CERUBIDINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CERUBIDINE (CERUBIDINE).

How it works

Daunorubicin intercalates between DNA base pairs, inhibiting topoisomerase II and preventing DNA replication and transcription, leading to cell death.

What the body does with it

Metabolism	Primarily hepatic metabolism via aldo-keto reductases to daunorubicinol (active metabolite), and further via CYP2D6 and carbonyl reductases.
Excretion	Primarily hepatic metabolism with biliary excretion (about 40% as unchanged drug and metabolites in bile). Renal excretion accounts for approximately 8-15% of the dose as unchanged drug and metabolites. Fecal elimination is less than 20%.
Half-life	Triphasic elimination: initial half-life 30 min (distribution), intermediate 3-5 hours (metabolism), terminal half-life 20-30 hours (slow elimination from tissues). Clinically relevant for scheduling and myelosuppression monitoring.
Protein binding	Approximately 50-70% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is high, ranging from 15-30 L/kg, indicating extensive tissue binding and distribution, particularly into erythrocytes and tissues.
Bioavailability	Oral bioavailability is less than 5% due to extensive first-pass metabolism; therefore, not administered orally. IV administration results in 100% bioavailability.
Onset of Action	IV: Onset within minutes to hours, with peak plasma concentration immediately after infusion. Clinical effect (antileukemic) observed within days.
Duration of Action	Duration of cytotoxic effect persists for several days; myelosuppression nadir occurs at 10-14 days, lasting 2-3 weeks. Cardiac toxicity may be delayed and cumulative.

Classification & Brands

Dosing & administration

45–60 mg/m² IV on days 1–3 every 21–28 days, or 30–60 mg/m² IV daily for 3 days every 3 weeks.

Dosage form	INJECTABLE
Renal impairment	CrCl 10–50 mL/min: reduce dose by 25%; CrCl <10 mL/min: reduce dose by 50%. Hemodialysis: administer after dialysis; dose reduction by 50%.
Liver impairment	Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	25–45 mg/m² IV on days 1–3 every 21 days; neonates: <10 kg: 1 mg/kg IV daily for 3–5 days.
Geriatric use	Initiate at lower end of dose range (30 mg/m²/day for 3 days) due to increased myelotoxicity; monitor renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CERUBIDINE (CERUBIDINE).

Breastfeeding	Contraindicated during breastfeeding. Daunorubicin is excreted into breast milk; M/P ratio unknown due to limited data. Potential for severe adverse effects in nursing infant including immunosuppression, cardiotoxicity, and carcinogenesis.
Teratogenic Risk	Pregnancy Category D. First trimester: High risk of congenital malformations including craniofacial, skeletal, CNS, and cardiac defects. Second and third trimesters: Risk of fetal growth restriction, prematurity, and neonatal myelosuppression.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Severe myelosuppression; cumulative dose-related cardiotoxicity; extravasation with tissue necrosis; secondary leukemias.

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe myelosuppression; previous anthracycline therapy at maximum cumulative dose; severe hepatic impairment; severe cardiac disease; pregnancy.

Clinical Precautions

Precautions	Bone marrow suppression; cardiac toxicity (cumulative doses >550 mg/m²); hepatic and renal impairment; tumor lysis syndrome; immunosuppression.
Food/Dietary	Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition increasing toxicity. No other specific food restrictions reported.

Clinical Tips & Counseling

Clinical Pearls

Drug interactions

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CERUBIDINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CERUBIDINE (CERUBIDINE).

How it works

Daunorubicin intercalates between DNA base pairs, inhibiting topoisomerase II and preventing DNA replication and transcription, leading to cell death.

What the body does with it

Metabolism	Primarily hepatic metabolism via aldo-keto reductases to daunorubicinol (active metabolite), and further via CYP2D6 and carbonyl reductases.
Excretion	Primarily hepatic metabolism with biliary excretion (about 40% as unchanged drug and metabolites in bile). Renal excretion accounts for approximately 8-15% of the dose as unchanged drug and metabolites. Fecal elimination is less than 20%.
Half-life	Triphasic elimination: initial half-life 30 min (distribution), intermediate 3-5 hours (metabolism), terminal half-life 20-30 hours (slow elimination from tissues). Clinically relevant for scheduling and myelosuppression monitoring.
Protein binding	Approximately 50-70% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is high, ranging from 15-30 L/kg, indicating extensive tissue binding and distribution, particularly into erythrocytes and tissues.
Bioavailability	Oral bioavailability is less than 5% due to extensive first-pass metabolism; therefore, not administered orally. IV administration results in 100% bioavailability.
Onset of Action	IV: Onset within minutes to hours, with peak plasma concentration immediately after infusion. Clinical effect (antileukemic) observed within days.
Duration of Action	Duration of cytotoxic effect persists for several days; myelosuppression nadir occurs at 10-14 days, lasting 2-3 weeks. Cardiac toxicity may be delayed and cumulative.

Classification & Brands

Dosing & administration

45–60 mg/m² IV on days 1–3 every 21–28 days, or 30–60 mg/m² IV daily for 3 days every 3 weeks.

Dosage form	INJECTABLE
Renal impairment	CrCl 10–50 mL/min: reduce dose by 25%; CrCl <10 mL/min: reduce dose by 50%. Hemodialysis: administer after dialysis; dose reduction by 50%.
Liver impairment	Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	25–45 mg/m² IV on days 1–3 every 21 days; neonates: <10 kg: 1 mg/kg IV daily for 3–5 days.
Geriatric use	Initiate at lower end of dose range (30 mg/m²/day for 3 days) due to increased myelotoxicity; monitor renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CERUBIDINE (CERUBIDINE).

Breastfeeding	Contraindicated during breastfeeding. Daunorubicin is excreted into breast milk; M/P ratio unknown due to limited data. Potential for severe adverse effects in nursing infant including immunosuppression, cardiotoxicity, and carcinogenesis.
Teratogenic Risk	Pregnancy Category D. First trimester: High risk of congenital malformations including craniofacial, skeletal, CNS, and cardiac defects. Second and third trimesters: Risk of fetal growth restriction, prematurity, and neonatal myelosuppression.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Severe myelosuppression; cumulative dose-related cardiotoxicity; extravasation with tissue necrosis; secondary leukemias.

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe myelosuppression; previous anthracycline therapy at maximum cumulative dose; severe hepatic impairment; severe cardiac disease; pregnancy.

Clinical Precautions

Precautions	Bone marrow suppression; cardiac toxicity (cumulative doses >550 mg/m²); hepatic and renal impairment; tumor lysis syndrome; immunosuppression.
Food/Dietary	Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition increasing toxicity. No other specific food restrictions reported.

Clinical Tips & Counseling

Clinical Pearls

Drug interactions

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