DAUNORUBICIN HYDROCHLORIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Anthracycline antibiotic that intercalates DNA, inhibits topoisomerase II, and generates free radicals causing DNA damage and cell death.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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	Contraindicated during breastfeeding. Daunorubicin is likely excreted in human milk; potential for serious adverse reactions in nursing infants (e.g., myelosuppression, cardiotoxicity). M/P ratio not established. Discontinue breastfeeding during therapy and for at least 10 days after last dose.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Hypersensitivity to daunorubicin or other anthracyclines; severe hepatic impairment; severe myelosuppression; baseline left ventricular ejection fraction (LVEF) below institutional lower limit; concurrent use of live vaccines; pregnancy (teratogenic).

Clinical Precautions

Precautions

Monitor cardiac function (LVEF), blood counts, liver and renal function; risk of secondary leukemia; tumor lysis syndrome; immunosuppression; urate nephropathy due to hyperuricemia.

Clinical Tips & Counseling

Drug interactions

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