larotrectinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| tyrosine kinase inhibitors | 5305 | 1223403-58-4 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Larotrectinib is an inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC50 values between 5-11 nM. One other kinase TNK2 was inhibited at approximately 100-fold higher concentration. TRKA, B, and C are encoded by the genes NTRK1, NTRK2, and NTRK3.Chromosomal rearrangements involving in-frame fusions of these genes with various partners can result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 0.20 | g | O |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| S (Water solubility) | 1 mg/mL | Bocci G, Oprea TI, Benet LZ |
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 1 | Bocci G, Oprea TI, Benet LZ |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Sept. 19, 2019 | EMA | Bayer AG | |
| Nov. 26, 2018 | FDA | LOXO ONCOLOGY INC | |
| March 23, 2021 | PMDA | Bayer Yakuhin, Ltd. |
FDA Adverse Event Reporting System (Female)
None
FDA Adverse Event Reporting System (Male)
None
FDA Adverse Event Reporting System (Geriatric)
None
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | L01EX12 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Other protein kinase inhibitors |
| FDA EPC | N0000175605 | Kinase Inhibitor |
| FDA MoA | N0000193859 | Tropomyosin Receptor Kinases Inhibitors |
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Malignant Neoplasm | indication | 367651003 | |
| NTRK fusion gene-positive advanced or recurrent solid tumors | indication | 786710002 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 8.36 | acidic |
| pKa2 | 3.52 | Basic |
Orange Book patent data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Patent number | Patent expiration date | Patent use |
|---|---|---|---|---|---|---|---|---|---|---|
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10005783 | Oct. 21, 2029 | METHOD OF TREATING NEUROBLASTOMA, GLIOMA, THYROID, AND BREAST CANCER SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10047097 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION AFTER SURGICAL RESECTION |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10774085 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 8865698 | Oct. 21, 2029 | METHOD OF TREATING CANCEROUS SOLID TUMORS |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 9447104 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 9676783 | Oct. 21, 2029 | METHOD OF TREATING CANCEROUS SOLID TUMORS |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10005783 | Oct. 21, 2029 | METHOD OF TREATING NEUROBLASTOMA, GLIOMA, THYROID, AND BREAST CANCER SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10047097 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION AFTER SURGICAL RESECTION |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10774085 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 8865698 | Oct. 21, 2029 | METHOD OF TREATING CANCEROUS SOLID TUMORS |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 9447104 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 9676783 | Oct. 21, 2029 | METHOD OF TREATING CANCEROUS SOLID TUMORS |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 10005783 | Oct. 21, 2029 | METHOD OF TREATING NEUROBLASTOMA, GLIOMA, THYROID, AND BREAST CANCER SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 10047097 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION AFTER SURGICAL RESECTION |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 10774085 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 8865698 | Oct. 21, 2029 | METHOD OF TREATING CANCEROUS SOLID TUMORS |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 9447104 | Oct. 21, 2029 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 9676783 | Oct. 21, 2029 | METHOD OF TREATING CANCEROUS SOLID TUMORS |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10285993 | Nov. 16, 2035 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10813936 | Nov. 16, 2035 | METHOD OF TREATING LUNG CANCER, UNDIFFERENTIATED SARCOMA, OR COLORECTAL CANCER THAT EXHIBITS AN NTRK GENE FUSION |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 9782414 | Nov. 16, 2035 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION IN A PEDIATRIC PATIENT |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10285993 | Nov. 16, 2035 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 10813936 | Nov. 16, 2035 | METHOD OF TREATING LUNG CANCER, UNDIFFERENTIATED SARCOMA, OR COLORECTAL CANCER THAT EXHIBITS AN NTRK GENE FUSION |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | 9782414 | Nov. 16, 2035 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION IN A PEDIATRIC PATIENT |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 9782414 | Nov. 16, 2035 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK FUSION GENE IN A PEDIATRIC PATIENT |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 10045991 | April 4, 2037 | METHOD OF TREATING CMN, IFS, HGG, DIPGS, PTC, SOFT TISSUE SARCOMA, AND SPINDLE CELL SARCOMA SOLID TUMORS EXHIBITING AN NTRK GENE FUSION IN A PEDIATRIC PATIENT WITH AN ORAL SOLUTION |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 11191766 | April 4, 2037 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK FUSION GENE IN A PEDIATRIC PATIENT |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | 11484535 | April 4, 2037 | METHOD OF TREATING SOLID TUMORS THAT EXHIBIT AN NTRK GENE FUSION |
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | Nov. 26, 2023 | NEW CHEMICAL ENTITY |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | Nov. 26, 2023 | NEW CHEMICAL ENTITY |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | Nov. 26, 2023 | NEW CHEMICAL ENTITY |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT ARE METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC RECEPTOR TYROSINE KINASE (NTRK) GENE FUSION WITHOUT A KNOWN ACQUIRED RESISTANCE MUTATION |
| EQ 100MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT HAVE NO SATISFACTORY ALTERNATIVE TREATMENTS OR THAT HAVE PROGRESSED FOLLOWING TREATMENT |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT ARE METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC RECEPTOR TYROSINE KINASE (NTRK) GENE FUSION WITHOUT A KNOWN ACQUIRED RESISTANCE MUTATION |
| EQ 25MG BASE | VITRAKVI | BAYER HLTHCARE | N210861 | Nov. 26, 2018 | RX | CAPSULE | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT HAVE NO SATISFACTORY ALTERNATIVE TREATMENTS OR THAT HAVE PROGRESSED FOLLOWING TREATMENT |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT ARE METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC RECEPTOR TYROSINE KINASE (NTRK) GENE FUSION WITHOUT A KNOWN ACQUIRED RESISTANCE MUTATION |
| EQ 20MG BASE/ML | VITRAKVI | BAYER HEALTHCARE | N211710 | Nov. 26, 2018 | RX | SOLUTION | ORAL | Nov. 26, 2025 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT HAVE NO SATISFACTORY ALTERNATIVE TREATMENTS OR THAT HAVE PROGRESSED FOLLOWING TREATMENT |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| High affinity nerve growth factor receptor | Kinase | INHIBITOR | IC50 | 8.19 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| BDNF/NT-3 growth factors receptor | Kinase | INHIBITOR | IC50 | 8.09 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| NT-3 growth factor receptor | Kinase | INHIBITOR | IC50 | 7.98 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| Activated CDC42 kinase 1 | Kinase | IC50 | 6.24 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| PF9462I9HX | UNII |
| C4524315 | UMLSCUI |
| CHEMBL3889654 | ChEMBL_ID |
| 46188928 | PUBCHEM_CID |
| DB14723 | DRUGBANK_ID |
| CHEMBL3989939 | ChEMBL_ID |
| D11137 | KEGG_DRUG |
| 10360 | INN_ID |
| 8909 | IUPHAR_LIGAND_ID |
| 1223405-08-0 | SECONDARY_CAS_RN |
| 017848 | NDDF |
| 017849 | NDDF |
| 1217200005 | SNOMEDCT_US |
| 782977003 | SNOMEDCT_US |
| 782991009 | SNOMEDCT_US |
| 4038034 | VANDF |
| 2104548 | RXNORM |
| 299174 | MMSL |
| 35642 | MMSL |
| d09074 | MMSL |
| C000609083 | MESH_SUPPLEMENTAL_RECORD_UI |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50419-390 | CAPSULE | 25 mg | ORAL | NDA | 28 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50419-390 | CAPSULE | 25 mg | ORAL | NDA | 28 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50419-391 | CAPSULE | 100 mg | ORAL | NDA | 28 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50419-391 | CAPSULE | 100 mg | ORAL | NDA | 28 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50419-392 | SOLUTION, CONCENTRATE | 20 mg | OROPHARYNGEAL | NDA | 28 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50419-392 | SOLUTION, CONCENTRATE | 20 mg | OROPHARYNGEAL | NDA | 28 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50419-393 | SOLUTION, CONCENTRATE | 20 mg | OROPHARYNGEAL | NDA | 28 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 71777-390 | CAPSULE | 25 mg | ORAL | NDA | 27 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 71777-391 | CAPSULE | 100 mg | ORAL | NDA | 27 sections |
| VITRAKVI | HUMAN PRESCRIPTION DRUG LABEL | 1 | 71777-392 | SOLUTION | 20 mg | ORAL | NDA | 27 sections |