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 473.07 32.22 122 1585 31894 56258466
Hypercholesterolaemia 178.46 32.22 48 1659 14425 56275935
Death 175.53 32.22 115 1592 341311 55949049
Hypertriglyceridaemia 156.03 32.22 36 1671 5780 56284580
Hyperlipidaemia 56.20 32.22 21 1686 18088 56272272
Pleural effusion 46.28 32.22 30 1677 85450 56204910
Focal segmental glomerulosclerosis 44.23 32.22 10 1697 1456 56288904
Blood cholesterol increased 43.07 32.22 27 1680 72552 56217808
Low density lipoprotein increased 43.00 32.22 13 1694 5861 56284499
Cognitive disorder 41.57 32.22 23 1684 49110 56241250
Hallucination, auditory 38.07 32.22 14 1693 11510 56278850
Oedema 37.70 32.22 26 1681 81894 56208466
Blood triglycerides increased 34.24 32.22 13 1694 11664 56278696
Nervous system disorder 32.88 32.22 14 1693 16875 56273485
Hallucination, visual 32.43 32.22 14 1693 17454 56272906
Pericardial effusion 32.35 32.22 16 1691 27159 56263201

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 424.43 40.02 105 1015 20167 31676057
Death 115.93 40.02 97 1023 360472 31335752
Hypercholesterolaemia 96.61 40.02 27 1093 8003 31688221
Hypertriglyceridaemia 45.33 40.02 15 1105 7783 31688441
Oedema peripheral 41.90 40.02 33 1087 109806 31586418

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 786.70 28.03 205 2466 45023 70880750
Hypercholesterolaemia 246.47 28.03 68 2603 18049 70907724
Death 182.90 28.03 151 2520 509910 70415863
Hypertriglyceridaemia 172.89 28.03 47 2624 11764 70914009
Pleural effusion 59.15 28.03 45 2626 132819 70792954
Blood cholesterol increased 55.65 28.03 33 2638 64571 70861202
Oedema peripheral 54.26 28.03 54 2617 228037 70697736
Hyperlipidaemia 49.34 28.03 22 2649 23841 70901932
Nervous system disorder 42.79 28.03 20 2651 24126 70901647
Cognitive disorder 41.96 28.03 27 2644 60929 70864844
Oedema 41.53 28.03 33 2638 103548 70822225
Hallucination, auditory 38.21 28.03 17 2654 18311 70907462
Pericardial effusion 37.69 28.03 22 2649 41754 70884019
Radiation necrosis 35.95 28.03 7 2664 397 70925376
Focal segmental glomerulosclerosis 34.31 28.03 10 2661 3194 70922579
Blood triglycerides increased 33.95 28.03 16 2655 19648 70906125
Low density lipoprotein increased 32.45 28.03 12 2659 8053 70917720
Hallucination, visual 30.62 28.03 17 2654 29320 70896453
Hallucination 29.91 28.03 24 2647 76236 70849537

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
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
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
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
10278 INN_ID
7476 IUPHAR_LIGAND_ID
296337 MMSL
35471 MMSL
d09047 MMSL
017834 NDDF
782976007 SNOMEDCT_US
782995000 SNOMEDCT_US
4037975 VANDF
C000590786 MESH_SUPPLEMENTAL_RECORD_UI
2103164 RXNORM

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