ELLENCE
Clinical safety rating
cautionComprehensive clinical and safety monograph for ELLENCE (ELLENCE).
Comprehensive clinical and safety monograph for ELLENCE (ELLENCE).
Adjuvant therapy in patients with axillary node-positive breast cancerTreatment of metastatic breast cancerOff-label: treatment of ovarian cancer, gastric cancer, small cell lung cancer, and soft tissue sarcoma
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.
| 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. |
| Molecular Weight | 543.5 |
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. |
| 1st trimester | Avoid. Embryotoxic and teratogenic in animals; risk of fetal harm. |
| 2nd trimester | Avoid. Risk of fetal toxicity; use only if clearly needed. |
| 3rd trimester | Avoid. Potential for neonatal myelosuppression and cardiotoxicity near term. |
Clinical note
Comprehensive clinical and safety monograph for ELLENCE (ELLENCE).
| Placental transfer | Epirubicin crosses the placenta. Detectable levels found in fetal tissues. |
| Breastfeeding | It is not known whether epirubicin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Lactation Rating | L5 |
| 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. |
| Fetal Monitoring | Monitor maternal CBC, cardiac function (LVEF by echocardiogram or MUGA), liver and renal function. Fetal monitoring via ultrasound for growth and anatomy q3-4weeks if used during pregnancy. |
| Fertility Effects | May cause irreversible ovarian failure resulting in premature menopause and infertility in premenopausal women. Spermatogenesis impairment in males with potential for azoospermia. |
■ 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.
| Serious Effects |
Hypersensitivity to epirubicin or other anthracyclinesBaseline neutrophil count <1500 cells/mm^3Severe hepatic impairment (Child-Pugh class C)Severe myocardial insufficiency, recent myocardial infarction, severe arrhythmiasPrevious treatment with maximum cumulative doses of anthracyclinesAcute systemic infections
| Precautions | Cardiotoxicity (cumulative dose-dependent), myelosuppression, secondary leukemia, extravasation, hepatotoxicity, renal impairment, immunosuppression, tumor lysis syndrome, and fetal harm. |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment as they may affect drug metabolism. No other specific food interactions known. |
| Clinical Pearls | Ellence (epirubicin) is an anthracycline chemotherapeutic agent. It is a vesicant; extravasation can cause severe tissue necrosis. Administer via a freely flowing IV line. Premedicate with antiemetics. Monitor for cardiotoxicity, which is dose-dependent and may be cumulative. Total lifetime dose should not exceed 900-1000 mg/m². Assess cardiac function (LVEF) before and during treatment. Urine may turn red for 1-2 days after administration. Avoid live vaccines. |
| Patient Advice | Ellence can cause severe nausea and vomiting; take antiemetics as prescribed. · Report any pain, redness, or swelling at the injection site immediately. · Urine may appear red for 1-2 days after treatment; this is normal. · Use effective contraception during and for at least 6 months after treatment. · Avoid live vaccines (e.g., MMR, varicella) while on this medication. · Report signs of infection (fever, chills), unusual bleeding or bruising, shortness of breath, or chest pain. · Do not breastfeed while taking Ellence. |
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