Nurses Compass
Drug Guide
Ado-trastuzumab Emtansine
Classification
Therapeutic: Antineoplastic agent (antibody-drug conjugate)
Pharmacological: HER2-targeted antibody-drug conjugate
FDA Approved Indications
- Treatment of HER2-positive breast cancer that has either received prior trastuzumab-based therapy and is locally advanced or metastatic
- Adjuvant therapy of HER2-positive early breast cancer (approved in some regions)
Mechanism of Action
Ado-trastuzumab Emtansine combines trastuzumab, an anti-HER2 monoclonal antibody, with emtansine (DM1), a cytotoxic agent. It binds to HER2-expressing cancer cells, is internalized, and releases DM1, which inhibits microtubule assembly, leading to cell cycle arrest and apoptosis.
Dosage and Administration
Adult: Approximate dose: 3.6 mg/kg IV every 3 weeks, administered as an infusion over 30-90 minutes.
Pediatric: Not indicated.
Geriatric: No specific dosage adjustment; use with caution and monitor response.
Renal Impairment: Limited data, use caution; no specific recommendations.
Hepatic Impairment: Use with caution; adjust dose as needed, especially in severe impairment.
Pharmacokinetics
Absorption: administered intravenously; bioavailability is complete.
Distribution: Widely distributed; volume of distribution approximately 4.5 L.
Metabolism: Metabolized by proteolytic degradation into amino acids; DM1 is released intracellularly.
Excretion: Primarily via feces; minimal renal excretion.
Half Life: Approximately 4 days.
Contraindications
- Hypersensitivity to ado-trastuzumab emtansine or its components
Precautions
- Monitor for cardiotoxicity, hepatotoxicity, and infusion reactions.
- Use in pregnancy and lactation only if clearly needed; potential risk to fetus and infant.
Adverse Reactions - Common
- Nausea (Common)
- Fatigue (Common)
- Musculoskeletal pain (Common)
- Neutropenia (Common)
Adverse Reactions - Serious
- Hepatotoxicity (ALT/AST elevations, hepatic failure) (Serious)
- Severe and fatal infusion-related reactions (Serious)
- Left ventricular systolic dysfunction (cardiotoxicity) (Serious)
- Peripheral neuropathy (Serious)
Drug-Drug Interactions
- Other cardiotoxic agents, hepatotoxic drugs, or drugs affecting blood counts.
Drug-Food Interactions
N/ADrug-Herb Interactions
N/ANursing Implications
Assessment: Monitor cardiac function (LVEF) prior to and during treatment, complete blood counts, and liver function tests.
Diagnoses:
- Risk for cardiotoxicity
- Risk for neutropenia or infection
- Risk for hepatotoxicity
Implementation: Administer IV infusion as scheduled, monitor for infusion reactions, monitor blood counts and liver function, educate patient on signs of toxicity.
Evaluation: Assess efficacy (tumor response), monitor adverse effects, adjust treatment as necessary.
Patient/Family Teaching
- Report signs of allergic reactions, new or worsening symptoms, chest pain, or signs of infection.
- Keep appointments for cardiac and blood tests.
- Inform about possible side effects and when to seek medical attention.
Special Considerations
Black Box Warnings:
- Hepatotoxicity, embryofetal toxicity, cardiomyopathy, and infusion reactions.
- Monitor LVEF regularly.
- Pregnancy risk: use contraception during and for at least 7 months after treatment.
Genetic Factors: No specific genetic considerations.
Lab Test Interference: May alter liver function tests and blood counts.
Overdose Management
Signs/Symptoms: Severe myelosuppression, anaphylaxis, cardiomyopathy.
Treatment: Supportive care, stop drug, monitor vital signs, treat symptoms accordingly.
Storage and Handling
Storage: Store in a refrigerator at 2-8°C. Do not freeze.
Stability: Stable for 28 days at 2-8°C after reconstitution.