Trastuzumab emtansine

Lyophilized powder for reconstitution:

• 100 mg/vial
• 160 mg/vial

• IV infusion over 90 minutes for the first dose, may shorten to 30 minutes if well tolerated.
• Do not administer as IV push or bolus.
• Monitor closely during and after infusion for hypersensitivity reactions.
• Use 0.9% NaCl only—incompatible with dextrose solutions.

Mechanism of Action:

• T-DM1 is a conjugate of:
  • Trastuzumab: Monoclonal antibody targeting HER2
  • DM1 (emtansine): Microtubule inhibitor (derivative of maytansine)
• After binding to HER2, T-DM1 is internalized; DM1 is released intracellularly, disrupting microtubules and inducing apoptosis.

Pharmacokinetics:

• Half-life: ~4 days
• Metabolism: Proteolytic degradation
• Excretion: Mostly via hepatic route

• Fatigue, headache
• Nausea, vomiting, constipation, diarrhea
• Elevated liver enzymes (ALT, AST)
• Thrombocytopenia, anemia
• Musculoskeletal pain
• Peripheral neuropathy

• Infusion-related reactions
• Hypokalemia
• Pulmonary toxicity
• Cardiac dysfunction (↓ LVEF)

• Known hypersensitivity to trastuzumab emtansine or any of its components
• Pregnancy
• Severe hepatic impairment

• Strong CYP3A4 inhibitors or inducers may alter emtansine levels:
  • Avoid co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)
• Anticoagulants/NSAIDs: Use with caution due to bleeding risk (thrombocytopenia)