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. Its clinical utility is limited by its significant and potentially life-threatening cardiotoxicity, which is cumulative and dose-dependent.
Adult: **Single agent:** 60-75 mg/m² body surface area (BSA) administered as a single intravenous infusion every 21 days. **Combination therapy:** Commonly 40-60 mg/m² every 21-28 days (e.g., in CHOP, ABVD, FAC regimens). Dose is ALWAYS calculated based on BSA (m²).
Note: **FOR INTRAVENOUS USE ONLY.** Reconstitute 50mg vial with 25 mL of Sodium Chloride Injection (0.9%) to yield 2 mg/mL. Further dilute in 50-250 mL of 0.9% NaCl or 5% Dextrose. Administer via a free-flowing IV line, preferably through a central venous catheter or a large, patent peripheral vein. Infusion duration is typically 15-60 minutes. **MUST** monitor for extravasation. Flush line before and after administration.
Doxorubicin exerts its cytotoxic effects through multiple, intercalation-dependent and independent mechanisms: 1) **Intercalation into DNA:** It inserts itself between DNA base pairs, disrupting DNA and RNA synthesis. 2) **Topoisomerase II Inhibition:** It stabilizes the topoisomerase II-DNA cleavable complex, preventing DNA religation and leading to double-strand breaks and apoptosis. 3) **Generation of Reactive Oxygen Species (ROS):** The quinone moiety undergoes enzymatic reduction to a semiquinone radical, which reacts with oxygen to produce superoxide and hydroxyl radicals, causing oxidative damage to cellular membranes, proteins, and DNA. This mechanism is particularly implicated in cardiotoxicity due to lower antioxidant defenses in cardiac tissue.
Pregnancy: **FDA Pregnancy Category D.** Can cause fetal harm. There is positive evidence of human fetal risk (teratogenicity, cardiac toxicity). Contraindicated. Women of childbearing potential must use effective contraception during and for at least 6 months after therapy.
Driving: May cause severe fatigue, dizziness, or weakness. Patients should be cautioned against driving or operating machinery, especially during periods of peak fatigue or if experiencing side effects.
| Cyclophosphamide | Increased risk of hemorrhagic cystitis and cardiotoxicity; synergistic antitumor effect. | Major |
| Trastuzumab | Markedly increased risk of cardiac dysfunction (CHF, reduced LVEF). Concurrent use is contraindicated. | Major |
| Paclitaxel | Alters doxorubicin pharmacokinetics (increased AUC), increasing risk of neutropenia and mucositis. Sequence matters (give doxorubicin before paclitaxel). | Major |
| Verapamil | May increase intracellular doxorubicin concentration by inhibiting P-glycoprotein efflux, potentially increasing toxicity. | Moderate |
| Phenobarbital / Phenytoin | May increase hepatic metabolism of doxorubicin, reducing its efficacy. | Moderate |
| Live Vaccines (e.g., MMR, Varicella) | Risk of disseminated infection due to immunosuppression. Contraindicated. | Major |
| Dexrazoxane | Cardioprotectant; used to reduce the incidence and severity of cardiomyopathy. Administered before doxorubicin. | Moderate (Therapeutic) |