DAUNOXOME

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DAUNOXOME (DAUNOXOME).

How it works

Daunorubicin intercalates between DNA base pairs, inhibiting topoisomerase II activity and preventing DNA replication and transcription. Liposomal encapsulation (DaunoXome) alters distribution, reducing cardiotoxicity and enhancing tumor delivery.

What the body does with it

Metabolism	Primarily hepatically metabolized via reduction to daunorubicinol by cytoplasmic reductases, and additionally by aldo-keto reductases and NADPH-dependent enzymes. Excretion: biliary and renal.
Excretion	Primarily biliary/fecal (40-50% as unchanged drug and metabolites); renal excretion accounts for approximately 5-15% as unchanged drug and metabolites over 5 days.
Half-life	Terminal elimination half-life is approximately 30-40 hours (range 20-48 h); prolonged compared to conventional doxorubicin due to liposomal encapsulation, allowing extended drug exposure.
Protein binding	Approximately 90-95% bound, primarily to plasma proteins (albumin); minimal displacement interactions reported.
Volume of Distribution	Vd is approximately 2-3 L/kg, indicating extensive tissue distribution; liposomal formulation concentrates in RES organs (liver, spleen) and tumors with leaky vasculature.
Bioavailability	Only administered intravenously; oral bioavailability is negligible (<5%) due to extensive first-pass metabolism and instability in GI tract.
Onset of Action	Intravenous: clinical effects (e.g., myelosuppression, antitumor activity) typically observed within 1-3 weeks after administration.
Duration of Action	Duration of action is prolonged; myelosuppression may persist for 2-3 weeks, with nadir counts occurring around day 10-14. Cumulative dose-limiting cardiotoxicity risk increases with total exposure.

Classification & Brands

Dosing & administration

60-80 mg/m² intravenously over 1 hour every 2-4 weeks.

Dosage form	INJECTABLE, LIPOSOMAL
Renal impairment	No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) and consider dose reduction.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: reduce dose by 50% or avoid use.
Pediatric use	60-80 mg/m² intravenously over 1 hour every 2-4 weeks; safety and efficacy not established in children under 2 years.
Geriatric use	No specific dose adjustment; monitor for increased toxicity due to age-related organ dysfunction.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DAUNOXOME (DAUNOXOME).

Breastfeeding	Contraindicated during breastfeeding. Daunorubicin is excreted into human milk; M/P ratio not available. Potential for severe adverse reactions (immunosuppression, neutropenia, carcinogenesis) in the nursing infant. Advise to discontinue breastfeeding for at least 7-10 days after last dose.
Teratogenic Risk	Daunorubicin (DaunoXome) is teratogenic in animal studies. First trimester: Avoid; major congenital malformations (cardiac, skeletal) reported. Second/third trimester: Use only if benefit outweighs risk; risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Fetal toxicity is dose-dependent.

Warnings & precautions

■ FDA Black Box Warning

DaunoXome should be administered under the supervision of a physician experienced in cancer chemotherapy. Severe myelosuppression occurs. Cardiac toxicity, including potentially irreversible cardiomyopathy, may occur, especially with cumulative doses >600 mg/m². Extravasation can cause severe tissue necrosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to daunorubicin or any component of DaunoXome. Severe hepatic impairment. Severe, pre-existing myelosuppression. Pregnancy (category D).

Clinical Precautions

Precautions

Monitor cardiac function (LVEF) regularly; cumulative dose limit 600 mg/m². Monitor blood counts for myelosuppression. Infusion reactions (hypotension, dyspnea) may occur. Not interchangeable with conventional daunorubicin.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

DAUNOXOME

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DAUNOXOME (DAUNOXOME).

How it works

What the body does with it

Metabolism	Primarily hepatically metabolized via reduction to daunorubicinol by cytoplasmic reductases, and additionally by aldo-keto reductases and NADPH-dependent enzymes. Excretion: biliary and renal.
Excretion	Primarily biliary/fecal (40-50% as unchanged drug and metabolites); renal excretion accounts for approximately 5-15% as unchanged drug and metabolites over 5 days.
Half-life	Terminal elimination half-life is approximately 30-40 hours (range 20-48 h); prolonged compared to conventional doxorubicin due to liposomal encapsulation, allowing extended drug exposure.
Protein binding	Approximately 90-95% bound, primarily to plasma proteins (albumin); minimal displacement interactions reported.
Volume of Distribution	Vd is approximately 2-3 L/kg, indicating extensive tissue distribution; liposomal formulation concentrates in RES organs (liver, spleen) and tumors with leaky vasculature.
Bioavailability	Only administered intravenously; oral bioavailability is negligible (<5%) due to extensive first-pass metabolism and instability in GI tract.
Onset of Action	Intravenous: clinical effects (e.g., myelosuppression, antitumor activity) typically observed within 1-3 weeks after administration.
Duration of Action	Duration of action is prolonged; myelosuppression may persist for 2-3 weeks, with nadir counts occurring around day 10-14. Cumulative dose-limiting cardiotoxicity risk increases with total exposure.

Classification & Brands

Dosing & administration

60-80 mg/m² intravenously over 1 hour every 2-4 weeks.

Dosage form	INJECTABLE, LIPOSOMAL
Renal impairment	No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) and consider dose reduction.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: reduce dose by 50% or avoid use.
Pediatric use	60-80 mg/m² intravenously over 1 hour every 2-4 weeks; safety and efficacy not established in children under 2 years.
Geriatric use	No specific dose adjustment; monitor for increased toxicity due to age-related organ dysfunction.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DAUNOXOME (DAUNOXOME).

Breastfeeding	Contraindicated during breastfeeding. Daunorubicin is excreted into human milk; M/P ratio not available. Potential for severe adverse reactions (immunosuppression, neutropenia, carcinogenesis) in the nursing infant. Advise to discontinue breastfeeding for at least 7-10 days after last dose.
Teratogenic Risk	Daunorubicin (DaunoXome) is teratogenic in animal studies. First trimester: Avoid; major congenital malformations (cardiac, skeletal) reported. Second/third trimester: Use only if benefit outweighs risk; risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Fetal toxicity is dose-dependent.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to daunorubicin or any component of DaunoXome. Severe hepatic impairment. Severe, pre-existing myelosuppression. Pregnancy (category D).