Adult Dosing

Primary breast cancer involving axillary node tumor

• 100-120 mg/m² IV on day 1 of cycle repeated q3-4 wks
• Alt: 50-60 mg/m² IV given on day 1 and 8 of each cycle

Pre-existing bone marrow depression

• Start with lower dose 75-90 mg/m² IV on day 1 of cycle repeated q3-4 wks
• Alt: 32.5-45 mg/m² IV on day 1 and 8 of each cycle

Note:

• Administer prophylactic antibiotic therapy in patients receiving 120 mg/m² of epirubicin
• See package insert for toxicity related dose adjustments

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• As adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer

• Hypersensitivity to any of the ingredients of the product
• Hypersensitivity to anthracyclines or anthracenediones
• Baseline neutrophil count <1500 cells/mm³
• Severe myocardial insufficiency
• Recent myocardial infarction
• Severe arrhythmias
• Previous treatment with anthracyclines up to the maximum cumulative dose
• Severe hepatic dysfunction
• Pregnancy

• Epirubicin can cause severe local tissue necrosis if extravasation occurs during administration. Do not administer epirubicin by the intramuscular or subcutaneous route
• Myocardial toxicity, manifested as fatal congestive heart failure, may occur either during therapy, or months to years after discontinuation of therapy. The possibility of developing impaired myocardial function increases rapidly with increasing total cumulative doses of epirubicin in excess of 900 mg/m², it is estimated to be 0.9% at a total cumulative dose of 550 mg/m², 1.6% at a dose of 700 mg/m², 3.3% at 900 mg/m². The risk of cardiotoxicity increases with risk factors (active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, concomitant use of other cardiotoxic drugs). Cardiac toxicity with epirubicin may occur at lower cumulative doses whether or not cardiac risk factors are present
• Anthracyclines, including epirubicin, cause secondary acute myelogenous leukemia (AML) in patients with breast cancer. The occurrence of AML or MDS is more common when anthracyclines are given in combination with DNA-damaging anti-neoplastic agents or radiotherapy, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated. As per one study, the cumulative risk of developing treatment-related AML or myelodysplastic syndrome (MDS) in patients with breast cancer who received adjuvant treatment with epirubicin-containing regimens was estimated as 0.27% at 3 years, 0.46% at 5 years, and 0.55% at 8 years
• Reduce the dose in patients with impaired hepatic function
• Severe myelosuppression may occur with epirubicin therapy
• Administer epirubicin only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents

Renal Dose Adjustment (Based on serum creatinine)

• Severe renal impairment (serum creatinine >5 mg/dL): Reduce dose, amount not defined

Hepatic Dose Adjustment

• Bilirubin 1.2-3 mg/dL or AST 2-4 x ULN: Reduce starting dose by 50%
• Bilirubin > 3 mg/dL or AST > 4 x ULN: Reduce starting dose by 75%
• Severe hepatic impairment: Contraindicated

• Administer epirubicin only under the supervision of a qualified physician experienced in the use of cytotoxic therapy [US Black Box Warning]
• Before starting the epirubicin treatment, patient should recover from acute toxicities of prior cytotoxic treatment such as stomatitis, neutropenia, thrombocytopenia, and generalized infections
• Carefully evaluate baseline blood counts; serum levels of total bilirubin, AST, and creatinine; and cardiac function as measured by left ventricular ejection function (LVEF), before initiating epirubicin treatment
• Monitor patient carefully for possible clinical complications due to myelosuppression and cardiotoxicity. Provide necessary supportive care for the treatment of severe neutropenia and severe infectious complication
• Leukopenia and/or neutropenia are the predominant manifestations of epirubicin associated hematologic toxicity and are dose dependent and reversible, reaching nadir 10 to 14 days after treatment with recovery usually occurring by the 21st day
• Myelosuppression has been reported with epirubicin; severe myelosuppression results in fever, infections, sepsis/septicemia, septic shock, hemorrhage, tissue hypoxia, or death. Measure total and differential WBC, red blood cell (RBC), and platelet counts before and during each cycle of therapy and provide appropriate supportive measures if myelosuppressive complications occurs
• Cardiotoxicity, manifested by early or late events has been reported with anthracycline treatment. The risk of serious cardiac impairment can be decreased through regular monitoring of LVEF measured by multi-gated radionuclide angiography (MUGA) or echocardiography (ECHO), during the course of treatment. Discontinue epirubicin immediately at the first sign of impaired function [US Black Box Warning]
• Secondary AML or MDS has been reported with chemotherapy regimens containing anthracyclines (including epirubicin) and DNA-damaging antineoplastic agents, in combination with radiotherapy [US Black Box Warning]
• As epirubicin is metabolized and excreted predominantly by the hepatobiliary route, toxicity is enhanced by hepatic impairment. Hence evaluate hepatic function using conventional laboratory tests such as SGOT, SGPT, alkaline phosphatase, and bilirubin prior to individual dosing
• Epirubicin can cause fetal harm when administered to a pregnant woman, therefore use during pregnancy should be avoided. Women of childbearing age should be advised to avoid becoming pregnant and if the patient becomes pregnant during therapy, the patient should be apprised of the potential hazard to the fetus
• Injection into a small vessel or from repeated injections into the same vein can result in venous sclerosis. Follow the recommended administration procedures to minimize the risk of phlebitis/thrombophlebitis at the injection site
• Epirubicin associated extravasation causes local pain, severe tissue lesions (vesication, severe cellulitis) and necrosis. It is recommended to administer epirubicin slowly into the tubing of a freely running intravenous infusion
• Epirubicin is emetigenic hence use prophylactic antiemetics before administering

Cautions: Use cautiously in

• Severe renal impairment
• Hepatic impairment
• Cardiovascular diseases
• Concomitant hepatotoxic agent
• History of cardiovascular diseases
• Concomitant use of cardiotoxic agent
• Concomitant myelosuppressive agents
• Concomitant radiotherapy
• Pre-existing Myelosuppression
• Women of childbearing age

Pregnancy Category:D

Breastfeeding: Epirubicin is excreted in the milk of rats; it is unknown whether it is excreted in human milk. As many drugs, including other anthracyclines, are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, manufacturer advises to discontinue nursing prior to taking this drug.

• CV: CHF, asymptomatic drops in LVEF, sinus tachycardia, ECG abnormalities, tachyarrhythmias, atrioventricular and bundle-branch block, ventricular tachycardia, bradycardia, cardiomyopathy
• GI: Nausea/vomiting, mucositis, diarrhea, anorexia, mucositis, abdominal pain
• HEMA: Leukopenia, neutropenia, anemia, thrombocytopenia, febrile neutropenia, acute myelogenous leukemia, myelodysplastic syndrome, thromboembolism
• ENDO: Amenorrhea, hot flashes
• EENT: Conjunctivitis/keratitis
• DERM: Alopecia, rash/itch, local toxicity, skin and nail hyperpigmentation, flushes
• LOCAL: Venous sclerosis, extravasation, vesication, severe cellulitis, necrosis, local erythema, local phlebitis, thrombophlebitis
• GU: Tumor lysis syndrome
• MISC: Lethargy, fever, infection, chills

• Antineoplastic agent; forms complexes with DNA by intercalation between base pairs and inhibits nucleic acid (DNA and RNA) and protein synthesis
• Extensively and rapidly metabolized by the liver and also by other organs and cells including RBC
• Excreted mainly in bile/feces (34%); urine (27%)
• Half-life:
• Alpha: 3 minutes
• Beta: 2.5 hrs
• Gama: 33 hrs

US Trade Name(s)

• Ellence

US Availability

epirubicin (generic)

• INJ: 2 mg/mL (5, 25, 75, 100 mL vials)

Ellence

• INJ: 2 mg/mL (25, 100 mL vials)

Canadian Trade Name(s)

• Pharmorubicin

Canadian Availability

epirubicin (generic)

• INJ: 2 mg/mL (5, 25, 50, 75, 100 mL vials)
• PWDR for INJ: 50 mg/vial

UK Trade Name(s)

• Pharmorubicin

UK Availability

epirubicin (generic)

• INJ: 2 mg/mL (5, 10, 25, 50, 100 mL vials)
• PWDR for INJ: 50 mg/vial

Pharmorubicin

• INJ: 2 mg/mL (5, 10, 25, 100 mL vials)

Australian Trade Name(s)

• Pharmorubicin

Australian Availability

epirubicin (generic)

• INJ: 2 mg/mL (5, 25, 50, 100 mL vials)

Pharmorubicin

• PWDR for INJ: 50 mg/vial
• INJ: 2 mg/mL (5, 10, 25, 100 mL vials)

[Outline]

Hematology/Oncology

Antineoplastics

Anthracyclines