ELLENCE Injection is an anthracycline topoisomerase II inhibitor indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer (1).

• Administer intravenously in repeated 3- to 4-week cycles, either total dose on Day 1 of each cycle or divided equally and given on Days 1 and 8 of each cycle (2).
• The recommended starting dose of ELLENCE is 100 to 120 mg/m2. Dosage reductions are possible when given in certain combinations (2.1).
• Dosage adjustments after the first treatment cycle should be made based on hematologic and nonhematologic toxicities (2.2).
• Reduce dose in patients with hepatic impairment (2.2, 8.6, 12.3).
• Consider lower doses in patients with severe renal impairment (2.2, 8.7, 12.3).

Single use vials containing 2 mg epirubicin hydrochloride per mL as a sterile, preservative-free, ready-to-use solution (50 mg/25 mL and 200 mg/100 mL) (3)

Patients should not be treated with ELLENCE Injection if they have any of the following conditions: baseline neutrophil count < 1500 cells/mm3; cardiomyopathy and/or heart failure, recent myocardial infarction, severe arrhythmias; previous treatment with anthracyclines up to the maximum cumulative dose; hypersensitivity to epirubicin, other anthracyclines, or anthracenediones; or severe hepatic dysfunction (4).

• A dose-dependent, reversible leukopenia and/or neutropenia is the predominant manifestation of hematologic toxicity associated with ELLENCE and represents the most common acute dose-limiting toxicity (5.2).
• Cardiotoxicity is a known risk of anthracycline treatment and may be manifested by early (or acute) or late (delayed) events (5.3).
• The occurrence of secondary acute myelogenous leukemia, with or without a preleukemic phase, has been reported in patients treated with anthracyclines (5.4).
• Serum total bilirubin and AST levels should be eva luated before and during treatment with ELLENCE. Patients with elevated bilirubin or AST may experience slower clearance of drug with an increase in overall toxicity. Lower doses are recommended in these patients. Patients with severe hepatic impairment have not been eva luated (5.5).
• Serum creatinine should be assessed before and during therapy. Dosage adjustment is necessary in patients with serum creatinine >5 mg/dL. Patients undergoing dialysis have not been studied (5.6).
• ELLENCE may induce hyperuricemia as a consequence of the extensive purine catabolism that accompanies drug-induced rapid lysis of highly chemosensitive neoplastic cells (tumor-lysis syndrome) (5.7).
• Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including ELLENCE, may result in serious or fatal infections (5.8).
• Venous sclerosis may result from an injection into a small vessel or from repeated injections into the same vein. Extravasation of ELLENCE during the infusion may cause local pain, severe tissue lesions (vesication, severe cellulitis), and necrosis. Facial flushing, as well as local erythematous streaking along the vein, may be indicative of excessively rapid administration. It may precede local phlebitis or thrombophlebitis. Patients administered the 120-mg/m2 regimen of ELLENCE as a component of combination chemotherapy should also receive prophylactic antibiotic therapy with trimethoprim-sulfamethoxazole (e.g., Septra®, Bactrim®) or a fluoroquinolone (5.9).
• ELLENCE is emetigenic. Antiemetics may reduce nausea and vomiting; prophylactic use of antiemetics should be considered before administration of ELLENCE, particularly when given in conjunction with other emetigenic drugs (5.10).
• Administration of ELLENCE after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation (5.11)
• Thrombophlebitis and thromboembolic phenomena, including pulmonary embolism (in some cases fatal) have been coincidentally reported with the use of ELLENCE (5.12).
• ELLENCE can cause fetal harm when administered to a pregnant woman. Advise women of potential risk to the fetus (5.12).

• In early breast cancer, acute adverse events occurring in ≥10% of patients are leukopenia, neutropenia, anemia, thrombocytopenia, amenhorrhea, lethargy, nausea/vomiting, mucositis, diarrhea, infection, conjunctivitis/keratitis, alopecia, local toxicity and rash/itch (6).

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Do not administer Epirubicin in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored (7.1).
• Stop Cimetidine during treatment with ELLENCE (7.2).

• Nursing Mothers: Discontinue nursing prior to taking ELLENCE (8.3).
• Pediatric Use: Safety and effectiveness of ELLENCE in pediatric patients have not been established. Pediatric patients may be at greater risk for anthracycline-induced acute manifestations of cardiotoxicity and for chronic CHF (8.4).
• Geriatric Use: Care should be taken in monitoring toxicity when ELLENCE is administered to female patients ≥ 70 years of age. (8.5)