trastuzumab: clinical use

Prescribing considerations

• Confirm eligible HER2 overexpression or amplification using an accurate, validated assay in a specialised laboratory.
• Treatment should be initiated by a clinician experienced in systemic anti-cancer therapy.
• Assess baseline cardiovascular history, examination and cardiac function, particularly previous anthracycline exposure and established cardiac risk factors.
• Check product name and route before every administration to prevent confusion between intravenous, subcutaneous and antibody–drug conjugate products.
• Record brand and batch number for biological-medicine traceability.
• Investigate new respiratory symptoms promptly because severe pulmonary reactions may be delayed.

Contraindications and cautions

• Hypersensitivity to trastuzumab, murine proteins or formulation excipients; the subcutaneous product is also contraindicated with hypersensitivity to hyaluronidase.
• Severe dyspnoea at rest caused by complications of advanced malignancy or requiring supplementary oxygen.

Monitoring

• Cardiac assessment before treatment and serial left ventricular function monitoring during treatment and follow-up.
• Observe for infusion- or injection-related reactions and ensure facilities for treating anaphylaxis are available.
• Monitor for heart-failure symptoms, pulmonary toxicity and infection; laboratory monitoring should reflect concomitant anti-cancer therapy.
• If pregnancy exposure occurs, arrange multidisciplinary maternal and fetal assessment, including amniotic-fluid monitoring when relevant.

Clinical pharmacology

Trastuzumab is a humanised IgG1 antibody that binds HER2 extracellular subdomain IV, inhibits ligand-independent signalling and receptor shedding, and promotes antibody-dependent cellular cytotoxicity. Elimination is non-linear, and clinically relevant persistence may continue for months after treatment stops.

Formulation and product differences

• The intravenous product is a powder requiring reconstitution and dilution for infusion; it must not be given as an intravenous push or by the subcutaneous route.
• The subcutaneous product is a ready-to-use solution containing recombinant human hyaluronidase to aid tissue dispersion; it is injected into the thigh and must not be given intravenously.
• The intravenous formulation includes licensed gastric and gastro-oesophageal junction cancer use; the selected subcutaneous formulation is licensed for breast cancer.
• Switching route may be considered by the specialist team, but route-specific product checks remain essential.

Solution for infusion

Route: Intravenous

Strengths: 150 mg, 420 mg

Injection

Route: Parenteral

Strengths: 600 mg