⛔ FDA Black Box Warning
WARNING: CARDIAC TOXICITY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, and SEVERE MYELOSUPPRESSION • 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/m 2 , 1.6% at 700 mg/m 2 , and 3.3% at 900 mg/m 2 . 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) ] . 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/m 2 , 1.6% at 700 mg/m 2 , and 3.3% at 900 mg/m 2 . 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.
Contraindications
4 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) ] • 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 ).
Pregnancy & Breastfeeding
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 are reports of fetal and/or neonatal cardiotoxicity following in utero exposure to epirubicin (see Clinical Considerations ). In animal reproduction studies in pregnant rats, epirubicin was embryo-fetal lethal and caused structural abnormalities when administered during organogenesis at doses less than the maximum recommended human dose on a body surface area basis ( see Data ). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions There have been rare reports of fetal and/or neonatal transient ventricular hypokinesia, transient elevation of cardiac enzymes, and a case of fetal demise from suspected anthracycline-induced cardiotoxicity following in utero exposure to epirubicin in 2 nd and/or 3 rd trimesters. Cardiotoxicity is a known risk of anthracycline treatment in adults [see Warnings and Precautions (5.1) ]. Monitor the fetus and/or neonate for cardiotoxicity and perform testing consistent with community standards of care. Data Animal Data Intravenous administration of 0.8 mg/kg/day epirubicin (about 0.04 times the maximum recommended single human dose on a body surface area basis) to rats during Days 5 to 15 of gestation resulted in embryofetal lethality (increas