Doxorubicin

🔹 1. Basic Information
Generic name: Doxorubicin Hydrochloride
Brand name: CIPLA-DOXORUBICIN
Drug class: Anthracycline cytotoxic antibiotic
Pharmacological class: A26 – Cytostatic agent
Formulation: Powder for solution for injection (IV use only)
Strengths: 10 mg and 50 mg vials
Mechanism of action: Intercalates between DNA base pairs, inhibiting DNA and RNA synthesis, and interacts with topoisomerase II to form DNA-cleavable complexes—resulting in inhibition of replication and cell death.

🔹 2. Indications
Treatment of:

• Hematologic malignancies: Acute lymphoblastic (ALL) and myelogenous leukaemia (AML), Hodgkin’s and non-Hodgkin’s lymphomas

• Solid tumours:

  • Breast carcinoma (including metastatic)

  • Ovarian carcinoma (with cisplatin/cyclophosphamide)

  • Bladder, thyroid, endometrial, testicular, prostate, cervical, head and neck carcinomas

  • Small cell lung carcinoma

  • Sarcomas (osteogenic, Ewing’s, soft tissue)

  • Neuroblastoma, myeloma

🔹 3. Dosing
Route: Intravenous (IV) only — not for IM, SC, or oral use
Solid tumours (monotherapy): 60–90 mg/m² every 3–4 weeks
Combination therapy: 30–60 mg/m² every 21 days
Alternative schedules:

• 0.6 mg/kg/day × 3 days

• 0.8 mg/kg/day × 2 days

• 1.6 mg/kg/day × 1 day
  Weekly regimen (alternative): 10–20 mg/m² weekly
  Acute leukaemia: 0.4–0.5 mg/kg/day for 3 days; repeat after 7–10 days depending on response
  Administration:

• Inject into the tubing of a free-flowing IV infusion of 0.9% NaCl or 5% glucose over ≥3–10 minutes

• Do not mix with other drugs or heparin (risk of precipitation)

🔹 4. Dose Modifications
Hepatic impairment:

Cumulative lifetime dose: Do not exceed 500 mg/m² (risk of irreversible cardiotoxicity).

🔹 5. Co-medications

• Commonly used in combination regimens, e.g.:

  • ABVD: Doxorubicin + Bleomycin + Vinblastine + Dacarbazine (Hodgkin’s)

  • BACOP: Doxorubicin + Cyclophosphamide + Vincristine + Prednisone + Bleomycin (Non-Hodgkin’s)

  • With cisplatin/cyclophosphamide in ovarian cancer

• Avoid concomitant cardiotoxic drugs (e.g., trastuzumab, other anthracyclines)

🔹 6. Contraindications

• Hypersensitivity to doxorubicin, other anthracyclines, or anthracenediones

• Persistent myelosuppression

• Severe hepatic impairment

• Cardiac disease (myocardial insufficiency, recent MI, severe dysrhythmias)

• Previous cumulative anthracycline dose >500 mg/m²

• Pregnancy and breastfeeding

🔹 7. Monitoring Requirements

• CBC: Before and during each cycle (neutropenia is dose-limiting)

• Cardiac function (LVEF): Baseline and periodic; monitor for cardiomyopathy

• Liver function (bilirubin, AST/ALT): Baseline and before each cycle

• Signs of extravasation: Pain, swelling, erythema

• Uric acid: Monitor during tumour lysis risk

🔹 8. Side Effects

🔹 9. Drug Interactions

• Additive toxicity: with other cytotoxics → ↑ myelosuppression & GI toxicity

• Cardiotoxic agents (e.g., trastuzumab, paclitaxel): ↑ risk of CHF

• Calcium channel blockers: May increase cardiotoxicity

• Hepatotoxic drugs: May alter doxorubicin metabolism and clearance

• Heparin/alkaline solutions: Physically incompatible — avoid mixing

🔹 10. Use in Special Populations

• Pregnancy/Lactation: Contraindicated (teratogenic, excreted in milk)

• Hepatic impairment: Dose reduction or avoid if severe

• Renal impairment: Use with caution

• Elderly: May require lower doses due to decreased clearance

• Obese patients: Reduced systemic clearance — monitor toxicity closely

🔹 11. Duration of Use / When to Stop the Drug
Continue until disease progression or unacceptable toxicity.
Discontinue if:

• Cumulative dose ≥500 mg/m² reached

• Irreversible cardiotoxicity or heart failure develops

• Persistent severe myelosuppression

• Hepatic function deteriorates significantly

🔹 12. Toxicity Management

REFERENCE: https://www.sahpra.org.za/wp-content/uploads/2020/02/Cipla-Doxorubicin_PI_Cipla_MCC-format-27-July-2012.pdf