Trastuzumab Deruxtecan
Trastuzumab Deruxtecan Uses, Dosage, Side Effects, Food Interaction and all others data.
Trastuzumab Deruxtecan is a HER-2 directed antibody attached to a topoisomerase inhibitor that is approved for use in certain types of metastatic, unresectable breast cancer. It is classified as an antibody-drug conjugate. The cleavable peptide linker used to bind the antibody and drug in this product distinguishes it from other members of its class. Trastuzumab Deruxtecan has been granted FDA approval for specific patients with HER-2 positive breast cancer who have failed other treatments.
Promising results from a clinical trial prompted accelerated FDA approval for this indication on December 20, 2019. Trastuzumab Deruxtecan was developed by Daiichi Sankyo in collaboration with AstraZeneca. The continued approval of this drug will depend on the confirmation of its beneficial effects in ongoing clinical trials.
Trastuzumab demonstrates antitumor activity against certain types of HER2 positive breast cancer, however, clinical trials are still ongoing to confirm its efficacy. By exploiting both targeted antibody and cytotoxic effects, trastuzumab deruxtecan can effectively destroy tumors.
| Trade Name | Trastuzumab Deruxtecan |
| Generic | Trastuzumab deruxtecan |
| Trastuzumab deruxtecan Other Names | fam-trastuzumab deruxtecan-nxki, Trastuzumab deruxtecan |
| Type | |
| Protein binding | The Dxd portion of the drug has a plasma protein binding estimated at 97%. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Trastuzumab Deruxtecan is an antibody used to treat certain types of unresectable or metastatic HER-2 positive breast cancer.
Trastuzumab Deruxtecan is indicated for the treatment of adult patients with HER-2 positive breast cancer that is unresectable or metastatic and was previously treated with at least 2 anti-HER2-based regimens while the cancer was metastatic.
Continued approval will depend on the results of clinical trial results confirming its clinical benefit.
Trastuzumab Deruxtecan is also used to associated treatment for these conditions: HER2/Neu-positive Breast Cancer
How Trastuzumab Deruxtecan works
Trastuzumab Deruxtecan is a humanized anti-HER2 IgG1 antibody, targeting cancer cause by mutation of the HER2 gene. In addition, the small molecule portion of this drug, deruxtecan (DXd), is a topoisomerase I inhibitor. It is attached to the antibody by a peptide linker. After trastuzumab deruxtecan binds to HER2 found on malignant cells, it is internalized and linker cleavage occurs through the actions of lysosomal enzymes. After it is released through cleavage, DXd causes targeted DNA damage and apoptosis in cancer cells, due to the ability to cross cell membranes.
Normally, drugs in this class (antibody-drug conjugates) present a challenge. The monoclonal antibody accurately targets cancer cells, however exert limited killing action. The addition of a cytotoxic agent (a topoisomerase I inhibitor in this case) effectively kills dividing cancer cells, including those in the healthy tissues, leading to various adverse effects. The peptide linker used to formulate this drug is cleavable, which is unique to other antibody-drug conjugates, allowing for increased efficacy and reduced drug resistance to topoisomerase.
Toxicity
LD50 and overdose information are not currently available, but effects of an overdose are likely to impact the lungs, heart, and circulatory system, leading to significant toxicity.
Food Interaction
No interactions found.Volume of Distribution
The estimated volume of distribution of trastuzumab deruxtecan in the central compartment is 2.77 L, according to a population based pharmacokinetic study. Pharmacokinetic studies found that the unchanged drug is distributed in the blood and is not significantly retained in tissues.
Elimination Route
The Cmax of trastuzumab deruxtecan at normal therapeutic doses was 122 μg/mL (20%). The AUC of trastuzumab deruxtecan was 735 μg·day/mL (31%).
Half Life
In a pharmacokinetic study, the median elimination half-life of trastuzumab deruxtecan was about 5.8 days.
Clearance
Trastuzumab Deruxtecan is rapidly cleared from systemic circulation. Estimated systemic clearance of trastuzumab deruxtecan is 0.42 L/day, according to a population pharmacokinetic analysis. DXd showed a systemic clearance of about 19.2 L/h.
Elimination Route
A pharmacokinetic study revealed that this drug was mainly excreted in the feces. Another study determined that 67% of a dose was excreted in the feces. Unmetabolized DXd was found in the urine during a pharmacokinetic study.
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