Trustuzumab

🔹 1. Basic Information

Generic name: Trastuzumab
Brand name: Herceptin SC
Drug class: Monoclonal antibody (anti-HER2)
Formulation: Solution for subcutaneous injection
Strength: 600 mg trastuzumab + 10,000 U recombinant human hyaluronidase per 5 mL
Mechanism of Action:
Binds to HER2 receptors on tumour cells → inhibits proliferation of HER2-overexpressing cells → mediates antibody-dependent cellular cytotoxicity (ADCC).

🔹 2. Indications

HER2-positive Breast Cancer

• Early breast cancer: Adjuvant use following surgery, chemotherapy, and radiotherapy (if applicable).

• Metastatic breast cancer: Monotherapy after ≥1 chemotherapy line, or with paclitaxel or docetaxel in first-line treatment.

• Locally advanced breast cancer: Neoadjuvant use with chemotherapy before surgery, then continued as adjuvant monotherapy.

HER2-positive Metastatic Gastric or Gastro-oesophageal Junction Adenocarcinoma

• In combination with capecitabine or 5-FU and cisplatin in previously untreated, HER2-positive disease.

🔹 3. Dosing & Administration

• Dose: 600 mg subcutaneously every 3 weeks (q3w).

• Route: SC injection into the thigh over ~2–5 minutes (alternate thighs each dose).

• No loading dose required.

• Do not administer IV.

• Duration: Continue until disease progression or for 1 year (18 cycles) in the adjuvant setting.

• If a dose is missed → administer as soon as possible, then maintain 3-week intervals thereafter.

🔹 4. Dose Modifications

• No dose reductions; temporarily interrupt if toxicity occurs.

• Cardiotoxicity:

  • Withhold if LVEF falls ≥10% from baseline or below 50%.

  • Resume if LVEF recovers within 4–8 weeks.

  • Permanently discontinue for symptomatic or persistent heart failure.

• Hypersensitivity / Injection reactions:

  • Interrupt or stop treatment; give supportive therapy as needed.

🔹 5. Co-medications

• Common combinations:

  • Paclitaxel, docetaxel, or pertuzumab (breast cancer).

  • Capecitabine or cisplatin (gastric cancer).

• Avoid concurrent anthracyclines (e.g. doxorubicin, epirubicin) due to additive cardiotoxicity.

🔹 6. Contraindications

• Hypersensitivity to trastuzumab, hyaluronidase, or excipients.

• Severe dyspnoea at rest, oxygen dependence, or advanced pulmonary disease.

🔹 7. Monitoring Requirements

• Cardiac monitoring:

  • Baseline LVEF (ECHO/MUGA) → every 3 months during therapy and every 6 months for 2 years after completion (if adjuvant).

• Clinical monitoring:

  • Observe for 6 hours after first injection and 2 hours after subsequent doses.

• Watch for:

  • Heart failure symptoms (dyspnoea, oedema, cough)

  • Pulmonary reactions

  • Injection or hypersensitivity reactions

🔹 8. Side Effects & Management

Very common (>10%)
Injection-site reactions, fatigue, chills, nausea, diarrhoea, headache, fever, myalgia, rash, cough, decreased appetite
→ Usually mild to moderate; manage symptomatically

Common (1–10%)
Cardiac dysfunction, infection, neutropenia, hypertension, dyspnoea, arthralgia
→ Monitor and treat supportively

Uncommon (<1%)
Anaphylaxis, angioedema, severe pulmonary reactions, interstitial pneumonitis
→ Discontinue permanently; emergency management

Serious adverse events:

• Congestive heart failure (dose-limiting)

• Severe hypersensitivity or anaphylaxis

• Pulmonary toxicity

🔹 9. Use in Special Populations

• Pregnancy: Contraindicated; may cause oligohydramnios or foetal renal dysfunction.

  • Use contraception during and for 7 months after last dose.

• Breastfeeding: Avoid during and for 7 months after therapy.

• Elderly: No dose adjustment required.

• Renal/Hepatic impairment: No adjustment required.

• Paediatrics: Not established.

🔹 10. Duration of Use / When to Stop

Continue until disease progression (metastatic) or for 1 year (18 cycles) in adjuvant therapy.
Permanently discontinue if:

• Symptomatic heart failure or persistent LVEF decline

• Severe hypersensitivity or anaphylaxis

• Severe pulmonary toxicity

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2023/04/Herceptin-SC-PI_23Dec2022.pdf