Trade Names:Ellence- Solution for injection 2 mg/mLPharmorubicin PFS (Canada)
Epirubicin is a cell cycle phase, nonspecific anthracycline. It 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.
C max is 5.3 to 9.3 mcg/mL. AUC is 1.6 to 4.2 mcg•h/mL (dose dependent).
Rapidly and widely distributed into tissues. Approximately 77% is protein bound (predominantly albumin).
Extensively and rapidly metabolized by liver and also by other organs and cells, including RBC.
Parent and metabolites eliminated through biliary, and to a lesser extent, urinary. Triphasic elimination with alpha t ½ is approximately 3 min, beta t ½ is 2.5 h, and gamma t ½ is approximately 33 h. Cl is 65 to 83 L/h.
Cl is reduced.
Breast cancer with axillary node involvement.
Small-cell lung cancer, nonsmall-cell lung cancer, Hodgkin lymphoma, non-Hodgkin lymphoma.
Baseline neutrophil count less than 1,500 cells/mm 3 ; severe myocardial insufficiency or recent MI; severe arrhythmias; previous treatment with anthracyclines up to the max cumulative dose; hypersensitivity to epirubicin, other anthracyclines, or anthracenediones; severe hepatic dysfunction.
Epirubicin is given in repeated 3- to 4-wk cycles. The total dose may be given on day 1 of each cycle or divided equally and given on days 1 and 8 of each cycle.Breast Cancer, Combination TherapyAdults
IV Recommended starting dose is 100 to 120 mg/m 2 . Make dosage adjustments after the first treatment cycle based on hematologic and nonhematologic toxicities. Patients experiencing nadir platelet counts less than 50,000/mm 3 , absolute neutrophil counts (ANC) less than 250/mm 3 , neutropenic fever, or grades 3/4 nonhematologic toxicity after the first treatment cycle should have the day 1 dose in subsequent cycles reduced 75% of the day 1 dose given in the current cycle. Delay day 1 chemotherapy in subsequent courses until platelet counts are at least 100,000/mm 3 , ANC at least 1,500/mm 3 , and nonhematologic toxicities have recovered to grade 1 or less. For patients receiving a divided dose (ie, day 1 and day 8), the day 8 dose should be 75% of day 1 if platelet counts are 75,000 to 100,000/mm 3 and ANC is 1,000 to 1,499 mm 3 . If day 8 platelet counts are less than 75,000/mm 3 , ANC less than 1,000/mm 3 , or grade 3/4 nonhematologic toxicity has occurred, omit the day 8 dose.Bone Marrow DysfunctionAdults
IV Consider a lower starting dose (75 to 90 mg/m 2 ) for heavily pretreated patients, patients with preexisting bone marrow depression, or in the presence of neoplastic bone marrow infiltration.Hepatic Dysfunction
Definitive recommendations are not available because patients with hepatic abnormalities were excluded from adjuvant trials. If bilirubin is 1.2 to 3 mg/dL or AST is 2 to 4 ULN, give 1/ 2 of recommended starting dose. If bilirubin is greater than 3 mg/dL or AST is greater than 4 times the ULN, give 1/ 4 of recommended starting dose. Patients with severe hepatic impairment should not receive epirubicin.Renal Dysfunction
Because of limited available data, no specific recommendations can be made; however, consider lower doses in patients with severe renal function impairment (serum creatinine greater than 5 mg/dL).
Store vials in refrigerator (36° to 46°F). Protect from light and freezing. Use within 24 h of first penetration of the rubber stopper. Discard any unused solution. Do not save unused portions for later use.
Cimetidine increases the AUC of epirubicin 50%. Stop cimetidine treatment during treatment with epirubicin.
None well documented.
Adverse reactions listed occurred in patients receiving combination therapy with epirubicin, cyclophosphamide, and fluorouracil.
Delayed dose-related cardiomyopathy; acute arrhythmias. Previous therapy with other anthracyclines may increase risk of cardiotoxicity.
Alopecia (96%); rash; contact dermatitis; urticaria; radiation recall; nail hyperpigmentation.
Moderate to high potential for nausea and vomiting; mucositis within 5 to 10 days of administration; diarrhea.
Dose-limiting bone marrow suppression, leukocyte nadir at 10 to 14 days and recovery by day 21; thrombocytopenia and anemia also may occur with nadirs at 14 to 20 days and 7 to 14 days, respectively.
Acute leukemia and malignant tumors observed.
IV route only. Do not administer via IM or subcutaneous route.Hepatic function impairment
Reduce dose of epirubicin in patients with impaired hepatic function. Evaluate serum total bilirubin and AST levels before and during treatment with epirubicin. Lower doses are recommended in patients with elevated bilirubin or AST. Patients with severe hepatic impairment should not use epirubicin.Extravasation
Local irritation or phlebitis may occur. Severe local tissue necrosis will occur in there is extravasation. Refer to your institution-specific protocol. Monitor IV infusion site for signs or symptoms of extravasation. If noted, immediately discontinue infusion and restart in another vein. Frequently examine extravasation site and immediately inform health care provider if pain, erythema, edema, or vesiculation is noted or if patient reports persistent pain.Myocardial toxicity
May occur either during therapy with epirubicin or months to years after termination of therapy.Secondary, acute, myelogenous leukemia (AML)
AML has been reported in patients with breast cancer treated with anthracyclines, including epirubicin. Secondary leukemia is more common when such drugs are given in combination with DNA-damaging antineoplastic agents when patients have been heavily pretreated with cytotoxic drugs, or when doses of the anthracyclines have been escalated. These leukemias can have a short latency period.Myelosuppression
Severe myelosuppression may occur.
MonitorTotal cumulative dose
Document total cumulative dose. Ensure that dosing beyond 900 mg/m 2 is only attempted after careful evaluation of the patient and clinical situation.
Category D .
Undetermined. Mothers should discontinue nursing prior to taking this drug.
Safety and efficacy in pediatric patients not established.
Reduce dose of epirubicin in patients with renal function impairment. Dosage adjustment is necessary in patients with serum creatinine more than 5 mg/dL.
Evaluate serum total bilirubin and AST levels before and during treatment with epirubicin. Lower doses are recommended in patients with elevated bilirubin or AST. Patients with severe hepatic impairment should not use epirubicin. Specific guidelines are not available for dosage reduction in renal dysfunction.
Discontinue therapy at the first sign of impaired cardiac function and resume therapy only after careful evaluation of the risk vs benefit of continued therapy.
May show on-treatment additive toxicity, especially hematologic and GI effects.
Facial flushing or local erythematous streaking along the vein may be indicative of excessively rapid administration and may precede local phlebitis or thrombophlebitis.
A dose-dependent, reversible leukopenia and/or neutropenia. The WBC nadir is reached 10 to 14 days from drug administration. It is usually transient, returning to normal values by day 21 after drug administration. Severe thrombocytopenia and anemia also may occur. Clinical consequences of severe myelosuppression include fever, infection, septicemia, septic shock, hemorrhage, tissue hypoxia, symptomatic anemia, or death. Monitor patient for signs or symptoms of infection or bleeding. Inform health care provider immediately if noted and be prepared to treat appropriately (eg, IV antibiotics, colony stimulating factors, transfusions).
Evaluate risk of developing hyperuricemia before starting therapy and initiate hypouricemic therapy, including adequate fluid intake, and monitoring of uric acid, before starting treatment in patient determined to be at risk for developing hyperuricemia and urate precipitation.
Ensure that men undergoing epirubicin therapy use effective contraceptive methods.
Previous radiation therapy may induce an inflammatory recall reaction at the site of irradiation.
The occurrence with or without preleukemic phase has been reported in patients treated with anthracyclines.
Thrombophlebitis and thromboembolic phenomenon, including pulmonary embolism, have been reported.
Epirubicin may induce hyperuricemia.
Bone marrow aplasia, grade 4 mucositis, GI bleeding, hyperthermia, multiple organ failure (respiratory and renal), acute lactic acidosis, increased lactate dehydrogenase, anuria, death
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