_UI

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
Lorbrena HUMAN PRESCRIPTION DRUG LABEL 1 63539-927 TABLET, FILM COATED 25 mg ORAL NDA 31 sections