Enhertu Trastuzumab Deruxtecan Powder for Injection

1. Indications and Usage
HER2-Positive Breast Cancer:
Indicated for the treatment of adult patients with HER2-positive unresectable or metastatic breast cancer who have received two or more prior anti-HER2 based regimens.
HER2-Low Expressing Breast Cancer:
Indicated for the treatment of adult patients with HER2-low expressing unresectable or metastatic breast cancer who have received prior chemotherapy in the metastatic setting or in the neoadjuvant/adjuvant setting.
HER2-Positive Gastric Cancer:
Indicated for the treatment of adult patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
2. Dosage and Administration
Recommended Dosage:
Breast Cancer: 5.4 mg/kg administered intravenously once every 3 weeks.
Gastric Cancer: 6.4 mg/kg administered intravenously once every 3 weeks.
Administration Instructions:
Reconstitution and Dilution: Must be reconstituted with Sterile Water for Injection and diluted in 100 mL of 5% Dextrose Injection. Do not use Sodium Chloride Injection (0.9% NaCl) for reconstitution or dilution as it may cause particle formation.
Infusion: Administer as an intravenous infusion. The initial infusion should be administered over 90 minutes. If the first infusion is well tolerated, subsequent infusions may be administered over 30 minutes.
Pre-medication: Administer anti-emetics prior to each dose to prevent nausea and vomiting.
3. Mechanism of Action
Antibody-Drug Conjugate (ADC):
Trastuzumab deruxtecan is an ADC composed of a humanized anti-HER2 monoclonal antibody covalently linked to a topoisomerase I inhibitor (deruxtecan or DXd) via a cleavable tetrapeptide-based linker.
Physiological Effect:
The antibody targets and binds to HER2 on the cell surface, leading to internalization of the ADC. The linker is cleaved by intracellular proteases, releasing the cytotoxic payload (DXd) into the cell, which induces DNA damage and apoptosis. The high membrane permeability of DXd allows it to exert a bystander effect on adjacent tumor cells.
4. Safety and Warnings
Interstitial Lung Disease (ILD)/Pneumonitis:
ILD/pneumonitis, including fatal cases, has been reported. Monitor patients for pulmonary symptoms. Permanently discontinue for Grade 2 or higher ILD/pneumonitis.
Embryo-Fetal Toxicity:
Can cause fetal harm. Advise females of reproductive potential to use effective contraception.
5. Adverse Reactions
Most Common:
Nausea, fatigue, alopecia, vomiting, diarrhea, musculoskeletal pain, constipation, headache, dyspnea, decreased appetite, rash, and cough.
6. Drug Interactions
CYP3A Substrates:
DXd is metabolized by CYP3A4. Monitor for adverse reactions when co-administered with sensitive CYP3A substrates.
7. Pharmaceutical Information
Storage:
Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake.