Doxorubicin is a cytotoxic anthracycline antibiotic derived from *Streptomyces peucetius* var. *caesius*. It is a cornerstone chemotherapeutic agent used primarily for its potent antineoplastic activity against a wide spectrum of hematological malignancies and solid tumors. It functions as a topoisomerase II inhibitor and intercalates into DNA, causing DNA damage and inhibiting macromolecular biosynthesis. Its use is limited by a well-characterized and potentially life-threatening dose-dependent cardiotoxicity.
Adult: Dose is based on Body Surface Area (BSA). Common regimens: 1) **Single Agent:** 60-75 mg/m² IV as a single dose, repeated every 21 days. 2) **Combination Therapy:** 40-60 mg/m² every 21-28 days. Dose adjustments are mandatory based on hematological and non-hematological toxicity.
Note: **FOR INTRAVENOUS USE ONLY. VESICANT.** Reconstitute 10mg vial with 5-10 mL of Water for Injection or Sodium Chloride 0.9%. Further dilute in 50-250 mL of Sodium Chloride 0.9% or 5% Dextrose. Administer via a slow IV infusion over 10-60 minutes through a free-flowing IV line, preferably via a central venous catheter. Flush line before and after administration. Monitor site closely for extravasation. Use strict aseptic technique. Protect from light.
Doxorubicin exerts its cytotoxic effects through multiple intercalative and non-intercalative mechanisms: 1) **Intercalation into DNA:** It inserts itself between base pairs of the DNA double helix, disrupting DNA and RNA synthesis. 2) **Inhibition of Topoisomerase II:** It stabilizes the topoisomerase II-DNA cleavable complex, preventing the religation of DNA strands and generating double-strand breaks. 3) **Generation of Reactive Oxygen Species (ROS):** The quinone moiety in its structure undergoes redox cycling, generating superoxide and hydroxyl radicals that cause lipid peroxidation and damage to cellular membranes, proteins, and DNA. 4) **Disruption of DNA Unwinding:** It inhibits helicase activity. 5) **Induction of Apoptosis:** The cumulative DNA damage and cellular stress trigger programmed cell death.
Pregnancy: **FDA Pregnancy Category D.** Doxorubicin is teratogenic and embryotoxic. Can cause fetal harm. Contraindicated, especially in first trimester. Women of childbearing potential must use effective contraception during and for at least 6 months after therapy. Men should use contraception during and for 3-6 months after therapy.
Driving: May cause fatigue, malaise, or dizziness. Patients should be cautioned about driving or operating machinery if affected.
| Trastuzumab, Cyclophosphamide (high-dose), Paclitaxel | Markedly increased risk of cardiotoxicity and heart failure. | Major |
| Cyclosporine, Verapamil | Inhibit P-glycoprotein efflux, increasing intracellular doxorubicin concentration and toxicity. | Major |
| Phenobarbital, Phenytoin | Induce hepatic metabolism, potentially reducing doxorubicin efficacy. | Moderate |
| Live Vaccines (e.g., MMR, Varicella, Yellow Fever) | Risk of disseminated vaccine-induced infection due to immunosuppression. | Major |
| Other Myelosuppressive Agents (e.g., 6-Mercaptopurine, Methotrexate) | Additive bone marrow toxicity. | Major |
| Dexrazoxane | Cardioprotectant; used to reduce risk of doxorubicin-induced cardiomyopathy. | Moderate (Beneficial) |
Same composition (Doxorubicin (Plain) (10mg)), different brands: