BLACK BOX WARNING
- cardiomyopathy — risk increases with cumulative dose above 550 mg/m²; prior mediastinal radiation lowers the threshold
- secondary AML/MDS
- severe myelosuppression
- extravasation causing severe local tissue injury and necrosis
- reduce dose with hepatic impairment
doxorubicin
Brand: Adriamycin, Doxil (liposomal)
⚠ BBW ISMP High Alert Prototype Drug
Drug Class: anthracycline antineoplastic antibiotic
Drug Family: antineoplastic
Subclass: prototype anthracycline
Organ Systems: hematology-oncology
Mechanism of Action
Intercalates into DNA, blocking topoisomerase II from resolving DNA strand breaks; generates reactive oxygen species via redox cycling; intercalation and free radical mechanisms contribute to DNA damage and apoptosis; cardiotoxicity results from iron-mediated ROS generation in cardiac mitochondria.
topoisomerase IIDNA intercalationreactive oxygen species generation
Indications
- breast cancer (adjuvant and metastatic)
- acute leukemias
- Hodgkin and non-Hodgkin lymphoma
- soft tissue sarcoma
- bladder, ovarian, thyroid cancers
- Kaposi sarcoma (liposomal formulation)
Contraindications
- doxorubicin hypersensitivity
- severe myocardial insufficiency
- previous total anthracycline dose near lifetime maximum
- recent MI or severe cardiac arrhythmia
Adverse Effects
Common
- myelosuppression (dose-limiting)
- alopecia (complete)
- nausea/vomiting
- red urine (not hematuria — normal discoloration from drug)
- mucositis
Serious
- cardiomyopathy (dose-dependent, cumulative, potentially irreversible)
- acute cardiotoxicity (arrhythmias during infusion)
- myelosuppression
- extravasation necrosis (vesicant — severe)
- secondary leukemia (AML)
- radiation recall
Pharmacokinetics (ADME)
| Absorption | IV only (significant first-pass inactivation if oral) |
| Distribution | large Vd; concentrates in tissues; limited CNS penetration |
| Metabolism | hepatic; active metabolite doxorubicinol (cardiotoxic) |
| Excretion | biliary/fecal (primary); renal minor; dose reduction required in hepatic impairment |
| Half-life | 20–48 hours (terminal) |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | 3-week cycles |
| Protein Binding | 75% |
| Vd | very large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| trastuzumab | both cardiotoxic; additive cardiomyopathy risk — avoid concurrent use; sequence trastuzumab after anthracycline | major |
| cyclosporine | increases doxorubicin levels and toxicity via P-gp inhibition | major |
| paclitaxel | sequence-dependent interaction; paclitaxel after doxorubicin increases cardiotoxicity | major |
Nursing Considerations
- Doxorubicin is a potent vesicant — peripheral IV access must be checked for patency before EACH cycle; extravasation causes severe, progressive tissue necrosis requiring surgical debridement.
- Obtain echocardiogram or MUGA scan to assess LVEF before initiating therapy, after cumulative doses of 250–300 mg/m², and before each additional dose once cumulative dose exceeds 400 mg/m².
- Warn patients that urine will appear red-orange for 1–2 days after treatment — reassure them this is the drug, not blood.
- Cumulative lifetime dose is typically limited to 550 mg/m² (450 mg/m² with prior mediastinal radiation) — communicate this limit across providers.
Clinical Pearls
- Doxorubicin's cardiomyopathy is mediated by iron-catalyzed free radical production in cardiac mitochondria (which lack catalase); dexrazoxane, an iron chelator, is FDA-approved to prevent doxorubicin cardiomyopathy by blocking iron-mediated ROS generation in the heart.
- The liposomal formulation (Doxil) achieves preferential tumor accumulation via the enhanced permeability and retention (EPR) effect while reducing cardiac exposure, significantly lowering cardiomyopathy risk.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.