Puridox Injection_

ELLENCE is indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer [see Clinical Studies (14.1) ] . 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 ).

• The recommended starting dose of ELLENCE is 100 to 120 mg/m 2
• Dosage reductions are possible when given in certain combinations . • 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 . • Consider use of antiemetics when given in conjunction with other emetigenic drugs . • Patients administered the 120 mg/m 2 regimen of ELLENCE should receive prophylactic antibiotic therapy . • Adjust dosage after the first treatment cycle based on hematologic and nonhematologic toxicities . • Reduce dose in patients with hepatic impairment . • Consider lower doses in patients with severe renal impairment
• Important Administration Instructions When possible, to reduce the risk of developing cardiotoxicity in patients receiving ELLENCE after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, delay ELLENCE-based therapy until the other agents have cleared from the circulation [see Warnings and Precautions ]
• Antiemetics may reduce nausea and vomiting; consider use of antiemetics before administration of ELLENCE or when clinically indicated, particularly when given in conjunction with other emetigenic drugs [see Adverse Reactions ]
• Patients administered the 120 mg/m 2 regimen of ELLENCE should receive prophylactic antibiotic therapy. …

Injection: 50 mg/25 mL (2 mg/mL), 200 mg/100 mL (2 mg/mL) clear red solution in a single-dose vial. Injection: 50 mg/25 mL (2 mg/mL), 200 mg/100 mL (2 mg/mL) solution in single-dose vials ( 3 ).

• Safety and effectiveness of ELLENCE have not been established
• In pediatric patients
• Pediatric patients may be at greater risk for anthracycline-induced acute manifestations of cardiotoxicity or late cardiovascular dysfunction
• The pharmacokinetics of epirubicin
• In pediatric patients have not been evaluated

Clinical experience in patients who were 65 years of age and older who received ELLENCE chemotherapy regimens for primary breast cancer showed no overall differences in safety and effectiveness compared with younger patients. In elderly female patients, closely monitor for increased toxicity due to the risk of decreased clearance of epirubicin [see Clinical Pharmacology (12.3) ].

• Cardiac Toxicity Inform patients that there is a risk of irreversible myocardial damage associated with treatment with ELLENCE
• Advise patients to immediately contact their healthcare provider or to go to an emergency room for new onset of chest pain, shortness of breath, dizziness, or lightheadedness [see Warnings and Precautions ]
• Secondary Malignancies Inform patients that there is an increased risk of treatment-related leukemia from ELLENCE [see Warnings and Precautions ]
• Extravasation and Tissue Necrosis Inform patients that ELLENCE can cause severe injection site reactions. …

ELLENCE is contraindicated in patients with: • Severe myocardial insufficiency [see Warnings and Precautions (5.1) ] • Recent myocardial infarction or severe arrhythmias, or previous treatment with maximum cumulative dose of anthracyclines [see Warnings and Precautions (5.1) ] • Severe persistent drug-induced myelosuppression [see Warnings and Precautions (5.4) ] • Severe hepatic impairment (defined as Child-Pugh Class C or serum bilirubin level greater than 5 mg/dL) [see Warnings and Precaution …

• Avoid using cardiotoxic agents in combination with ELLENCE ( 7.1 ). • Discontinue cimetidine during treatment with ELLENCE ( 7.2 ). 7.1 Cardiotoxic Agents Closely monitor cardiac function when ELLENCE is used in combination with other cardiotoxic agents. Patients receiving ELLENCE after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may be at an increased risk of developing cardiotoxicity [see Dosage and Administration (2) and Warnings and Precautions (5.1) ] . Trastuzumab may persist in the circulation for up to 7 months. Therefore, avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab when possible. …

• 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 ). …

The following clinically significant adverse reactions are described elsewhere in the labeling: • Cardiac Toxicity [see Warnings and Precautions (5.1) ] • Secondary Malignancies [see Warnings and Precautions (5.2) ] • Extravasation and Tissue Necrosis [see Warnings and Precautions (5.3) ] • Severe Myelosuppression [see Warnings and Precautions (5.4) ] • Tumor-Lysis Syndrome [see Warnings and Precautions (5.7) ] • Thrombophlebitis and Thromboembolic Events [see Warnings and Precautions (5.9) ] • Potentiation of Radiation Toxicity and Radiation Recall [see Warnings and Precautions (5.10) ] The most common adverse reactions (≥10%) are leukopenia, neutropenia, anemia, thrombocytopenia, amenorrhe …

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, ELLENCE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] ; avoid the use of ELLENCE during the 1 st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of epirubicin during the 2 nd and 3 rd trimesters. …

There is no known antidote for overdoses of ELLENCE. A 36-year-old man with non-Hodgkin's lymphoma received a daily 95 mg/m 2 dose of ELLENCE for 5 consecutive days. Five days later, he developed bone marrow aplasia, grade 4 mucositis, and gastrointestinal bleeding. No signs of acute cardiac toxicity were observed. He was treated with antibiotics, colony-stimulating factors, and antifungal agents, and recovered completely. A 63-year-old woman with breast cancer and liver metastasis received a single 320 mg/m 2 dose of ELLENCE. …

Store refrigerated between 2°C and 8°C (36°F and 46°F). Do not freeze. Protect from light. Storage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.