Trastuzumab deruxtecan 

Action and Spectrum

Actions and spectrum: 

Trastuzumab deruxtecan is a humanized IgG1 anti-HER2 antibody which is used as a cancer-targeted therapy derived from HER2 gene mutation. It comes with a small molecule known as deruxtecan (DXd) that is a topoisomerase I inhibitor linked to a peptide. This drug is internalized upon the binding to HER2 on the malignant cells, and DXd is released through linker cleavage, which in turn causes DNA damage and apoptosis in cancer cells. As opposed to the rest of the antibody-drug conjugates, the cleavable peptide linker of trastuzumab deruxtecan boosts the therapy, even though it adds the difficulty of the same drug to non-targeted cells, thus inspiring drug resistance. 

Drug Interaction

Adverse Reaction

Frequency defined   

>10%  

Nausea (76%)  

Decreased white blood cell count (WBC) (74%)  

Decreased hemoglobin (64%)  

Decreased lymphocyte count (55%)  

Increased ALT (53%)  

Decreased neutrophil count (70%)  

Increased AST (67%)  

Decreased platelet count (52%)  

Vomiting (49%)  

Hypokalemia (35%)  

Constipation (34%)  

Anemia (33%)  

Increased blood alkaline phosphatase (49%)  

Fatigue (49%)  

Alopecia (37%)  

Musculoskeletal pain (31%)  

Respiratory tract infection (22%)  

Headache (22%)  

Diarrhea (29%)  

Decreased appetite (29%)  

Abdominal pain (21%)  

Increased blood bilirubin (20%)  

Stomatitis (20%)  

Decreased neutrophil count, Grade 3 or 4 (18%)  

Decreased lymphocyte count, Grade 3 or 4 (14%)  

Peripheral neuropathy (13%)  

Dizziness (13%)  

Decreased weight (17%)  

Increased blood creatinine (0.8%)  

1-10%  

Rash (10%)  

Vomiting, Grade 3 or 4 (3.8%)  

Hypokalemia (3.3%)  

Dizziness (10%)  

Interstitial lung disease (9%)  

Increased blood bilirubin (2.7%)  

<1%  

Increased ALT, Grade 3 or 4 (0.8%)  

Alopecia, Grade 3 or 4 (0.4%)  

Constipation, Grade 3 or 4 (0.9%)  

Stomatitis, Grade 3 or 4 (0.9%)  

Dry eye, Grade 3 or 4 (0.4%)  

Black Box Warning

Black box warning 

Embryo-fetal toxicity, pulmonary toxicity and pneumonitis may occur 

Contraindication / Caution

Contraindications/Caution 

Contraindications 

Hypersensitivity 

Cautions 

Cardiotoxicity  

Interstitial lung disease  

Hematological toxicity  

Hepatic impairment  

Renal impairment  

Infusion reactions  

Pregnancy   

Breastfeeding  

Other condition 

Pregnancy / Lactation

Pregnancy & breastfeeding: 

Pregnancy consideration: 

Safety and efficacy about the use of this drug in pregnancy is not available  

Breastfeeding warnings: 

Data about the excretion of the drug into human milk is not known 

Pregnancy category: 

• Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: There was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: There was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women. 
• Category D: Adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence, these categories of drugs need to be avoided by pregnant women. 
• Category N: No data for the drug under this category is available. 

Pharmacology

Pharmacology: 

Trastuzumab deruxtecan, a  HER-2 directed antibody is topoisomerase inhibitor. It belongs to the class of antibody-drug conjugate and developed by Astrazeneca. 

Pharmacodynamics: 

Trastuzumab functions in antitumor activities against only some kinds of HER2 positive breast cancer and current clinical trials are still in progress to affirm its efficacy. By combining a targeted antibody and a cytotoxic effect, trastuzumab deruxtecan can specifically kill tumor cells. 

Pharmacokinetics: 

Absorption  

Cmax of the drug was found to be 122µg/mL and AUC was 735 µg.day/mL. 

Distribution  

The volume of distribution was 2.77L as per a pharmacokinetic study. 

97% of the drug was bound to plasma proteins. 

Metabolism  

It gets broken down into aminoacids and smaller peptides through catabolism. Cathepsin L and B enzymes are supposed to be involved in the process of catabolism. 

Elimination and Excretion  

The drug mainly eliminates through feces. 

Half-life: 5.8 days 

Adminstartion

Administration: 

This is administered intravenously via an infusion through a central venous access device or a needle. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: trastuzumab deruxtecan 

Why do we use trastuzumab deruxtecan? 

This is a medication used to treat HER2-positive breast cancer. It’s important to note that trastuzumab/deruxtecan should be thoroughly evaluated based on the patient’s condition, including HER2 status, treatment history, overall health, and individual treatment goals.