DRUG-DRUG INTERACTIONS
Taxanes. Coadministration of paclitaxel or docetaxel did not affect the pharmacokinetics of epirubicin when given immediately following the taxane. Cimetidine. Coadministration of cimetidine (400 mg twice daily for 7 days starting 5 days before chemotherapy) increased the mean AUC of epirubicin (100 mg/m2) by 50% and decreased its plasma clearance by 30% (see PRECAUTIONS).
Drugs metabolized by cytochrome P-450 enzymes. No systematic in vitro or in vivo evaluation has been performed to examine the potential for inhibition or induction by epirubicin of oxidative cytochrome P-450 isoenzymes.
|
OVERDOSAGE
A 36-year-old man with non-Hodgkin's lymphoma received a daily 95 mg/m2 dose of ELLENCE Injection 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, supportive treatment (including antibiotic therapy, blood and platelet transfusions, colony-stimulating factors, and intensive care as needed) should be provided until the recovery of toxicities. Delayed CHF has been observed months after anthracycline administration. Patients must be observed carefully over time for signs of CHF and provided with appropriate supportive therapy.
|
CONTRAINDICATIONS
Patients should not be treated with ELLENCE Injection if they have any of the following conditions: baseline neutrophil count < 1500 cells/mm3; severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias; previous treatment with anthracyclines up to the maximum cumulative dose; hypersensitivity to epirubicin, other anthracyclines, or anthracenediones; or severe hepaticdysfunction (see WARNINGS and DOSAGE AND ADMINISTRATION).
|
