ELLENCE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ELLENCE (ELLENCE).

How it works

ELLENCE (epirubicin) is an anthracycline cytotoxic antibiotic. It intercalates between DNA base pairs, inhibits topoisomerase II activity, and generates free radicals, leading to DNA damage and cell death.

What the body does with it

Metabolism	Primarily hepatic metabolism via aldoketoreductases and conjugation; also metabolized by glucuronidation and cytochrome P450 (CYP) enzymes, including CYP2B4 and CYP3A4.
Excretion	Primarily hepatobiliary excretion: ~40-50% of dose excreted as unchanged drug and metabolites in bile and feces. Renal excretion accounts for <10% (mostly as metabolites).
Half-life	Terminal elimination half-life is approximately 20-40 hours (mean ~30 hours). This supports a 3-week dosing interval to allow for recovery from myelosuppression.
Protein binding	Approximately 77% bound to plasma proteins, primarily albumin.
Volume of Distribution	Mean volume of distribution is 13-34 L/kg (average ~21 L/kg), indicating extensive tissue distribution and binding.
Bioavailability	IV only; oral bioavailability is negligible (<5%) due to extensive first-pass metabolism. Not administered orally.
Onset of Action	IV: Onset of antineoplastic effect occurs within days to weeks; peak plasma concentrations achieved immediately after injection.
Duration of Action	Duration of antineoplastic effect is prolonged, with myelosuppression nadir at 10-14 days and recovery by day 21. Cardiotoxicity may manifest months to years after treatment.

Classification & Brands

Dosing & administration

60-120 mg/m2 IV bolus or slow infusion on Day 1 every 21-28 days; or 20-30 mg/m2 IV daily for 3 days repeated every 28 days.

Dosage form	INJECTABLE
Renal impairment	No specific GFR-based dose adjustments required; caution in severe renal impairment (CrCl <10 mL/min) with potential increased toxicity.
Liver impairment	Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated or use at 50% reduction with caution.
Pediatric use	75-100 mg/m2 IV on Day 1 of 21-day cycles or 20-30 mg/m2 IV daily for 3 days every 28 days.
Geriatric use	No specific dose adjustment; consider increased susceptibility to myelosuppression and cardiotoxicity; monitor left ventricular ejection fraction.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ELLENCE (ELLENCE).

Breastfeeding	Contraindicated due to potential transfer into breast milk (M/P ratio not available). Theoretical risk of severe adverse effects in infants including bone marrow suppression and cardiotoxicity. Discontinue nursing or drug.
Teratogenic Risk	Pregnancy Category D. First trimester: High risk of teratogenicity including cardiac anomalies, skeletal defects, and fetal demise. Second and third trimesters: Risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Avoid use unless absolutely necessary.

Warnings & precautions

■ FDA Black Box Warning

Myocardial toxicity, including potentially fatal congestive heart failure, especially with cumulative doses >900 mg/m²; secondary acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS); extravasation leading to severe tissue necrosis; severe myelosuppression.

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe hepatic impairment (Child-Pugh class C), severe renal impairment (CrCl <30 mL/min), baseline neutrophil count <1500 cells/mm³, severe cardiac dysfunction, hypersensitivity to epirubicin or other anthracyclines.

Clinical Precautions

Precautions

Cardiotoxicity (cumulative dose-dependent), myelosuppression, secondary leukemia, extravasation, hepatotoxicity, renal impairment, immunosuppression, tumor lysis syndrome, and fetal harm.

Clinical Tips & Counseling

Drug interactions

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ELLENCE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ELLENCE (ELLENCE).

How it works

What the body does with it

Metabolism	Primarily hepatic metabolism via aldoketoreductases and conjugation; also metabolized by glucuronidation and cytochrome P450 (CYP) enzymes, including CYP2B4 and CYP3A4.
Excretion	Primarily hepatobiliary excretion: ~40-50% of dose excreted as unchanged drug and metabolites in bile and feces. Renal excretion accounts for <10% (mostly as metabolites).
Half-life	Terminal elimination half-life is approximately 20-40 hours (mean ~30 hours). This supports a 3-week dosing interval to allow for recovery from myelosuppression.
Protein binding	Approximately 77% bound to plasma proteins, primarily albumin.
Volume of Distribution	Mean volume of distribution is 13-34 L/kg (average ~21 L/kg), indicating extensive tissue distribution and binding.
Bioavailability	IV only; oral bioavailability is negligible (<5%) due to extensive first-pass metabolism. Not administered orally.
Onset of Action	IV: Onset of antineoplastic effect occurs within days to weeks; peak plasma concentrations achieved immediately after injection.
Duration of Action	Duration of antineoplastic effect is prolonged, with myelosuppression nadir at 10-14 days and recovery by day 21. Cardiotoxicity may manifest months to years after treatment.

Classification & Brands

Dosing & administration

60-120 mg/m2 IV bolus or slow infusion on Day 1 every 21-28 days; or 20-30 mg/m2 IV daily for 3 days repeated every 28 days.

Dosage form	INJECTABLE
Renal impairment	No specific GFR-based dose adjustments required; caution in severe renal impairment (CrCl <10 mL/min) with potential increased toxicity.
Liver impairment	Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated or use at 50% reduction with caution.
Pediatric use	75-100 mg/m2 IV on Day 1 of 21-day cycles or 20-30 mg/m2 IV daily for 3 days every 28 days.
Geriatric use	No specific dose adjustment; consider increased susceptibility to myelosuppression and cardiotoxicity; monitor left ventricular ejection fraction.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ELLENCE (ELLENCE).

Breastfeeding	Contraindicated due to potential transfer into breast milk (M/P ratio not available). Theoretical risk of severe adverse effects in infants including bone marrow suppression and cardiotoxicity. Discontinue nursing or drug.
Teratogenic Risk	Pregnancy Category D. First trimester: High risk of teratogenicity including cardiac anomalies, skeletal defects, and fetal demise. Second and third trimesters: Risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Avoid use unless absolutely necessary.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Clinical Precautions

Precautions

Cardiotoxicity (cumulative dose-dependent), myelosuppression, secondary leukemia, extravasation, hepatotoxicity, renal impairment, immunosuppression, tumor lysis syndrome, and fetal harm.

Clinical Tips & Counseling

Drug interactions

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