Doxorubicin (Adriamycin)
Anthracycline Antibiotic
Commonly called "The Red Devil" due to its red color
Generic Name
Doxorubicin HCl
Brand Names
Adriamycin, Doxil (liposomal)
Drug Class
Anthracycline
Administration
IV Only (Vesicant)
⚠️ BLACK BOX WARNINGS
- CARDIOTOXICITY: Can cause cardiomyopathy and congestive heart failure. Risk increases with cumulative dose. Lifetime maximum: 450-550 mg/m²
- VESICANT: Severe local tissue necrosis if extravasation occurs
- MYELOSUPPRESSION: Severe bone marrow suppression may occur
- SECONDARY MALIGNANCIES: May increase risk of secondary acute myelogenous leukemia
- Must be administered by healthcare professionals experienced with chemotherapy
Overview
Doxorubicin is one of the most widely used chemotherapy drugs, effective against numerous cancers. It belongs to the anthracycline class and was first isolated from Streptomyces peucetius. Despite its efficacy, use is limited by cumulative cardiotoxicity.
Key Features
- Broad spectrum antineoplastic activity
- Red-orange color (stains urine red for 1-2 days)
- Dose-limiting cardiotoxicity
- Severe vesicant - requires careful administration
- Multiple mechanisms of action
- Component of many combination regimens
Available Formulations
- Conventional doxorubicin: Standard formulation
- Liposomal doxorubicin (Doxil): PEGylated liposomal, different toxicity profile
- Note: These are NOT interchangeable
FDA-Approved Indications
Solid Tumors
- Breast cancer: Adjuvant and metastatic
- Ovarian cancer: Various regimens
- Bladder cancer: Intravesical and systemic
- Thyroid cancer: Anaplastic and medullary
- Gastric cancer: Advanced disease
- Soft tissue sarcomas: First-line treatment
- Osteosarcoma: Part of standard therapy
- Small cell lung cancer: Combination therapy
- Neuroblastoma: Pediatric indication
- Wilms tumor: Pediatric indication
Hematologic Malignancies
- Hodgkin lymphoma: ABVD regimen
- Non-Hodgkin lymphomas: CHOP and other regimens
- Acute lymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML)
- Multiple myeloma: Various combinations
Common Combination Regimens
- AC: Adriamycin + Cyclophosphamide (breast)
- ABVD: Adriamycin + Bleomycin + Vinblastine + Dacarbazine (Hodgkin)
- CHOP: Cyclophosphamide + Hydroxydaunorubicin + Oncovin + Prednisone (NHL)
- FAC: 5-FU + Adriamycin + Cyclophosphamide (breast)
- VAD: Vincristine + Adriamycin + Dexamethasone (myeloma)
Mechanism of Action
Doxorubicin has multiple mechanisms of cytotoxicity:
- DNA intercalation: Inserts between DNA base pairs, disrupting replication
- Topoisomerase II inhibition: Prevents DNA repair, causes breaks
- Free radical generation: Creates reactive oxygen species damaging cells
- Membrane binding: Alters membrane function and fluidity
- Apoptosis induction: Triggers programmed cell death pathways
Cell Cycle Activity
- Cell cycle non-specific
- Most active in S phase
- Affects both dividing and non-dividing cells
Cardiotoxicity Management
❤️ Cardiotoxicity Risk Factors
- Cumulative dose >450-550 mg/m²
- Pre-existing heart disease
- Prior chest radiation
- Concurrent cardiotoxic drugs (trastuzumab)
- Age <18 or >65 years
- Hypertension
- Diabetes
Types of Cardiotoxicity
- Acute (within 1 week):
- Usually reversible
- Arrhythmias, EKG changes
- Pericarditis-myocarditis syndrome
- Early-onset chronic (within 1 year):
- Progressive cardiomyopathy
- Related to cumulative dose
- Late-onset chronic (years later):
- Can occur decades after treatment
- Important in pediatric survivors
Lifetime Cumulative Dose Limits
| Patient Population | Maximum Lifetime Dose |
|---|---|
| No risk factors | 450-550 mg/m² |
| With mediastinal radiation | 400 mg/m² |
| With concurrent trastuzumab | Consider alternatives or lower dose |
| Pediatric patients | 300-400 mg/m² |
| Pre-existing cardiac disease | Individualized, often lower |
Cardioprotective Strategies
- Dexrazoxane (Zinecard):
- FDA-approved cardioprotectant
- Consider when approaching dose limits
- May reduce antitumor efficacy (controversial)
- Continuous infusion: May reduce peak levels
- Liposomal formulation: Less cardiotoxic
- Dose fractionation: Weekly vs every 3 weeks
- ACE inhibitors/beta-blockers: May be protective
Dosing and Administration
Standard Dosing Regimens
| Regimen | Dose | Schedule |
|---|---|---|
| Single agent | 60-75 mg/m² | Every 21 days |
| Combination therapy | 40-60 mg/m² | Every 21-28 days |
| Weekly schedule | 15-20 mg/m² | Weekly |
| Dose-dense | 60 mg/m² | Every 14 days with growth factor |
| Continuous infusion | Various | 48-96 hour infusions |
Dose Modifications
Hepatic Impairment
- Bilirubin 1.2-3 mg/dL: Reduce dose by 50%
- Bilirubin 3.1-5 mg/dL: Reduce dose by 75%
- Bilirubin >5 mg/dL: Do not administer
Hematologic Toxicity
- ANC <1000/mm³ or platelets <50,000/mm³: Hold treatment
- Consider dose reduction for prolonged recovery
Side Effects
Common (>30%)
- Myelosuppression (nadir day 10-14)
- Nausea and vomiting
- Complete alopecia (hair loss)
- Mucositis/stomatitis
- Red urine discoloration
- Fatigue
Frequent (10-30%)
- Diarrhea
- Anorexia
- Hyperpigmentation (nails, skin)
- Radiation recall
- Hand-foot syndrome (with infusion)
- Amenorrhea
Serious/Rare
- Cardiomyopathy/CHF
- Extravasation necrosis
- Secondary leukemia
- Tumor lysis syndrome
- Hypersensitivity reactions
- Hepatotoxicity
🔴 Red Urine Discoloration
Doxorubicin causes harmless red-orange discoloration of urine for 1-2 days after administration. This is normal and not blood. Patients should be counseled to expect this.
Contraindications & Precautions
Absolute Contraindications
- Severe hypersensitivity to doxorubicin or components
- Severe myocardial insufficiency
- Recent myocardial infarction
- Severe persistent myelosuppression
- Severe hepatic impairment
- Previous treatment up to maximum cumulative dose
Use with Caution
- Pre-existing heart disease
- Previous anthracycline therapy
- Concurrent radiation therapy
- Hepatic impairment
- Active infections
- Elderly patients
Pregnancy and Fertility
- Pregnancy Category D: Can cause fetal harm
- Effective contraception required during and 6 months after
- May cause infertility in both males and females
- Consider fertility preservation before treatment
Drug Interactions
| Drug/Class | Interaction | Management |
|---|---|---|
| Trastuzumab | Increased cardiotoxicity | Avoid concurrent use, sequential preferred |
| Paclitaxel | Increased doxorubicin levels if given first | Give doxorubicin before paclitaxel |
| Cyclosporine | Increased doxorubicin levels | Monitor for increased toxicity |
| Phenobarbital | Increased doxorubicin clearance | May need dose adjustment |
| Phenytoin | Decreased phenytoin levels | Monitor phenytoin levels |
| Live vaccines | Risk of infection | Avoid during treatment |
| Radiation | Radiation recall, increased toxicity | Monitor closely |
Monitoring Parameters
Baseline Assessment
- CBC with differential
- Comprehensive metabolic panel
- Liver function tests (especially bilirubin)
- ECHO or MUGA scan (ejection fraction)
- EKG if indicated
- Pregnancy test if applicable
During Treatment
- Before each dose: CBC, liver function
- Cardiac monitoring:
- ECHO/MUGA at 300 mg/m² cumulative dose
- Before each dose after 400 mg/m²
- More frequent if risk factors
- Clinical assessment: Signs of CHF, infection
Long-term Follow-up
- Annual cardiac assessment for survivors
- Monitor for late cardiotoxicity
- Screen for secondary malignancies
Administration Guidelines
💉 Safe Administration Checklist
- ✓ Verify dose against lifetime cumulative dose
- ✓ Check recent cardiac function results
- ✓ Ensure patent IV access (prefer central line)
- ✓ Have extravasation kit available
- ✓ Use within 24 hours of preparation
- ✓ Protect from light during administration
- ✓ Monitor IV site continuously
Preparation
- Available as 2 mg/mL solution or powder
- Dilute in NS or D5W (stable 48 hours refrigerated)
- Final concentration: 0.01-2 mg/mL
- Do not mix with heparin or 5-FU (precipitate forms)
- Use non-PVC bags and tubing if prolonged contact
Administration Methods
- IV push: Over 3-10 minutes through running IV
- Short infusion: 15-30 minutes
- Continuous infusion: 48-96 hours (requires central line)
- Intravesical: For superficial bladder cancer
Extravasation Management
⚠️ VESICANT - Severe Tissue Damage Risk
Doxorubicin is a potent vesicant. Extravasation can cause severe tissue necrosis requiring surgical intervention.
Prevention
- Use central venous access when possible
- If peripheral IV: use large vein, new IV site
- Test patency with NS before administration
- Monitor continuously during infusion
- Educate patient to report pain, burning immediately
If Extravasation Occurs
- STOP infusion immediately
- Leave needle in place
- Aspirate residual drug through needle
- Remove needle
- Apply ice for 15-20 minutes QID × 24-48 hours
- Elevate extremity
- Consider dexrazoxane within 6 hours if large extravasation
- Do NOT apply pressure
- Photograph and document
- Surgical consultation for severe cases
Patient Counseling Points
Before Treatment
- Explain red urine is expected and harmless
- Hair loss will occur (usually by day 21)
- Importance of cardiac monitoring
- Contraception requirements
- Risk of infertility
During Treatment
- Report IV site pain immediately during infusion
- Signs of infection to watch for
- Mouth care to prevent stomatitis
- Sun protection (photosensitivity)
- Stay hydrated
Warning Signs to Report
- Shortness of breath or swelling (heart failure)
- Fever or signs of infection
- Severe nausea/vomiting
- Mouth sores
- Chest pain or irregular heartbeat
- Unusual bleeding or bruising
Long-term Considerations
- Lifelong cardiac monitoring needed
- Report doxorubicin history to all providers
- Cumulative dose tracking important
- Risk of late effects years later
Cost and Access
- Generic available: Yes - significantly reduces cost
- Average cost: $50-200 per dose (generic)
- Insurance coverage: Generally covered
- Patient assistance: Available through various programs
- Liposomal formulation: Significantly more expensive
Related Information
Medical Disclaimer
This drug information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment. Always consult with qualified healthcare providers regarding medications and treatment decisions. Dosing and protocols may vary by institution and indication.
References
- Doxorubicin Hydrochloride [package insert]. Various manufacturers. Revised 2025.
- National Comprehensive Cancer Network. NCCN Drugs & Biologics Compendium. 2026.
- Cardinale D, et al. Prevention of Anthracycline-Induced Cardiotoxicity. J Am Coll Cardiol. 2025.
- Micromedex Solutions. Doxorubicin monograph. Truven Health Analytics. 2026.
- Swain SM, et al. Congestive heart failure in patients treated with doxorubicin. Cancer. 2025.
- Children's Oncology Group. Long-term follow-up guidelines. Version 5.0. 2025.