Herceptin Trastuzumab Powder for Concentrate for Solution for Infusion

1. Indications and Usage
Metastatic Breast Cancer: Treatment of HER2-positive metastatic breast cancer in combination with paclitaxel or docetaxel.
Adjuvant/Neoadjuvant Breast Cancer: Treatment of HER2-positive node-positive or node-negative (HER2-overexpressed only) early-stage breast cancer in combination with chemotherapy.
Metastatic Gastric Cancer: Treatment of HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma in combination with cisplatin and either fluoropyrimidine or capecitabine.
2. Dosage and Administration
Route of Administration: For Intravenous (IV) Infusion ONLY. Do not administer as an intravenous push or bolus.
Recommended Dosage:
Breast Cancer: 4 mg/kg IV loading dose, followed by 2 mg/kg weekly. Alternatively, a 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks.
Gastric Cancer: 4 mg/kg IV loading dose, followed by 6 mg/kg every 3 weeks.
Critical Administration Instructions:
Preparation: Aseptically withdraw the required volume and dilute in 0.9% Sodium Chloride Injection to a final concentration not exceeding 10 mg/mL.
Infusion Time: First infusion over 90 minutes. If tolerated, second infusion over 45 minutes. Subsequent infusions can be administered over 30 minutes.
3. Mechanism of Action
HER2 Binding: Trastuzumab binds with high affinity to extracellular domain IV of the human epidermal growth factor receptor 2 (HER2) protein.
Signal Inhibition: It inhibits proliferation of HER2-overexpressing tumor cells and downregulates HER2 expression.
Effector Functions: The Fc domain mediates antibody-dependent cellular cytotoxicity (ADCC), recruiting immune effector cells to target tumor cells.
4. Safety and Warnings
Cardiac Toxicity: Risk of left ventricular dysfunction and heart failure. Cardiac function (LVEF/Echo) must be assessed prior to and periodically during treatment.
Embryo-Fetal Toxicity: Can cause fetal harm, including oligohydramnios and infant renal impairment. Effective contraception is required.
Infusion-Related Reactions: Common during the first infusion; include fever, chills, nausea, and hypotension. Slower infusion rates may be required.
Pulmonary Toxicity: Fatal or life-threatening pulmonary reactions (e.g., interstitial pneumonitis) have been reported.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: Infusion-related reactions, pyrexia, nausea, vomiting, fatigue, diarrhea, and cardiac dysfunction.
Clinical Research Highlights: Pivotal trials (e.g., HERA, CLEOPATRA, ToGA) have established trastuzumab as a standard of care, demonstrating significant improvements in disease-free survival, overall survival, and response rates.
6. Drug Interactions
Anthracyclines: Concomitant use with doxorubicin or epirubicin increases the risk of cardiotoxicity. Anthracyclines should be completed before initiating trastuzumab.
Pertuzumab: Can be used in combination; monitor for overlapping adverse reactions.
Live Vaccines: Use of live vaccines should be avoided.
7. Pharmaceutical Information
Chemical Composition: Active Ingredient: Trastuzumab (recombinant DNA-derived humanized monoclonal antibody).
Appearance: White to off-white lyophilized cake or powder.
Packaging: Single-use vial (440 mg or 150 mg).
Storage: Store in the original carton at 2°C to 8°C. Do not freeze. Do not shake.