Doxorubicin (Liposomal) is a pegylated, liposomal formulation of the anthracycline antibiotic doxorubicin. It is designed to encapsulate doxorubicin within liposomes, which are microscopic vesicles composed of a phospholipid bilayer. This encapsulation significantly alters the pharmacokinetics and biodistribution compared to conventional doxorubicin. The pegylated (stealth) coating helps evade detection by the mononuclear phagocyte system, leading to prolonged circulation time and preferential accumulation in tumor tissues with leaky vasculature, a phenomenon known as the Enhanced Permeability and Retention (EPR) effect. This results in higher intratumoral concentrations and reduced exposure to healthy tissues, particularly the heart, thereby mitigating the risk of cardiotoxicity. It is a cytotoxic, non-cell-cycle specific antineoplastic agent.
Adult: Dose is based on Body Surface Area (BSA). **Kaposi's Sarcoma:** 20 mg/m² IV over 30 minutes, every 2-3 weeks. **Ovarian Cancer:** 50 mg/m² IV over 60 minutes, every 4 weeks. **Multiple Myeloma:** 30 mg/m² IV over 60 minutes on day 4 following bortezomib (which is given on days 1, 4, 8, & 11 of a 21-day cycle). Dose adjustments are based on hematological and non-hematological toxicity.
Note: **FOR IV INFUSION ONLY. NOT FOR INTRAMUSCULAR, SUBCUTANEOUS, OR INTRATHECAL USE. FATAL IF GIVEN INTRATHECALLY.** 1. Handle with cytotoxic precautions (gloves, gown, eye protection). 2. Dilute prescribed dose in 250 mL of 5% Dextrose Injection (D5W). **DO NOT USE SALINE or any other diluent.** 3. Do not mix with other drugs or heparin. Use a separate line. 4. Administer using a controlled infusion device over 30-60 minutes as per indication. 5. Use an IV line with a free-flowing IV solution (D5W) to prevent extravasation. Avoid veins over joints or in limbs with compromised circulation. 6. Observe for infusion reactions (flushing, shortness of breath, back pain). Pre-medication with antihistamines and corticosteroids is common.
The liposomal formulation delivers doxorubicin to tumor sites. Once internalized by tumor cells, doxorubicin exerts multiple cytotoxic effects: 1) **Intercalation into DNA:** It inserts itself between base pairs of the DNA double helix, disrupting DNA and RNA synthesis. 2) **Topoisomerase II Inhibition:** It stabilizes the topoisomerase II-DNA complex, preventing religation of DNA strands and causing double-strand breaks. 3) **Generation of Reactive Oxygen Species (ROS):** Through redox cycling, it generates semiquinone free radicals and superoxide anions, leading to oxidative damage of cellular membranes, proteins, and DNA. 4) **Disruption of Cellular Membranes:** It binds to cell membrane lipids, altering fluidity and function.
Pregnancy: **Category D:** Positive evidence of human fetal risk. Doxorubicin is teratogenic and embryotoxic. Can cause fetal harm. Contraindicated in pregnancy. 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, dizziness, or malaise. Patients should be cautioned about operating machinery or driving if affected.
| Other Cardiotoxic Agents (e.g., Trastuzumab, Cyclophosphamide, Daunorubicin) | Markedly increased risk of cardiomyopathy and congestive heart failure. Avoid concurrent use or monitor LVEF very closely. | Major |
| Cyclosporine, Verapamil | May increase intracellular doxorubicin concentrations, enhancing both efficacy and toxicity (especially hematological). | Moderate |
| Phenobarbital, Phenytoin | May increase hepatic metabolism of doxorubicin, reducing its plasma concentration and efficacy. | Moderate |
| Live Vaccines (e.g., MMR, Varicella, Yellow Fever) | Risk of disseminated infection due to immunosuppression. Contraindicated during treatment. | Major |
| Drugs metabolized by CYP2D6, CYP3A4 | Doxorubicin may inhibit these enzymes, increasing levels of substrates (e.g., some beta-blockers, antidepressants). | Moderate |
Same composition (Doxorubicin (Liposomal) (2mg/ml)), different brands: