Doxorubicin

# Doxorubicin ## Overview Anthracycline chemotherapy antibiotic. Intercalates DNA, inhibits topoisomerase II, generates free radicals. Available as conventional doxorubicin HCl and pegylated liposomal formulation. ## Primary Indications - Breast cancer, lymphoma, leukemia, sarcoma, ovarian cancer, bladder cancer, multiple myeloma, small cell lung cancer ## Adult Dosing - **Conventional**: 60–75 mg/m² IV every 21 days - **Liposomal (Doxil)**: 50 mg/m² IV every 28 days - **Cumulative lifetime maximum**: 450–550 mg/m² (conventional); lower if prior chest radiation or cardiac risk factors - Exact dosing per chemotherapy protocol varies ## Pediatric Dosing - **Children**: 30–75 mg/m² IV every 21–28 days - Lower starting dose (25–30 mg/m²) often used for heavily pretreated patients - Cumulative max: 400–450 mg/m² (some protocols limit to 300 mg/m² with concomitant cardiotoxic agents) ## Dose Adjustments - **Hepatic**: Reduce dose for bilirubin 1.2–3.0 mg/dL (50% dose); bilirubin >3.0 mg/dL (75% reduction or hold) - **Renal**: No standard adjustment; caution with severe impairment - **Cardiac**: Hold if LVEF declines below institutional threshold ## Contraindications - Severe hepatic impairment - Baseline LVEF <50% or prior anthracycline at cumulative max - Severe myelosuppression - Recent MI or significant arrhythmia - Hypersensitivity to doxorubicin ## Adverse Effects - **Cardiotoxicity**: Acute arrhythmias; chronic dose-dependent cardiomyopathy (cumulative) - **Myelosuppression**: Neutropenia (dose-limiting), thrombocytopenia, anemia - **Mucositis/Stomatitis**: Dose-dependent - **Alopecia**: Universal - **Extravasation**: Severe tissue necrosis (vesicant) - **Nausea/Vomiting**: Moderate-high emetic risk - **Red/orange urine**: Harmless discoloration - **Secondary leukemia**: Rare, delayed ## Key Drug Interactions - **Trastuzumab**: Increased cardiotoxicity - **Paclitaxel**: May increase anthracycline exposure (sequence-dependent) - **Cyclophosphamide**: Additive cardiac toxicity - **Verapamil**: Increased doxorubicin levels - **Digoxin**: Reduced digoxin absorption - **Radiation**: Radiation recall with liposomal formulation ## Monitoring - Baseline: CBC, LFTs, bilirubin, LVEF (ECHO or MUGA), ECG - Before each cycle: CBC, LFTs, bilirubin - Every 2–4 cycles: LVEF reassessment (sooner if cumulative dose >300 mg/m²) - Signs/symptoms of heart failure, infection, mucositis ## Clinical Pearls - **Cardiac protection**: Dexrazoxane considered if cumulative doxorubicin >300 mg/m² in adults; use limited in pediatric settings - **Extravasation protocol**: Immediate infusion stop; apply cold compresses; consult plastic surgery - **Liposomal has different pharmacokinetics**: Longer circulation, reduced cardiotoxicity, but similar myelosuppression - **Infusion reactions**: Common with liposomal; premedicate with antihistamines/steroids - **Antiemetic**: Use NK1 antagonist + 5-HT3 antagonist + dexamethasone as per emetic risk --- *This information is for educational reference. Dosing, safety, and administration protocols vary by institution and patient-specific factors. Always verify current prescribing information and institutional guidelines before medication use.*