HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ELLENCE safely and effectively. See full prescribing information for ELLENCE.
ELLENCE® (epirubicin hydrochloride injection)
Initial U.S. Approval: 1999
WARNING: CARDIAC TOXICITY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, and SEVERE MYELOSUPPRESSION
See full prescribing information for complete boxed warning.
- Cardiac Toxicity: Myocardial damage, including acute left ventricular failure, can occur with ELLENCE. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 0.9% at a cumulative dose of 550 mg/m2, 1.6% at 700 mg/m2, and 3.3% at 900 mg/m2. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction (LVEF) before and regularly during and after treatment with ELLENCE (5.1).
- Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including ELLENCE (5.2).
- Extravasation and Tissue Necrosis: Extravasation of ELLENCE can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area (5.3).
- Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur (5.4).
RECENT MAJOR CHANGES
|Warnings and Precautions, Embryo-Fetal Toxicity (5.11)||07/2019|
INDICATIONS AND USAGE
ELLENCE is an anthracycline topoisomerase inhibitor indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer (1).
DOSAGE AND ADMINISTRATION
- The recommended starting dose of ELLENCE is 100 to 120 mg/m2. Dosage reductions are possible when given in certain combinations (2.2).
- 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 (2.2).
- Consider use of antiemetics when given in conjunction with other emetigenic drugs (2.1).
- Patients administered the 120 mg/m2 regimen of ELLENCE should receive prophylactic antibiotic therapy (2.1).
- Adjust dosage after the first treatment cycle based on hematologic and nonhematologic toxicities (2.3).
- Reduce dose in patients with hepatic impairment (2.3, 8.6).
- Consider lower doses in patients with severe renal impairment (2.3, 8.7).
DOSAGE FORMS AND STRENGTHS
Injection: 50 mg/25 mL (2 mg/mL), 200 mg/100 mL (2 mg/mL) solution in single-dose vials (3).
- Severe myocardial insufficiency (4).
- Recent myocardial infarction (4).
- Severe persistent drug-induced myelosuppression (4).
- Severe hepatic impairment (4).
- Severe hypersensitivity to ELLENCE, other anthracyclines, or anthracenediones (4).
WARNINGS AND PRECAUTIONS
- Use in Patients with Hepatic Impairment: Monitor serum total bilirubin and AST levels before and during treatment with ELLENCE. In patients with elevated serum AST or serum total bilirubin, dosage reductions or discontinuation may be required (2.3, 5.5).
- Tumor Lysis Syndrome: Evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment. Consider hydration, urine alkalinization, and prophylaxis with allopurinol to minimize potential complications of hyperuricemia and tumor lysis syndrome (5.7).
- Thrombophlebitis and Thromboembolic Events: Thrombophlebitis and thromboembolic events, including pulmonary embolism (in some cases fatal) have been reported with the use of ELLENCE. Venous sclerosis may result from an injection into a small vessel or from repeated injections into the same vein (5.9).
- Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including ELLENCE, may result in serious or fatal infections (5.7).
- Potentiation of Radiation Toxicity and Radiation Recall: Administration of ELLENCE after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation (5.10).
- Embryo-Fetal Toxicity: ELLENCE can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. (5.11, 8.1, 8.3).
The most common adverse reactions (≥10%) are leukopenia, neutropenia, anemia, thrombocytopenia, amenorrhea, lethargy, nausea/vomiting, mucositis, diarrhea, infection, conjunctivitis/keratitis, alopecia, local skin 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.
- Avoid using cardiotoxic agents in combination with ELLENCE (7.1).
- Discontinue cimetidine during treatment with ELLENCE (7.2).
USE IN SPECIFIC POPULATIONS
- Lactation: Advise not to breastfeed (8.2).
- Females and Males of Reproductive Potential: May impair fertility (8.3).
See 17 for PATIENT COUNSELING INFORMATION.