Trastuzumab is a recombinant humanized monoclonal antibody (IgG1 kappa) that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 (HER2) protein. It is a targeted biologic therapy used in the treatment of HER2-positive breast and gastric/gastroesophageal junction cancers. The 440mg presentation is a lyophilized powder for concentrate for solution for infusion, designed for intravenous administration after reconstitution and dilution.
Adult: **Initial (Loading) Dose:** 8 mg/kg body weight by IV infusion over 90 minutes. **Subsequent (Maintenance) Dose:** 6 mg/kg body weight by IV infusion over 30-90 minutes every 3 weeks. *The 440mg vial is one of the available strengths used to achieve these weight-based doses.*
Note: **Reconstitution:** Add 20 mL of Bacteriostatic Water for Injection, BP (containing 1.1% benzyl alcohol) to the 440mg vial to yield a concentration of 21 mg/mL. Gently swirl, do not shake. **Dilution:** Withdraw calculated dose and add to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection, BP. Do not use dextrose solutions. Administer via IV infusion using a sterile, non-pyrogenic, low-protein binding 0.2 or 0.22 micron in-line filter. First infusion over 90 mins; subsequent infusions over 30 mins if prior infusion was well-tolerated. Observe patient for infusion-related reactions.
Trastuzumab mediates its antitumor effects through three primary mechanisms: 1) Inhibition of HER2 receptor dimerization and downstream PI3K/Akt and MAPK signaling pathways, leading to cell cycle arrest and apoptosis. 2) Induction of Antibody-Dependent Cellular Cytotoxicity (ADCC) by recruiting immune effector cells (e.g., Natural Killer cells) to attack HER2-overexpressing tumor cells. 3) Inhibition of extracellular domain shedding of the HER2 receptor.
Pregnancy: **Category D (US FDA).** Can cause oligohydramnios, fetal pulmonary hypoplasia, skeletal abnormalities, and fetal death. HER2 is involved in fetal cardiac development. Effective contraception is required during and for at least 7 months after therapy. Avoid use in pregnancy unless benefit outweighs significant risk.
Driving: Fatigue, dizziness, and chills may occur. Patients should be cautioned about operating machinery or driving if they experience these effects.
| Anthracyclines (e.g., Doxorubicin, Epirubicin) | Markedly increased risk of cardiotoxicity (congestive heart failure, decreased LVEF). | Major |
| Other Cardiotoxic Chemotherapy (e.g., Cyclophosphamide) | Potential additive cardiotoxic effects. | Moderate |
| Paclitaxel | Increases trastuzumab serum concentration by approximately 1.5-fold. | Moderate |
| Live Vaccines | Theoretical risk of disseminated infection due to immunosuppression. Avoid concomitant use. | Moderate |