Makindo Medical Notes

🚨 Cardiotoxicity alert: The lifetime cumulative dose of doxorubicin should usually not exceed 500 mg/m². 💡 Risk rises significantly beyond this threshold due to anthracycline-induced cardiomyopathy. 👉 Always check baseline and serial LVEF (echocardiogram or MUGA scan).

📖 About

• Doxorubicin (Adriamycin) is a potent anthracycline chemotherapy drug.
• Acts by interfering with DNA processes and generating free radicals.
• Broadly used in both solid tumours and haematological malignancies.

🧬 Mechanism of Action

• 📌 DNA intercalation: slips between DNA base pairs → blocks replication & transcription.
• 📌 Topoisomerase II inhibition: prevents DNA unwinding → halts cell division.
• 📌 Free radical generation: oxidative damage to lipids, proteins & DNA → apoptosis.
• ❤️ Cardiotoxicity partly linked to free radical damage in myocardium (low antioxidant defences).

🎯 Indications

• Breast & ovarian cancer
• Bladder cancer (systemic or intravesical use)
• Lymphomas (Hodgkin & non-Hodgkin)
• Leukaemias (ALL, AML)
• Soft-tissue sarcomas, Osteosarcoma, Ewing’s sarcoma
• Wilms’ tumour, Neuroblastoma
• Multiple myeloma, Thyroid carcinoma, Endometrial carcinoma
• Other rare paediatric & adult tumours

💉 Administration

• IV infusion is standard – extravasation is dangerous → tissue necrosis ⚠️.
• Can be given intravesically for bladder tumours (superficial carcinoma, prophylaxis after TURBT).
• Dose calculated on body surface area (BSA), usually in cycles.
• Often combined with other drugs (e.g., ABVD regimen for Hodgkin lymphoma).

⚠️ Cautions

• Baseline cardiac assessment essential (echo or MUGA scan).
• Avoid in severe liver disease (hepatic metabolism).
• Care with prior chest radiotherapy or other cardiotoxic drugs (trastuzumab, cyclophosphamide).

🚫 Contraindications

• Active infection or neutropenia (low WCC).
• Severe hepatic impairment.
• Severe pre-existing cardiac disease.

🔄 Interactions

• Other cardiotoxic agents (trastuzumab, cyclophosphamide, paclitaxel) ↑ risk of heart failure.
• Digoxin pre-treatment has been shown in some studies to reduce cardiotoxicity.
• Check BNF for full list of drug–drug interactions.

🌡️ Patient advice: Seek urgent medical help if temperature >37.5°C OR if feeling acutely unwell (shaky, sore throat, cough, diarrhoea, urinary symptoms) → may indicate neutropenic sepsis.

💥 Side Effects

• 🔴 Red-orange urine discolouration (benign, but warn patients!)
• 📉 Myelosuppression (↓ WCC, Hb, platelets)
• 💇 Alopecia
• ❤️ Cardiotoxicity: cumulative, dose-related cardiomyopathy & CHF
• GI upset: nausea, vomiting, mucositis
• Skin/tissue necrosis if extravasated

📚 References

• SPC for Doxorubicin
• BNF – Doxorubicin