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

Stem definition	Drug id	CAS RN
humanized origin	5367	1826843-81-5

Description:

Molecule	Description
Synonyms: trastuzumab deruxtecan enhertu DS-8201a fam-trastuzumab deruxtecan-nxki	Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker. Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death. Molecular weight: Formula: CLOGP: LIPINSKI: None HAC: None HDO: None TPSA: ALOGS: ROTB: None

Molecule

Description

Synonyms:

trastuzumab deruxtecan
enhertu
DS-8201a
fam-trastuzumab deruxtecan-nxki

Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker. Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death.

Molecular weight:
Formula:
CLOGP:
LIPINSKI: None
HAC: None
HDO: None
TPSA:
ALOGS:
ROTB: None

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company
Jan. 18, 2021	EMA	DAIICHI SANKYO EUROPE GmbH
Dec. 20, 2019	FDA	DAIICHI SANKYO
March 25, 2020	PMDA	Daiichi Sankyo Company, Limited

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Interstitial lung disease	800.51	37.81	260	4460	61648	63422654
Disease progression	549.62	37.81	237	4483	122521	63361781
Pneumonitis	297.51	37.81	108	4612	35114	63449188
Death	219.45	37.81	197	4523	374184	63110118
Nausea	184.40	37.81	267	4453	854204	62630098
No adverse event	115.69	37.81	58	4662	41347	63442955
Off label use	107.29	37.81	184	4536	674278	62810024
Neutrophil count decreased	98.86	37.81	58	4662	56348	63427954
Metastases to central nervous system	80.81	37.81	32	4688	13073	63471229
Ejection fraction decreased	70.43	37.81	34	4686	22298	63462004
Underdose	66.62	37.81	35	4685	27421	63456881
Malignant neoplasm progression	59.35	37.81	49	4671	82072	63402230
Pulmonary toxicity	57.98	37.81	23	4697	9432	63474870
Ascites	56.27	37.81	36	4684	40692	63443610
Lung opacity	51.76	37.81	16	4704	3152	63481150
Neutropenia	46.51	37.81	61	4659	174944	63309358
Vomiting	46.19	37.81	117	4603	559500	62924802
Pneumocystis jirovecii pneumonia	42.27	37.81	22	4698	16892	63467410
Excessive eye blinking	41.36	37.81	11	4709	1269	63483033

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	322.96	65.72	121	963	107956	34847891
Underdose	98.38	65.72	30	1054	13750	34942097
Off label use	91.98	65.72	86	998	419438	34536409
Decreased appetite	86.35	65.72	57	1027	166335	34789512
Neutrophil count decreased	81.74	65.72	37	1047	51067	34904780
Interstitial lung disease	79.04	65.72	39	1045	65243	34890604

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	697.39	35.39	280	3666	184082	79556360
Interstitial lung disease	402.90	35.39	165	3781	112435	79628007
Neutrophil count decreased	188.25	35.39	92	3854	93867	79646575
Pneumonitis	173.04	35.39	76	3870	60784	79679658
Underdose	168.96	35.39	63	3883	33088	79707354
Decreased appetite	86.50	35.39	95	3851	342323	79398119
Ascites	83.67	35.39	50	3896	75512	79664930
Nausea	81.29	35.39	158	3788	957038	78783404
Death	80.68	35.39	118	3828	566396	79174046
Off label use	71.20	35.39	145	3801	907070	78833372
Febrile neutropenia	68.72	35.39	70	3876	230929	79509513
Platelet count decreased	63.43	35.39	62	3884	194602	79545840
Metastases to central nervous system	58.20	35.39	24	3922	16351	79724091
Myelosuppression	53.43	35.39	30	3916	40266	79700176
Pulmonary toxicity	49.56	35.39	20	3926	12894	79727548
Anaemia	48.29	35.39	82	3864	444933	79295509
KL-6 increased	47.31	35.39	8	3938	153	79740289
No adverse event	44.77	35.39	26	3920	37166	79703276
Ejection fraction decreased	43.83	35.39	25	3921	34552	79705890
Malaise	38.96	35.39	79	3867	489790	79250652
Excessive eye blinking	37.87	35.39	10	3936	1691	79738751

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01FD04	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors

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

Disease	Relation	SNOMED_ID	DOID
Advanced HER2positive gastric or gastroesophageal junction (GEJ) adenocarcinoma	indication	187734007
Metastatic human epidermal growth factor 2 positive carcinoma of breast	indication	459391000124109

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Receptor tyrosine-protein kinase erbB-2	Kinase	P04626	ERBB2_HUMAN	BINDING AGENT	Kd	8.13		SCIENTIFIC LITERATURE	DRUG LABEL
DNA topoisomerase 1	Enzyme	P11387	TOP1_HUMAN	INHIBITOR	IC50	7.51		SCIENTIFIC LITERATURE	DRUG LABEL

External reference:

ID	Source
CHEMBL4297844	ChEMBL_ID
D11529	KEGG_DRUG
C000614160	MESH_SUPPLEMENTAL_RECORD_UI
DB14962	DRUGBANK_ID
018237	NDDF
838469001	SNOMEDCT_US
838478007	SNOMEDCT_US
4039045	VANDF
C4726900	UMLSCUI
10516	INN_ID
132508503	PUBCHEM_CID
2267574	RXNORM
328684	MMSL
37925	MMSL
5384HK7574	UNII

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Enhertu	HUMAN PRESCRIPTION DRUG LABEL	1	65597-406	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	BLA	33 sections
Enhertu	HUMAN PRESCRIPTION DRUG LABEL	1	65597-406	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	BLA	33 sections
Enhertu	HUMAN PRESCRIPTION DRUG LABEL	1	65597-406	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	BLA	33 sections
Enhertu	HUMAN PRESCRIPTION DRUG LABEL	1	65597-406	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	BLA	33 sections