DOXORUBICIN HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Anthracycline antibiotic that intercalates between DNA base pairs, inhibits topoisomerase II, and generates free radicals, leading to DNA damage and cell death.
| Metabolism | Primarily hepatically metabolized by aldo-keto reductases to doxorubicinol (active metabolite). Also metabolized by cytochrome P450 enzymes (minor pathway). |
| Excretion | Primarily biliary/fecal (40-50% as unchanged drug and metabolites); renal excretion accounts for approximately 5-12% as unchanged drug and metabolites within 5 days. |
| Half-life | Terminal elimination half-life: 20-48 hours (mean ~30 hours). The prolonged terminal phase reflects slow release from tissue binding (e.g., DNA intercalation). |
| Protein binding | Approximately 70-85% bound, primarily to albumin. |
| Volume of Distribution | Vd: 20-30 L/kg (indicating extensive tissue distribution and binding to intracellular components, particularly DNA). |
| Bioavailability | Oral bioavailability is <5% due to extensive first-pass metabolism and P-glycoprotein efflux. IV bioavailability is 100%. |
| Onset of Action | IV: Onset within 1-3 minutes; peak effect at 30 minutes to 1 hour. Intravesical: Onset within 2-4 hours. |
| Duration of Action | IV: Clinical effects (e.g., myelosuppression, cardiac effects) extend over weeks; elimination half-life of 30 hours results in detectable levels for 5-7 days. |
60-75 mg/m² IV bolus every 21 days as a single agent; or 40-60 mg/m² IV bolus every 21-28 days in combination regimens. Maximum cumulative lifetime dose: 450-550 mg/m² (or 400 mg/m² with prior chest radiation or concurrent cyclophosphamide).
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl < 10 mL/min: administer 75% of normal dose. No adjustment for CrCl ≥ 10 mL/min. |
| Liver impairment | Child-Pugh Class A (5-6 points): administer 100% of dose. Child-Pugh Class B (7-9 points): administer 50% of dose. Child-Pugh Class C (10-15 points): administer 25% of dose or consider alternative therapy. |
| Pediatric use | 30-75 mg/m² IV every 21-28 days, not to exceed adult dose. For body surface area < 0.5 m², dose based on weight: 1-2 mg/kg IV every 21-28 days. |
| Geriatric use | No specific dose adjustment recommended, but consider increased risk of cardiotoxicity and myelosuppression; monitor LVEF and cardiac function closely. Start at lower end of dosing range (60 mg/m²) and titrate based on tolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.
| Breastfeeding | Doxorubicin is excreted into human breast milk. The milk-to-plasma (M/P) ratio is approximately 0.5–3.5. Because of the potential for serious adverse effects in the nursing infant (including immunosuppression and carcinogenesis), breastfeeding is contraindicated during treatment and for at least 10 days after the last dose. |
| Teratogenic Risk | Doxorubicin is pregnancy category D. First trimester exposure is associated with a high risk of major congenital malformations (up to 20-30%), including cardiovascular, neural tube, and skeletal defects. Second and third trimester exposure increases risk of intrauterine growth restriction, preterm birth, and fetal myelosuppression. Use is contraindicated in pregnancy unless absolutely necessary. |
■ FDA Black Box Warning
Myocardial damage including acute left ventricular failure may occur with cumulative doses >550 mg/m² (450 mg/m² with prior mediastinal radiation). Extravasation can cause severe tissue necrosis. Secondary acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) reported. Suppression of bone marrow function.
| Common Effects | Myelosuppression |
| Serious Effects |
Hypersensitivity to doxorubicin or any component of the formulation, severe hepatic impairment (Child-Pugh class C), severe myocardial insufficiency (pre-existing cardiomyopathy), recent myocardial infarction, severe arrhythmias, baseline neutrophil count <1500/mm³ (or platelet count <100,000/mm³), prior cumulative anthracycline therapy near maximum lifetime dose, breastfeeding.
| Precautions | Cardiotoxicity (cumulative dose-dependent, increased risk with prior anthracycline use or mediastinal radiation), myelosuppression, extravasation (severe tissue necrosis), secondary malignancies (AML/MDS), hepatic impairment (reduce dose), tumor lysis syndrome, immunosuppression (live vaccines contraindicated), embryo-fetal toxicity, acute infusion-related reactions. |
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| Fetal Monitoring | Maternal: Complete blood count with differential, cardiac function (echocardiogram or MUGA scan) before each cycle, liver and renal function tests, and monitoring for signs of infection, bleeding, or heart failure. Fetal: Ultrasound for growth and anatomy, fetal echocardiography if exposure during first trimester, and assessment for intrauterine growth restriction and preterm labor. |
| Fertility Effects | Doxorubicin is highly gonadotoxic. It can cause irreversible ovarian failure in females (premature menopause, decreased fertility) and azoospermia or oligospermia in males. Fertility preservation (e.g., oocyte or sperm cryopreservation) should be considered prior to treatment. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to potential CYP3A4 interaction. Maintain adequate hydration to reduce risk of uric acid nephropathy. No other specific dietary restrictions; however, because of the risk of nausea, small frequent meals may be helpful. |
| Clinical Pearls | Monitor left ventricular ejection fraction (LVEF) before and during therapy; cumulative doses >450-550 mg/m² increase cardiomyopathy risk. Observe IV administration carefully to prevent extravasation, which causes severe tissue necrosis; treat with dexrazoxane or topical cooling. Urine may appear red for 1-2 days post-dose, which is benign. Prophylactic antiemetics recommended. Risk of secondary malignancies (e.g., AML) with prolonged use. |
| Patient Advice | This drug may cause heart damage; report any shortness of breath, swelling in the legs, or irregular heartbeat to your doctor immediately. · Your urine may turn reddish-orange for 1-2 days after treatment; this is harmless and not blood. · Avoid consuming grapefruit or grapefruit juice during treatment as it may affect how the drug works. · Do not receive live vaccines while on this medication and for 6 months after completing therapy. · Use effective contraception during treatment and for at least 6 months after the last dose; this drug can harm a fetus. · Report any signs of infection (fever, sore throat) or unusual bleeding/bruising immediately. · This drug can cause severe nausea and vomiting; take antiemetics as prescribed. |