Epirubicin Hydrochloride (2 brand names, 2 dosage forms, 2 routes)
Available dosage forms: INJECTABLE, POWDER.
Routes of administration: INJECTION, INTRAVENOUS.
Brand Names
- ELLENCE
- EPIRUBICIN HYDROCHLORIDE
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 [see Warnings and Precautions (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 [see Warnings and Precautions (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 [see Warnings and Precautions (5.3)]. • Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur [see Warnings and Precautions (5.4)].
Indications and Usage
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)].
Contraindications
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 Precautions (5.5)] •Severe hypersensitivity to ELLENCE, other anthracyclines, or anthracenediones [see Adverse Reactions (6.1)]
Adverse Reactions
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)]
Mechanism of Action
Epirubicin is an anthracycline cytotoxic agent. Although it is known that anthracyclines can interfere with a number of biochemical and biological functions within eukaryotic cells, the precise mechanisms of epirubicin’s cytotoxic and/or antiproliferative properties have not been completely elucidated. Epirubicin forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, with consequent inhibition of nucleic acid (DNA and RNA) and protein synthesis. Such intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Epirubicin also inhibits DNA helicase activity, preventing the enzymatic separation of double-stranded DNA and interfering with replication and transcription. Epirubicin is also involved in oxidation/reduction reactions by generating cytotoxic free radicals. The antiproliferative and cytotoxic activity of epirubicin is thought to result from these or other possible mechanisms. Epirubicin is cytotoxic in vitro to a variety of established murine and human cell lines and primary cultures of human tumors. It is also active in vivo against a variety of murine tumors and human xenografts in athymic mice, including breast tumors.
Overdosage
There is no known antidote for overdoses of ELLENCE. A 36-year-old man with non-Hodgkin’s lymphoma received a daily 95 mg/m2 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/m2 dose of ELLENCE. She was hospitalized with hyperthermia and developed multiple organ failure (respiratory and renal), with lactic acidosis, increased lactate dehydrogenase, and anuria. Death occurred within 24 hours after administration of ELLENCE. Additional instances of administration of doses higher than recommended have been reported at doses ranging from 150 to 250 mg/m2. The observed adverse events in these patients were qualitatively similar to known toxicities of epirubicin. Most of the patients recovered with appropriate supportive care. If an overdose occurs, provide supportive treatment (including antibiotic therapy, blood and platelet transfusions, colony-stimulating factors, and intensive care as needed) until the recovery of toxicities. Delayed CHF has been observed months after anthracycline administration. Observe patients carefully over time for signs of CHF and provided with appropriate supportive therapy.