Ellence Information
Ellence (Epirubicin hydrochloride)
Ellence (Epirubicin hydrochloride) Indications And Usage
Ellence (Epirubicin hydrochloride) Injection is indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer
Ellence (Epirubicin hydrochloride) Dosage And Administration
When possible, to reduce the risk of developing cardiotoxicity in patients receiving Ellence (Epirubicin hydrochloride) after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, Ellence (Epirubicin hydrochloride) -based therapy should be delayed until the other agents have cleared from the circulation
Administer Ellence (Epirubicin hydrochloride) Injection by intravenous infusion. Give Ellence (Epirubicin hydrochloride) in repeated 3- to 4-week cycles. The total dose of Ellence (Epirubicin hydrochloride) may be given on Day 1 of each cycle or divided equally and given on Days 1 and 8 of each cycle. The recommended dosages of Ellence (Epirubicin hydrochloride) are as follows:
Ellence (Epirubicin hydrochloride) Dosage Forms And Strengths
Ellence (Epirubicin hydrochloride) is provided in polypropylene single-use CYTOSAFE™ vials containing 2 mg epirubicin hydrochloride per mL as a sterile, preservative-free, ready-to-use solution in the following sizes: 50 mg/25 mL and 200 mg/100 mL.
Ellence (Epirubicin hydrochloride) Contraindications
Patients should not be treated with Ellence (Epirubicin hydrochloride) Injection if they have any of the following conditions:
Severe myocardial insufficiency, recent myocardial infarction or severe arrhythmias
Previous treatment with maximum cumulative dose of anthracyclines .
Hypersensitivity to Ellence (Epirubicin hydrochloride) , other anthracyclines, or anthracenediones
Ellence (Epirubicin hydrochloride) Warnings And Precautions
Administer Ellence (Epirubicin hydrochloride) Injection only under the supervision of qualified physicians experienced in the use of cytotoxic therapy. Before beginning treatment with Ellence (Epirubicin hydrochloride) , patients should recover from acute toxicities (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) of prior cytotoxic treatment. Also, precede initial treatment with Ellence (Epirubicin hydrochloride) by a careful baseline assessment of blood counts; serum levels of total bilirubin, AST, and creatinine; and cardiac function as measured by left ventricular ejection function (LVEF). Carefully monitor patients during treatment for possible clinical complications due to myelosuppression. Supportive care may be necessary for the treatment of severe neutropenia and severe infectious complications. Monitoring for potential cardiotoxicity is also important, especially with greater cumulative exposure to Ellence (Epirubicin hydrochloride) .
Ellence (Epirubicin hydrochloride) Injection is administered by intravenous infusion. Venous sclerosis may result from an injection into a small vessel or from repeated injections into the same vein. Extravasation of Ellence (Epirubicin hydrochloride) during the infusion may cause local pain, severe tissue lesions (vesication, severe cellulitis), and necrosis. Administer Ellence (Epirubicin hydrochloride) slowly into the tubing of a freely running intravenous infusion. Patients receiving initial therapy at the recommended starting doses of 100–120 mg/m should generally have Ellence (Epirubicin hydrochloride) infused over 15–20 minutes. For patients who require lower Ellence (Epirubicin hydrochloride) starting doses due to organ dysfunction or who require modification of Ellence (Epirubicin hydrochloride) doses during therapy, the Ellence (Epirubicin hydrochloride) infusion time may be proportionally decreased, but should not be less than 3 minutes. If possible, avoid veins over joints or in extremities with compromised venous or lymphatic drainage. Immediately terminate infusion and restart in another vein if a burning or stinging sensation indicates perivenous infiltration. Perivenous infiltration may occur without causing pain. Facial flushing, as well as local erythematous streaking along the vein, may be indicative of excessively rapid administration. It may precede local phlebitis or thrombophlebitis. Give prophylactic antibiotic therapy to patients administered the 120-mg/m regimen of Ellence (Epirubicin hydrochloride) as a component of combination chemotherapy .
Ellence (Epirubicin hydrochloride) can suppress bone marrow function as manifested by leukopenia, thrombocytopenia and anemia , and myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy .
Cardiotoxicity is a known risk of anthracycline treatment. Anthracycline-induced cardiac toxicity may be manifested by early (or acute) or late (delayed) events. Early cardiac toxicity of Ellence (Epirubicin hydrochloride) consists mainly of sinus tachycardia and/or electrocardiogram (ECG) abnormalities such as non-specific ST-T wave changes, but tachyarrhythmias, including premature ventricular contractions and ventricular tachycardia, bradycardia, as well as atrioventricular and bundle-branch block have also been reported. These effects do not usually predict subsequent development of delayed cardiotoxicity, are rarely of clinical importance, and are generally not considered an indication for the suspension of Ellence (Epirubicin hydrochloride) treatment. Delayed cardiac toxicity results from a characteristic cardiomyopathy that is manifested by reduced LVEF and/or signs and symptoms of congestive heart failure (CHF) such as tachycardia, dyspnea, pulmonary edema, dependent edema, hepatomegaly, ascites, pleural effusion, gallop rhythm. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy. This toxicity appears to be dependent on the cumulative dose of Ellence (Epirubicin hydrochloride) and represents the cumulative dose-limiting toxicity of the drug. If it occurs, delayed cardiotoxicity usually develops late in the course of therapy with Ellence (Epirubicin hydrochloride) or within 2 to 3 months after completion of treatment, but later events (several months to years after treatment termination) have been reported.
Given the risk of cardiomyopathy, exceed a cumulative dose of 900 mg/m Ellence (Epirubicin hydrochloride) only with extreme caution. Risk factors [active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, concomitant use of other drugs with the ability to suppress cardiac contractility or cardiotoxic drugs, especially those with long half-lives (e.g., trastuzumab)] may increase the risk of Ellence (Epirubicin hydrochloride) cardiotoxicity Although not formally tested, it is probable that the toxicity of Ellence (Epirubicin hydrochloride) and other anthracyclines or anthracenediones is additive. Cardiac toxicity with Ellence (Epirubicin hydrochloride) may occur at lower cumulative doses whether or not cardiac risk factors are present.
Although endomyocardial biopsy is recognized as the most sensitive diagnostic tool to detect anthracycline-induced cardiomyopathy, this invasive examination is not practically performed on a routine basis. ECG changes such as dysrhythmias, a reduction of the QRS voltage, or a prolongation beyond normal limits of the systolic time interval may be indicative of anthracycline-induced cardiomyopathy, but ECG is not a sensitive or specific method for following anthracycline-related cardiotoxicity. The risk of serious cardiac impairment may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of Ellence (Epirubicin hydrochloride) at the first sign of impaired function. The preferred method for repeated assessment of cardiac function is evaluation of LVEF measured by multi-gated radionuclide angiography (MUGA) or echocardiography (ECHO). A baseline cardiac evaluation with an ECG and a MUGA scan or an ECHO is recommended, especially in patients with risk factors for increased cardiac toxicity. Perform repeated MUGA or ECHO determinations of LVEF, particularly with higher, cumulative anthracycline doses. The technique used for assessment should be consistent through follow-up. In patients with risk factors, particularly prior anthracycline or anthracenedione use, the monitoring of cardiac function must be particularly strict and the risk-benefit of continuing treatment with Ellence (Epirubicin hydrochloride) in patients with impaired cardiac function must be carefully evaluated.
Do not administer Ellence (Epirubicin hydrochloride) in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored. Patients receiving Ellence (Epirubicin hydrochloride) after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity. Avoid Ellence (Epirubicin hydrochloride) -based therapy for up to 24 weeks after stopping trastuzumab when possible. If Ellence (Epirubicin hydrochloride) is used before this time, monitor cardiac function carefully
The occurrence of secondary acute myelogenous leukemia, with or without a preleukemic phase, has been reported in patients treated with anthracyclines. 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 1- to 3-year latency period. Ellence (Epirubicin hydrochloride) is mutagenic, clastogenic, and carcinogenic in animals
Cimetidine increased the AUC of epirubicin by 50%. Stop Cimetidine treatment during treatment with Ellence (Epirubicin hydrochloride) . ]
Ellence (Epirubicin hydrochloride) can cause fetal harm when administered to a pregnant woman. Epirubicin was embryolethal and teratogenic in rats and rabbits. There are no adequate and well-controlled studies of Ellence (Epirubicin hydrochloride) in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Males with female sexual partners of childbearing potential should use contraception during and after cessation of therapy. may damage testicular tissue and spermatozoa. Possible sperm DNA damage raises concerns about loss of fertility and genetic abnormalities in fetuses. The duration of this effect is uncertain.
Assess blood counts, including absolute neutrophil counts, and liver function before and during each cycle of therapy with Ellence (Epirubicin hydrochloride) . Perform repeated evaluations of LVEF during therapy.
As with other anthracyclines, administration of Ellence (Epirubicin hydrochloride) after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation.
Ellence (Epirubicin hydrochloride) Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Integrated safety data are available from two studies (Studies MA-5 and GFEA-05) evaluating Ellence (Epirubicin hydrochloride) -containing combination regimens in patients with early breast cancer. Of the 1260 patients treated in these studies, 620 patients received the higher-dose Ellence (Epirubicin hydrochloride) regimen (FEC-100/CEF-120), 280 patients received the lower-dose Ellence (Epirubicin hydrochloride) regimen (FEC-50), and 360 patients received CMF. Serotonin-specific antiemetic therapy and colony-stimulating factors were not used in these trials. Clinically relevant acute adverse events are summarized in Table 2.
Ellence (Epirubicin hydrochloride) Drug Interactions
Do not administer Epirubicin in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored. Patients receiving epirubicin after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity. Avoid epirubicin-based therapy for up to 24 weeks after stopping trastuzumab when possible. If epirubicin is used before this time, monitor cardiac function carefully
Concomitant use of Ellence (Epirubicin hydrochloride) with other cardioactive compounds that could cause heart failure (e.g., calcium channel blockers), requires close monitoring of cardiac function throughout treatment.
Cimetidiene increases the exposure to epirubicin Stop Cimetidine during treatment with Ellence (Epirubicin hydrochloride) .
Ellence (Epirubicin hydrochloride) used in combination with other cytotoxic drugs may show on-treatment additive toxicity, especially hematologic and gastrointestinal effects.
There are few data regarding the coadministration of radiation therapy and Ellence (Epirubicin hydrochloride) . In adjuvant trials of Ellence (Epirubicin hydrochloride) -containing CEF-120 or FEC-100 chemotherapies, breast irradiation was delayed until after chemotherapy was completed. This practice resulted in no apparent increase in local breast cancer recurrence relative to published accounts in the literature. A small number of patients received Ellence (Epirubicin hydrochloride) -based chemotherapy concomitantly with radiation therapy but had chemotherapy interrupted in order to avoid potential overlapping toxicities. It is likely that use of Ellence (Epirubicin hydrochloride) with radiotherapy may sensitize tissues to the cytotoxic actions of irradiation. Administration of Ellence (Epirubicin hydrochloride) after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation.
Epirubicin is extensively metabolized by the liver. Changes in hepatic function induced by concomitant therapies may affect epirubicin metabolism, pharmacokinetics, therapeutic efficacy, and/or toxicity.
Ellence (Epirubicin hydrochloride) Overdosage
There is no known antidote for overdoses of Ellence (Epirubicin hydrochloride) . A 36-year-old man with non-Hodgkin's lymphoma received a daily 95 mg/m dose of Ellence (Epirubicin hydrochloride) 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/m dose of Ellence (Epirubicin hydrochloride) . 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 (Epirubicin hydrochloride) . Additional instances of administration of doses higher than recommended have been reported at doses ranging from 150 to 250 mg/m. 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.
Ellence (Epirubicin hydrochloride) Description
Ellence (Epirubicin hydrochloride) Injection (epirubicin hydrochloride injection) is an anthracycline cytotoxic agent, intended for intravenous administration. Ellence (Epirubicin hydrochloride) is supplied as a sterile, clear, red solution and is available in polypropylene vials containing 50 and 200 mg of epirubicin hydrochloride as a preservative-free, ready-to-use solution. Each milliliter of solution contains 2 mg of epirubicin hydrochloride. Inactive ingredients include sodium chloride, USP, and water for injection, USP. The pH of the solution has been adjusted to 3.0 with hydrochloric acid, NF.
Epirubicin hydrochloride is the 4-epimer of doxorubicin and is a semi-synthetic derivative of daunorubicin. The chemical name is (8S-)-10-[(3-amino-2,3,6-trideoxy-α-L- -hexopyranosyl)oxy]-7,8,9,10-tetrahydro6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione hydrochloride. The active ingredient is a red-orange hygroscopic powder, with the empirical formula CHNO HCl and a molecular weight of 579.95. The structural formula is as follows:
Ellence (Epirubicin hydrochloride) Clinical Pharmacology
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.
Ellence (Epirubicin hydrochloride) Clinical Studies
Ellence (Epirubicin hydrochloride) How Supplied/storage And Handling
Ellence (Epirubicin hydrochloride) Injection is available in polypropylene single-use CYTOSAFE™ vials containing 2 mg epirubicin hydrochloride per mL as a sterile, preservative-free, ready-to-use solution in the following strengths:
Ellence (Epirubicin hydrochloride) Patient Counseling Information
Inform patients of the expected adverse effects of Ellence (Epirubicin hydrochloride) , including gastrointestinal symptoms (nausea, vomiting, diarrhea, and stomatitis), alopecia and potential neutropenic complications.
Patients should understand that there is a risk of irreversible myocardial damage associated with treatment with Ellence (Epirubicin hydrochloride) , as well as a risk of treatment-related leukemia.
Patients should consult their physician if vomiting, dehydration, fever, evidence of infection, symptoms of CHF, or injection-site pain occurs following therapy with Ellence (Epirubicin hydrochloride) .
Advise patients that their urine may appear red for 1 to 2 days after administration of Ellence (Epirubicin hydrochloride) and that they should not be alarmed.
Because Ellence (Epirubicin hydrochloride) may induce chromosomal damage in sperm, advise men undergoing treatment with Ellence (Epirubicin hydrochloride) to use effective contraceptive methods. Women treated with Ellence (Epirubicin hydrochloride) may develop irreversible amenorrhea, or premature menopause.
Ellence (Epirubicin hydrochloride)
Ellence (Epirubicin hydrochloride)
Ellence (Epirubicin hydrochloride)
