Details of the Drug

General Information of Drug (ID: DMZQOUX)

• Drug Name: Trastuzumab
• Synonyms: Herceptin; Herceptin (TN); Trastuzumab (INN); Trastuzumab (genetical recombination); Trastuzumab (genetical recombination) (JAN); Trastuzumab (ERBB2 mAb inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]
Inflammatory breast cancer	2C62	Approved	[2]
Lung cancer	2C25.0	Approved	[3]
Gastric adenocarcinoma	2B72	Application submitted	[4]
HER2-positive breast cancer	2C60-2C65	Application submitted	[4]
Gastric cancer	2B72	Investigative	[5]

• Therapeutic Class: Anticancer Agents
• Affected Organisms: Humans and other mammals
• ATC Code:
  L01FD01: Trastuzumab
  L01FD: HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors
  L01F: MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Antibody
• Sequence:
  >light chain (1 and 2)
  DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS
  RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP
  SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
  LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
  >heavy chain (1 and 2)
  EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY
  ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS
  ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
  GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPPKSCDKTHTCPPCPAPELLG
  GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
  NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
  ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
  WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
• ADMET Property:
  Clearance: The clearance of drug is 0.173-0.337 L/day [6]
  Half-life: The concentration or amount of drug in body reduced by one-half in 28 days [7]
  Metabolism: The drug is metabolized via the intracellularly into smaller peptides and amino acids [7]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Neoplasm related morbidities	Not Available	ERBB2	OTOAUNCK	[8]

• Cross-matching ID:
  UNII: P188ANX8CK
  DrugBank ID: DB00072
  TTD ID: D04WFL
  VARIDT ID: DR01171
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Not Available	[9]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Drug Response	[8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Erbb2 tyrosine kinase receptor (HER2)	DTT	ERBB2	5.67E-03	-1.26	-2.05

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Trastuzumab (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Trastuzumab and Roflumilast.	Asthma [CA23]	[10]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Trastuzumab and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[11]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Trastuzumab and Denosumab.	Low bone mass disorder [FB83]	[12]
Cladribine	DM3JDRP	Major	Additive immunosuppressive effects by the combination of Trastuzumab and Cladribine.	Mature B-cell leukaemia [2A82]	[10]
Alemtuzumab	DMZL3IV	Moderate	Additive myelosuppressive effects by the combination of Trastuzumab and Alemtuzumab.	Mature B-cell leukaemia [2A82]	[13]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Trastuzumab and Thalidomide.	Multiple myeloma [2A83]	[14]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Trastuzumab and Tecfidera.	Multiple sclerosis [8A40]	[15]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Trastuzumab and Siponimod.	Multiple sclerosis [8A40]	[16]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Trastuzumab and Fingolimod.	Multiple sclerosis [8A40]	[17]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Trastuzumab and Ocrelizumab.	Multiple sclerosis [8A40]	[18]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Trastuzumab and Ozanimod.	Multiple sclerosis [8A40]	[10]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Trastuzumab and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[19]
Efalizumab	DMCKL5V	Moderate	Additive immunosuppressive effects by the combination of Trastuzumab and Efalizumab.	Psoriasis [EA90]	[20]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Trastuzumab and Canakinumab.	Rheumatoid arthritis [FA20]	[21]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Trastuzumab and Rilonacept.	Rheumatoid arthritis [FA20]	[21]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Trastuzumab and Golimumab.	Rheumatoid arthritis [FA20]	[22]
Leflunomide	DMR8ONJ	Major	Additive myelosuppressive effects by the combination of Trastuzumab and Leflunomide.	Rheumatoid arthritis [FA20]	[11]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Trastuzumab when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[23]
Azathioprine	DMMZSXQ	Moderate	Additive myelosuppressive effects by the combination of Trastuzumab and Azathioprine.	Transplant rejection [NE84]	[16]
Ganciclovir	DM1MBYQ	Moderate	Additive myelosuppressive effects by the combination of Trastuzumab and Ganciclovir.	Virus infection [1A24-1D9Z]	[16]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Trastuzumab and Valganciclovir.	Virus infection [1A24-1D9Z]	[16]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5082).
• [2] Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32.
• [3] Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730.
• [6] FDA Approved Drug Products: Herceptin (trastuzumab) for intravenous injection
• [7] Trastuzumab. Oncologist. 2011;16(6):800-10. doi: 10.1634/theoncologist.2010-0035. Epub 2011 May 31.
• [8] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [9] Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study. Melanoma Res. 2004 Jun;14(3):207-10.
• [10] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [11] Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [12] Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
• [13] Product Information. Campath (alemtuzumab) Berlex, Richmond, CA.
• [14] Bennett CL, Nebeker JR, Samore MH, et al "The Research on Adverse Drug Events and Reports (RADAR) project." JAMA 293 (2005): 2131-40. [PMID: 15870417]
• [15] Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
• [16] Cerner Multum, Inc. "Australian Product Information.".
• [17] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [18] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [19] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
• [20] Product Information. Raptiva (efalizumab). Genentech, South San Francisco, CA.
• [21] Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
• [22] Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
• [23] CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]