DAUNORUBICIN HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Anthracycline antibiotic that intercalates DNA, inhibits topoisomerase II, and generates free radicals causing DNA damage and cell death.
| Metabolism | Primarily hepatic metabolism via aldo-keto reductases to active metabolite daunorubicinol; also metabolized by CYP2D6 and carbonyl reductases. |
| Excretion | Primarily hepatobiliary: 40% as unchanged drug and metabolites in bile/feces. Renal excretion: ~25% unchanged within 24h. Minor fecal elimination of metabolites. |
| Half-life | Terminal elimination half-life: 24-48 hours (daunorubicinol, active metabolite, has similar t1/2). Clinical context: prolonged t1/2 due to extensive tissue binding, allowing weekly dosing. |
| Protein binding | ~50-70% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 15-25 L/kg (large, reflecting extensive tissue distribution, especially to heart and liver). |
| Bioavailability | Oral: negligible (<5%) due to first-pass metabolism and acid lability. IV: 100%. |
| Onset of Action | IV: onset of antineoplastic effect within 1-2 weeks (based on marrow suppression). Not applicable for other routes. |
| Duration of Action | Duration of myelosuppression: 3-4 weeks (nadir at 10-14 days). Cardiovascular toxicity (cardiomyopathy) may be delayed and irreversible. |
| Molecular Weight | 527.52 |
45-60 mg/m2 IV on days 1, 2, and 3 every 3-4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment guidelines; caution with severe renal impairment (CrCl <10 mL/min). |
| Liver impairment | Child-Pugh Class B: reduce dose by 25%; Class C: reduce dose by 50% or consider alternative therapy. |
| Pediatric use | 30-60 mg/m2 IV on days 1-3 of each cycle, with cycles repeated every 21-28 days. |
| Geriatric use | Start at lower end of dosing range due to increased risk of cardiotoxicity; monitor cardiac function closely. |
| 1st trimester | Contraindicated due to teratogenicity; risk of fetal malformations. |
| 2nd trimester | Avoid; may cause fetal harm including myelosuppression and cardiotoxicity. |
| 3rd trimester | Avoid; risk of neonatal myelosuppression and cardiac effects. |
Clinical note
Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.
| Placental transfer | Crosses placenta; evidence of fetal exposure with potential for fetal toxicity. |
| Breastfeeding | Contraindicated during breastfeeding; excreted into milk and may cause serious adverse effects in the nursing infant. Discontinue nursing or drug. |
| Lactation Rating |
■ FDA Black Box Warning
Cardiotoxicity (increased risk with cumulative doses, prior radiation, or concomitant cardiotoxic agents); severe myelosuppression; reduce dose in hepatic impairment; extravasation leading to severe tissue necrosis; do not administer intramuscularly or subcutaneously.
| Common Effects | Myelosuppression |
| Serious Effects |
Hypersensitivity to daunorubicin or any componentSevere hepatic impairmentSevere cardiac impairmentPregnancy
| Precautions | Monitor cardiac function (LVEF), blood counts, liver and renal function; risk of secondary leukemia; tumor lysis syndrome; immunosuppression; urate nephropathy due to hyperuricemia. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may inhibit CYP3A4 metabolism and increase toxicity. No other specific food interactions documented; advise a well-balanced diet, adequate hydration, and consumption of small, frequent meals to manage nausea. |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | First trimester: High risk of major congenital malformations, including central nervous system, cardiovascular, and skeletal defects. Second and third trimesters: Increased risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Anthracyclines are known teratogens; avoid use in pregnancy unless clearly needed. |
| Fetal Monitoring | Maternal: Baseline and serial echocardiography (ejection fraction), complete blood count, liver and renal function tests. Fetal: Regular ultrasound for growth, anatomy, and amniotic fluid volume; consider fetal echocardiography if exposure in second/third trimester. Neonatal: Monitor for myelosuppression and cardiac function. |
| Fertility Effects | May cause gonadal toxicity in both sexes, leading to amenorrhea, oligospermia, or azoospermia. Risk of permanent infertility increases with cumulative dose and age. Pre-treatment fertility preservation counseling recommended. |
| Clinical Pearls | Daunorubicin is an anthracycline antibiotic with potent cardiotoxicity; cumulative lifetime dose should not exceed 550 mg/m² (450 mg/m² with prior chest radiation). Administer via IV push over 2-3 minutes into a freely flowing IV line to prevent extravasation, which causes severe tissue necrosis. Premedicate with antiemetics as it is highly emetogenic. Monitor ECG and left ventricular ejection fraction before and during treatment. Avoid concurrent use with other cardiotoxic agents, and reduce dose in hepatic impairment (bilirubin >1.5 mg/dL). Urine may turn red-orange, which is harmless. |
| Patient Advice | Daunorubicin can cause serious heart damage; your heart function will be monitored before and during treatment. · Report any signs of infection, unusual bleeding, or bruising immediately. · You may experience nausea, vomiting, and hair loss; medications can help with nausea. · Your urine may become red-orange for 1-2 days after treatment; this is expected and not harmful. · Avoid grapefruit and grapefruit juice during treatment as it may increase side effects. · Drink plenty of fluids to help prevent kidney and bladder problems. · Use effective contraception during and for 6 months after treatment; do not breastfeed. |