Epirubicin Hydrochloride
Loading...Epirubicin Hydrochloride Recall
Get an alert when a recall is issued.
Questions & Answers
Side Effects & Adverse Reactions
Epirubicin Hydrochloride Injection should be administered only under the supervision of qualified physicians experienced in the use of cytotoxic therapy. Before beginning treatment with epirubicin, patients should recover from acute toxicities (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) of prior cytotoxic treatment. Also, initial treatment with Epirubicin Hydrochloride Injection should be preceded 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). Patients should be carefully monitored 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 epirubicin.
A dose-dependent, reversible leukopenia and/or neutropenia is the predominant manifestation of hematologic toxicity associated with epirubicin and represents the most common acute dose-limiting toxicity of this drug. In most cases, the white blood cell (WBC) nadir is reached 10 to 14 days from drug administration. Leukopenia/neutropenia is usually transient, with WBC and neutrophil counts generally returning to normal values by Day 21 after drug administration. As with other cytotoxic agents, Epirubicin Hydrochloride Injection at the recommended dose in combination with cyclophosphamide and fluorouracil can produce severe leukopenia and neutropenia. Severe thrombocytopenia and anemia may also occur. Clinical consequences of severe myelosuppression include fever, infection, septicemia, septic shock, hemorrhage, tissue hypoxia, symptomatic anemia, or death. If myelosuppressive complications occur, appropriate supportive measures (e.g., intravenous antibiotics, colony-stimulating factors, transfusions) may be required. Myelosuppression requires careful monitoring. Total and differential WBC, red blood cell (RBC), and platelet counts should be assessed before and during each cycle of therapy with Epirubicin Hydrochloride Injection.
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 epirubicin consists mainly of sinus tachycardia and/or 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 epirubicin 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 Epirubicin Hydrochloride Injection and represents the cumulative dose-limiting toxicity of the drug. If it occurs, delayed cardiotoxicity usually develops late in the course of therapy with Epirubicin Hydrochloride Injection or within 2 to 3 months after completion of treatment, but later events (several months to years after treatment termination) have been reported.
In a retrospective survey, including 9144 patients, mostly with solid tumors in advanced stages, the probability of developing CHF increased with increasing cumulative doses of Epirubicin Hydrochloride Injection (Figure 5). The estimated risk of epirubicin-treated patients developing clinically evident CHF was 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 developing CHF in the absence of other cardiac risk factors increased steeply after an epirubicin cumulative dose of 900 mg/m2.
In another retrospective survey of 469 epirubicin-treated patients with metastatic or early breast cancer, the reported risk of CHF was comparable to that observed in the larger study of over 9000 patients.
Given the risk of cardiomyopathy, a cumulative dose of 900 mg/m2 Epirubicin Hydrochloride Injection should be exceeded 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) may increase the risk of cardiac toxicity. Although not formally tested, it is probable that the toxicity of epirubicin and other anthracyclines or anthracenediones is additive. Cardiac toxicity with Epirubicin Hydrochloride Injection 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. Electrocardiogram (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 Epirubicin Hydrochloride Injection 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. Repeated MUGA or ECHO determinations of LVEF should be performed, 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 Epirubicin Hydrochloride Injection in patients with impaired cardiac function must be carefully evaluated.
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. An analysis of 7110 patients who received adjuvant treatment with epirubicin in controlled clinical trials as a component of poly-chemotherapy regimens for early breast cancer, showed a cumulative risk of secondary acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS) of about 0.27% (approximate 95% CI, 0.14 to 0.40) at 3 years, 0.46% (approximate 95% CI, 0.28 to 0.65) at 5 years and 0.55% (approximate 95% CI, 0.33 to 0.78) at 8 years. The risk of developing AML/MDS increased with increasing epirubicin cumulative doses as shown in Figure 6.
The cumulative probability of developing AML/MDS was found to be particularly increased in patients who received more than the maximum recommended cumulative dose of epirubicin (720 mg/m2) or cyclophosphamide (6,300 mg/m2), as shown in Table 4.
| Years from Treatment start | Cumulative Probability of Developing AML/MDS % (95% CI) | |||
|---|---|---|---|---|
| Cyclophosphamide Cumulative Dose ≤6,300 mg/m2 | Cyclophosphamide Cumulative Dose >6,300 mg/m2 | |||
| Epirubicin Cumulative Dose | Epirubicin Cumulative Dose | Epirubicin Cumulative Dose | Epirubicin Cumulative Dose | |
| ≤720 mg/m2 | >720 mg/m2 | ≤720 mg/m2 | >720 mg/m2 | |
| N=4760 | N=111 | N=890 | N=261 | |
| 3 | 0.12 (0.01 to 0.22) | 0.00 (0.00 to 0.00) | 0.12 (0.00 to 0.37) | 4.37 (1.69 to 7.05) |
| 5 | 0.25 (0.08 to 0.42) | 2.38 (0.00 to 6.99) | 0.31 (0.00 to 0.75) | 4.97 (2.06 to 7.87) |
| 8 | 0.37 (0.13 to 0.61) | 2.38 (0.00 to 6.99) | 0.31 (0.00 to 0.75) | 4.97 (2.06 to 7.87) |
Epirubicin Hydrochloride Injection is mutagenic, clastogenic, and carcinogenic in animals (see next section, Carcinogenesis, Mutagenesis & Impairment of Fertility).
Treatment-related acute myelogenous leukemia has been reported in women treated with epirubicin-based adjuvant chemotherapy regimens (see above section, WARNINGS, Secondary Leukemia). Conventional long-term animal studies to evaluate the carcinogenic potential of epirubicin have not been conducted, but intravenous administration of a single 3.6 mg/kg epirubicin dose to female rats (about 0.2 times the maximum recommended human dose on a body surface area basis) approximately doubled the incidence of mammary tumors (primarily fibroadenomas) observed at 1 year. Administration of 0.5 mg/kg epirubicin intravenously to rats (about 0.025 times the maximum recommended human dose on a body surface area basis) every 3 weeks for ten doses increased the incidence of subcutaneous fibromas in males over an 18-month observation period. In addition, subcutaneous administration of 0.75 or 1.0 mg/kg/day (about 0.015 times the maximum recommended human dose on a body surface area basis) to newborn rats for 4 days on both the first and tenth day after birth for a total of eight doses increased the incidence of animals with tumors compared to controls during a 24-month observation period.
Epirubicin was mutagenic in vitro to bacteria (Ames test) either in the presence or absence of metabolic activation and to mammalian cells (HGPRT assay in V79 Chinese hamster lung fibroblasts) in the absence but not in the presence of metabolic activation. Epirubicin was clastogenic in vitro (chromosome aberrations in human lymphocytes) both in the presence and absence of metabolic activation and was also clastogenic in vivo (chromosome aberration in mouse bone marrow).
In fertility studies in rats, males were given epirubicin daily for 9 weeks and mated with females that were given epirubicin daily for 2 weeks prior to mating and through Day 7 of gestation. When 0.3 mg/kg/day (about 0.015 times the maximum recommended human single dose on a body surface area basis) was administered to both sexes, no pregnancies resulted. No effects on mating behavior or fertility were observed at 0.1 mg/kg/day, but male rats had atrophy of the testes and epididymis, and reduced spermatogenesis. The 0.1 mg/kg/day dose also caused embryolethality. An increased incidence of fetal growth retardation was observed in these studies at 0.03 mg/kg/day (about 0.0015 times the maximum recommended human single dose on a body surface area basis). Multiple daily doses of epirubicin to rabbits and dogs also caused atrophy of male reproductive organs. Single 20.5 and 12 mg/kg doses of intravenous epirubicin caused testicular atrophy in mice and rats, respectively (both approximately 0.5 times the maximum recommended human dose on a body surface area basis). A single dose of 16.7 mg/kg epirubicin caused uterine atrophy in rats.
Although experimental data are not available, Epirubicin Hydrochloride Injection could induce chromosomal damage in human spermatozoa due to its genotoxic potential. Men undergoing treatment with Epirubicin Hydrochloride Injection should use effective contraceptive methods. Epirubicin Hydrochloride Injection may cause irreversible amenorrhea (premature menopause) in premenopausal women.
The major route of elimination of epirubicin is the hepatobiliary system (see CLINICAL PHARMACOLOGY, Pharmacokinetics in Special Populations). Serum total bilirubin and AST levels should be evaluated before and during treatment with Epirubicin Hydrochloride Injection. Patients with elevated bilirubin or AST may experience slower clearance of drug with an increase in overall toxicity. Lower doses are recommended in these patients (see DOSAGE AND ADMINISTRATION). Patients with severe hepatic impairment have not been evaluated; therefore, epirubicin should not be used in this patient population.
Serum creatinine should be assessed before and during therapy. Dosage adjustment is necessary in patients with serum creatinine >5 mg/dL (see DOSAGE AND ADMINISTRATION). Patients undergoing dialysis have not been studied.
As with other cytotoxic agents, Epirubicin Hydrochloride Injection may induce hyperuricemia as a consequence of the extensive purine catabolism that accompanies drug-induced rapid lysis of highly chemosensitive neoplastic cells (tumor lysis syndrome). Other metabolic abnormalities may also occur. While not generally a problem in patients with breast cancer, physicians should consider the potential for tumor-lysis syndrome in potentially susceptible patients and should consider monitoring serum uric acid, potassium, calcium, phosphate, and creatinine immediately after initial chemotherapy administration. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor-lysis syndrome.
Epirubicin Hydrochloride Injection may cause fetal harm when administered to a pregnant woman. Administration of 0.8 mg/kg/day intravenously of epirubicin to rats (about 0.04 times the maximum recommended single human dose on a body surface area basis) during Days 5 to 15 of gestation was embryotoxic (increased resorptions and post-implantation loss) and caused fetal growth retardation (decreased body weight), but was not teratogenic up to this dose. Administration of 2 mg/kg/day intravenously of epirubicin to rats (about 0.1 times the maximum recommended single human dose on a body surface area basis) on Days 9 and 10 of gestation was embryotoxic (increased late resorptions, post-implantation losses, and dead fetuses; and decreased live fetuses), retarded fetal growth (decreased body weight), and caused decreased placental weight. This dose was also teratogenic, causing numerous external (anal atresia, misshapen tail, abnormal genital tubercle), visceral (primarily gastrointestinal, urinary, and cardiovascular systems), and skeletal (deformed long bones and girdles, rib abnormalities, irregular spinal ossification) malformations. Administration of intravenous epirubicin to rabbits at doses up to 0.2 mg/kg/day (about 0.02 times the maximum recommended single human dose on a body surface area basis) during Days 6 to 18 of gestation was not embryotoxic or teratogenic, but a maternally toxic dose of 0.32 mg/kg/day increased abortions and delayed ossification. Administration of a maternally toxic intravenous dose of 1 mg/kg/day epirubicin to rabbits (about 0.1 times the maximum recommended single human dose on a body surface area basis) on Days 10 to 12 of gestation induced abortion, but no other signs of embryofetal toxicity or teratogenicity were observed. When doses up to 0.5 mg/kg/day epirubicin were administered to rat dams from Day 17 of gestation to Day 21 after delivery (about 0.025 times the maximum recommended single human dose on a body surface area basis), no permanent changes were observed in the development, functional activity, behavior, or reproductive performance of the offspring.
There are no adequate and well-controlled studies in pregnant women. Two pregnancies have been reported in women taking epirubicin. A 34-year-old woman, 28 weeks pregnant at her diagnosis of breast cancer, was treated with cyclophosphamide and epirubicin every 3 weeks for 3 cycles. She received the last dose at 34 weeks of pregnancy and delivered a healthy baby at 35 weeks. A second 34-year-old woman with breast cancer metastatic to the liver was randomized to FEC-50 but was removed from study because of pregnancy. She experienced a spontaneous abortion. If epirubicin is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
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.
History
There is currently no drug history available for this drug.
Other Information
Epirubicin Hydrochloride Injection is an anthracycline cytotoxic agent, intended for intravenous administration. Epirubicin Hydrochloride Injection is supplied as a sterile, clear, red solution and is available in glass 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- cis)-10-[(3-amino-2,3,6-trideoxy-α-L- arabino-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 C27 H29 NO11 HCl and a molecular weight of 579.95. The structural formula is as follows:
NH2∙HCl
Sources
Epirubicin Hydrochloride Manufacturers
-
Generamedix, Inc.
![Epirubicin Hydrochloride (Epirubicin Hydrochloride) Injection, Solution [Generamedix, Inc.]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Epirubicin Hydrochloride | Generamedix, Inc.
Epirubicin Hydrochloride Injection is administered to patients by intravenous infusion. Epirubicin Hydrochloride Injection is given in repeated 3- to 4-week cycles. The total dose of Epirubicin Hydrochloride Injection 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 Epirubicin Hydrochloride Injection are as follows:
Starting DosesThe recommended starting dose of Epirubicin Hydrochloride Injection is 100 to 120 mg/m2. The following regimens were used in the trials supporting use of Epirubicin Hydrochloride Injection as a component of adjuvant therapy in patients with axillary-node positive breast cancer:
CEF-120:
Cyclophosphamide 75 mg/m2 PO D 1 to 14
Epirubicin Hydrochloride Injection 60 mg/m2 IV D 1, 8
5-Fluorouracil 500 mg/m2 IV D 1, 8
Repeated every 28 days for 6 cycles
FEC-100:
5-Fluorouracil 500 mg/m2
Epirubicin Hydrochloride Injection 100 mg/m2
Cyclophosphamide 500 mg/m2
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120-mg/m2 regimen of Epirubicin Hydrochloride Injection also received prophylactic antibiotic therapy with trimethoprim-sulfamethoxazole (e.g., Septra® Bactrim™) or a fluoroquinolone.
* Spectra® is a registered trademark of Monarch Pharmaceuticals, Inc.
* Bactrim™ is a trademark of AR Scientific.
Bone Marrow DysfunctionConsideration should be given to administration of lower starting doses (75 to 90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration (see WARNINGS and PRECAUTIONS).
Hepatic DysfunctionDefinitive recommendations regarding use of Epirubicin Hydrochloride Injection in patients with hepatic dysfunction are not available because patients with hepatic abnormalities were excluded from participation in adjuvant trials of FEC-100/CEF-120 therapy. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions were recommended in clinical trials, although few patients experienced hepatic impairment:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose
Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting dose
Information regarding experience in patients with hepatic dysfunction is provided in CLINICAL PHARMACOLOGY, Pharmacokinetics In Special Populations.
Renal DysfunctionWhile no specific dose recommendation can be made based on the limited available data in patients with renal impairment, lower doses should be considered in patients with severe renal impairment (serum creatinine > 5 mg/dL).
Dose ModificationsDosage adjustments after the first treatment cycle should be made based on hematologic and nonhematologic toxicities. Patients experiencing during treatment cycle nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3 or 4 nonhematologic toxicity should have the Day 1 dose in subsequent cycles reduced to 75% of the Day 1 dose given in the current cycle. Day 1 chemotherapy in subsequent courses of treatment should be delayed until platelet counts are ≥ 100,000/mm3, ANC ≥ 1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1. For patients receiving a divided dose of Epirubicin Hydrochloride Injection(Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000 to 100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grade 3 or 4 nonhematologic toxicity has occurred, the Day 8 dose should be omitted.
Preparation & Administration PrecautionsParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures normally used for proper handling and disposal of anticancer drugs should be considered for use with Epirubicin Hydrochloride Injection. Several guidelines on this subject have been published.1 to 8
Protective measuresThe following protective measures should be taken when handling Epirubicin Hydrochloride Injection:
Personnel should be trained in appropriate techniques for reconstitution and handling.
Pregnant staff should be excluded from working with this drug.
Personnel handling Epirubicin Hydrochloride Injection should wear protective clothing: goggles, gowns and disposable gloves and masks.
A designated area should be defined for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper.
All items used for reconstitution, administration or cleaning (including gloves) should be placed in high-risk, waste-disposal bags for high temperature incineration.
Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All contaminated and cleaning materials should be placed in high-risk, waste-disposal bags for incineration. Accidental contact with the skin or eyes should be treated immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Medical attention should be sought. Always wash hands after removing gloves.
IncompatibilitiesProlonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drug. Epirubicin Hydrochloride Injection should not be mixed with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin Hydrochloride Injection can be used in combination with other antitumor agents, but it is not recommended that it be mixed with other drugs in the same syringe.
Preparation of Infusion SolutionEpirubicin Hydrochloride Injection is provided as a preservative-free, ready-to-use solution.
Epirubicin Hydrochloride Injection should be administered into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100 to 120 mg/m2should generally have epirubicin infused over 15 to 20 minutes. For patients who require lower epirubicin starting doses due to organ dysfunction or who require modification of epirubicin doses during therapy, the epirubicin infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein (see PRECAUTIONS). Epirubicin Hydrochloride Injection should be used within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Otn Generics Inc.
Epirubicin Hydrochloride | Otn Generics Inc.
Epirubicin Injection is administered to patients by intravenous infusion. Epirubicin is given in repeated 3- to 4-week cycles. The total dose of Epirubicin Hydrochloride Injection 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 epirubicin are as follows:
Starting DosesThe recommended starting dose of epirubicin is 100 to 120 mg/m2. The following regimens were used in the trials supporting use of epirubicin as a component of adjuvant therapy in patients with axillary-node positive breast cancer:
CEF-120: Cyclophosphamide
epirubicin
5-Fluorouracil
Repeated every 28 days for 6 cycles 75 mg/m2 PO D 1–14
60 mg/m2 IV D 1, 8
500 mg/m2 IV D 1, 8 FEC-100: 5-Fluorouracil
epirubicin
Cyclophosphamide 500 mg/m2
100 mg/m2
500 mg/m2 All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cyclesPatients administered the 120-mg/m2 regimen of epirubicin also received prophylactic antibiotic therapy with trimethoprim-sulfamethoxazole (e.g., Septra®, Bactrim®) or a fluoroquinolone.
Bone Marrow DysfunctionConsideration should be given to administration of lower starting doses (75–90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration (see WARNINGS and PRECAUTIONS).
Hepatic DysfunctionDefinitive recommendations regarding use of epirubicin in patients with hepatic dysfunction are not available because patients with hepatic abnormalities were excluded from participation in adjuvant trials of FEC-100/CEF-120 therapy. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions were recommended in clinical trials, although few patients experienced hepatic impairment:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseInformation regarding experience in patients with hepatic dysfunction is provided in CLINICAL PHARMACOLOGY, Pharmacokinetics In Special Populations.
Renal DysfunctionWhile no specific dose recommendation can be made based on the limited available data in patients with renal impairment, lower doses should be considered in patients with severe renal impairment (serum creatinine > 5 mg/dL).
Dose ModificationsDosage adjustments after the first treatment cycle should be made based on hematologic and nonhematologic toxicities. Patients experiencing during treatment cycle nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity should have the Day 1 dose in subsequent cycles reduced to 75% of the Day 1 dose given in the current cycle. Day 1 chemotherapy in subsequent courses of treatment should be delayed until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
For patients receiving a divided dose of epirubicin (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000–100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grade 3/4 nonhematologic toxicity has occurred, the Day 8 dose should be omitted.
Preparation & Administration PrecautionsParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures normally used for proper handling and disposal of anticancer drugs should be considered for use with epirubicin. Several guidelines on this subject have been published.1–8
Protective measuresThe following protective measures should be taken when handling epirubicin:
Personnel should be trained in appropriate techniques for reconstitution and handling. Pregnant staff should be excluded from working with this drug. Personnel handling epirubicin should wear protective clothing: goggles, gowns and disposable gloves and masks. A designated area should be defined for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. All items used for reconstitution, administration or cleaning (including gloves) should be placed in high-risk, waste-disposal bags for high temperature incineration. Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All contaminated and cleaning materials should be placed in high-risk, waste-disposal bags for incineration. Accidental contact with the skin or eyes should be treated immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Medical attention should be sought. Always wash hands after removing gloves. IncompatibilitiesProlonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drug. epirubicin should not be mixed with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin can be used in combination with other antitumor agents, but it is not recommended that it be mixed with other drugs in the same syringe.
Preparation of Infusion SolutionEpirubicin is provided as a preservative-free, ready-to-use solution.
Epirubicin should be administered into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100–120 mg/m2 should generally have epirubicin infused over 15–20 minutes. For patients who require lower epirubicin starting doses due to organ dysfunction or who require modification of epirubicin doses during therapy, the epirubicin infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein (see PRECAUTIONS). Epirubicin should be used within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
App Pharmaceuticals, Llc
Epirubicin Hydrochloride | App Pharmaceuticals, Llc
Epirubicin hydrochloride injection is administered to patients by intravenous infusion. Epirubicin hydrochloride injection is given in repeated 3-4 week cycles. The total dose of 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 epirubicin hydrochloride are as follows:
Starting Doses
The recommended starting dose of epirubicin hyrochloride injection is 100 to 120 mg/m 2. The following regimens were used in the trials supporting use of epirubicin hyrochloride injection as a component of adjuvant therapy in patients with axillary-node positive breast cancer:
CEF-120:
Cyclophosphamide
75 mg/m2 PO D 1 to 14
Epirubicin Hydrochloride
60 mg/m2 I.V. D 1, 8
5-Fluorouracil
500 mg/m2 I.V. D 1, 8
Repeated every 28 days for 6 cycles
FEC-100:
5-Fluorouracil
500 mg/m2
Epirubicin Hydrochloride
100 mg/m2
Cyclophosphamide
500 mg/m2
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120 mg/m 2 regimen of epirubicin hydrochloride also received prophylactic antibiotic therapy with trimethoprim-sulfamethoxazole (e.g., Septra ®, Bactrim ®) or a fluoroquinolone.Bone Marrow Dysfunction. Consideration should be given to administration of lower starting doses (75 to 90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration (see WARNINGS and PRECAUTIONS sections).
Hepatic Dysfunction. Definitive recommendations regarding use of epirubicin hydrochloride in patients with hepatic dysfunction are not available because patients with hepatic abnormalities were excluded from participation in adjuvant trials of FEC-100/CEF-120 therapy. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions were recommended in clinical trials, although few patients experienced hepatic impairment:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose Bilirubin >3 mg/dL or AST >4 times upper limit of normal 1/4 of recommended starting doseInformation regarding experience in patients with hepatic dysfunction is provided in CLINICAL PHARMACOLOGY, Pharmacokinetics In Special Populations section.
Renal Dysfunction. While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, lower doses should be considered in patients with severe renal impairment (serum creatinine >5 mg/dL).
Dose Modifications
Dosage adjustments after the first treatment cycle should be made based on hematologic and nonhematologic toxicities. Patients experiencing during treatment cycle nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity should have the Day 1 dose in subsequent cycles reduced to 75% of the Day 1 dose given in the current cycle. Day 1 chemotherapy in subsequent courses of treatment should be delayed until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤Grade 1.
For patients receiving a divided dose of epirubicin hydrochloride (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000 to 100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grade 3/4 nonhematologic toxicity has occurred, the Day 8 dose should be omitted.
Preparation & Administration Precautions
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures normally used for proper handling and disposal of anticancer drugs should be considered for use with epirubicin hydrochloride. Several guidelines on this subject have been published.1-8
Protective measures. The following protective measures should be taken when handling epirubicin hydrochloride injection:
Personnel should be trained in appropriate techniques for reconstitution and handling. Pregnant staff should be excluded from working with this drug. Personnel handling epirubicin hydrochloride should wear protective clothing: goggles, gowns and disposable gloves and masks. A designated area should be defined for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. All items used for reconstitution, administration or cleaning (including gloves) should be placed in high-risk, waste-disposal bags for high temperature incineration.Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All contaminated and cleaning materials should be placed in high-risk, waste-disposal bags for incineration. Accidental contact with the skin or eyes should be treated immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Medical attention should be sought. Always wash hands after removing gloves.
Incompatibilities. Prolonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drug. Epirubicin hydrochloride should not be mixed with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin hydrochloride can be used in combination with other antitumor agents, but it is not recommended that it be mixed with other drugs in the same syringe.
Preparation of Infusion Solution
Epirubicin hydrochloride injection is provided as a preservative-free, ready-to-use solution.
Epirubicin hydrochloride injection should be administered into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100 to 120 mg/m2should generally have epirubicin infused over 15 to 20 minutes. For patients who require lower epirubicin starting doses due to organ dysfunction or who require modification of epirubicin doses during therapy, the epirubicin infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein (see PRECAUTIONS section). Epirubicin hydrochloride injection should be used within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Greenstone, Llc
Epirubicin Hydrochloride | Greenstone, Llc
When possible, to reduce the risk of developing cardiotoxicity in patients receiving Epirubicin HCl after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, Epirubicin HCl-based therapy should be delayed until the other agents have cleared from the circulation [see Warnings and Precautions (5.3)].
Administer Epirubicin HCl Injection by intravenous infusion. Give Epirubicin HCl in repeated 3- to 4-week cycles. The total dose of Epirubicin HCl 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 Epirubicin HCl are as follows:
2.1 Recommended DoseThe recommended dose of Epirubicin HCl is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120: Cyclophosphamide 75 mg/m2 PO D 1–14 Epirubicin HCl 60 mg/m2 IV D 1, 8 5-Fluorouracil 500 mg/m2 IV D 1, 8 Repeated every 28 days for 6 cycles FEC-100: 5-Fluorouracil 500 mg/m2 Epirubicin HCl 100 mg/m2 Cyclophosphamide 500 mg/m2 All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cyclesPatients administered the 120-mg/m2 regimen of Epirubicin HCl should receive prophylactic antibiotic therapy.
2.2 Dose ModificationsEpirubicin HCl dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce Epirubicin HCl Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75–90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of Epirubicin HCl (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000–100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of Epirubicin HCl in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseRenal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine > 5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15–25ºC).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing Epirubicin HCl. Several guidelines on this subject have been published.1–4 [see References (15)].
Protective Measures
Take the following protective measures when handling Epirubicin HCl:
Train personnel in appropriate techniques for reconstitution and handling. Exclude pregnant staff from working with this drug. Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling Epirubicin HCl. Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix Epirubicin HCl with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin HCl can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer Epirubicin HCl into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100–120 mg/m2 should generally have Epirubicin HCl infused over 15–20 minutes. For patients who require lower Epirubicin HCl starting doses due to organ dysfunction or who require modification of Epirubicin HCl doses during therapy, the Epirubicin HCl infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use Epirubicin HCl within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Areva Pharmaceuticals,inc.
Epirubicin Hydrochloride | Areva Pharmaceuticals,inc.
When possible, to reduce the risk of developing cardiotoxicity in patients receiving EPIRUBICIN HYDROCHLORIDE after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, EPIRUBICIN HYDROCHLORIDE-based therapy should be delayed until the other agents have cleared from the circulation [see Warnings and Precautions (5.3)]. Administer EPIRUBICIN HYDROCHLORIDE Injection by intravenous infusion. Give EPIRUBICIN HYDROCHLORIDE in repeated 3- to 4-week cycles. The total dose of 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 EPIRUBICIN HYDROCHLORIDE are as follows:
2.1 Recommended DoseThe recommended dose of EPIRUBICIN HYDROCHLORIDE is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120: Cyclophosphamide 750mg/m2 PO D 1-14
EPIRUBICIN HYDROCHLROIDE 60 mg/m2 IV D 1, 8
5-Fluorouracil 500 mg/m2 IV D 1, 8
Repeated every 28 days for 6 cycles
FEC-100: 5-Fluorouracil 500 mg/m2
EPIRUBICIN HYDROCHLROIDE 100 mg/m2
Cylcophosphamide 500mg/m2
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120-mg/m2 regimen of EPIRUBICIN HYDROCHLORIDE should receive prophylactic antibiotic therapy.
2.2 Dose ModificationsEPIRUBICIN HYDROCHLORIDE dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce EPIRUBICIN HYDROCHLORIDE Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75-90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of EPIRUBICIN HYDROCHLORIDE (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000-100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of EPIRUBICIN HYDROCHLORIDE in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
• Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose
• Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting dose
Renal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine > 5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15-25ºC).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing EPIRUBICIN HYDROCHLORIDE. Several guidelines on this subject have been published.1-4[see References (15)].
Protective Measures
Take the following protective measures when handling EPIRUBICIN HYDROCHLORIDE: Train personnel in appropriate techniques for reconstitution and handling. Exclude pregnant staff from working with this drug. Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling EPIRUBICIN HYDROCHLORIDE. Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix EPIRUBICIN HYDROCHLORIDE with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation. EPIRUBICIN HYDROCHLORIDE can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer EPIRUBICIN HYDROCHLORIDE into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100-120 mg/m2 should generally have EPIRUBICIN HYDROCHLORIDE infused over 15-20 minutes. For patients who require lower EPIRUBICIN HYDROCHLORIDE starting doses due to organ dysfunction or who require modification of EPIRUBICIN HYDROCHLORIDE doses during therapy, the EPIRUBICIN HYDROCHLORIDE infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use EPIRUBICIN HYDROCHLORIDE within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Teva Parenteral Medicines, Inc.
Epirubicin Hydrochloride | Teva Parenteral Medicines, Inc.
When possible, to reduce the risk of developing cardiotoxicity in patients receiving epirubicin hydrochloride injection after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, epirubicin hydrochloride injection-based therapy should be delayed until the other agents have cleared from the circulation [see Warnings and Precautions (5.3)].
Administer epirubicin hydrochloride injection by intravenous infusion. Give epirubicin hydrochloride injection in repeated 3 to 4 week cycles. The total dose of epirubicin hydrochloride injection 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 epirubicin hydrochloride injection are as follows:
2.1 Recommended DoseThe recommended dose of epirubicin hydrochloride injection is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120:
Cyclophosphamide
75 mg/m2 PO D 1 to 14
Epirubicin Hydrochloride Injection
60 mg/m2 IV D 1, 8
5-Fluorouracil
500 mg/m2 IV D 1, 8
Repeated every 28 days for 6 cycles
FEC-100:
5-Fluorouracil
500 mg/m2
Epirubicin Hydrochloride Injection
100 mg/m2
Cyclophosphamide
500 mg/m2
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
2.2 Dose Modifications
Patients administered the 120 mg/m2 regimen of epirubicin hydrochloride injection should receive prophylactic antibiotic therapy.Epirubicin hydrochloride injection dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts < 50,000/mm3, absolute neutrophil counts (ANC) < 250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce epirubicin hydrochloride injection Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥ 100,000/mm3, ANC ≥ 1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75 to 90 mg/m2) for heavily pretreated patients, patients with preexisting bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of epirubicin hydrochloride injection (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000 to 100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are < 75,000/mm3, ANC < 1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of epirubicin hydrochloride injection in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
• Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose • Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseRenal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine > 5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15 to 25°C).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing epirubicin hydrochloride injection. Several guidelines on this subject have been published1-4 [see References (15)].
Protective Measures
Take the following protective measures when handling epirubicin hydrochloride injection:
• Train personnel in appropriate techniques for reconstitution and handling. • Exclude pregnant staff from working with this drug. • Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling epirubicin hydrochloride injection. • Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. • Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. • Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix epirubicin hydrochloride injection with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin hydrochloride injection can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer epirubicin hydrochloride injection into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100 to 120 mg/m2 should generally have epirubicin hydrochloride injection infused over 15 to 20 minutes. For patients who require lower epirubicin hydrochloride injection starting doses due to organ dysfunction or who require modification of epirubicin hydrochloride injection doses during therapy, the epirubicin hydrochloride injection infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use epirubicin hydrochloride injection within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Amneal-agila, Llc
Epirubicin Hydrochloride | Amneal-agila, Llc
When possible, to reduce the risk of developing cardiotoxicity in patients receiving Epirubicin Hydrochloride Injection after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, Epirubicin Hydrochloride Injection-based therapy should be delayed until the other agents have cleared from the circulation [see Warnings and Precautions (5.3)].
Administer Epirubicin Hydrochloride Injection by intravenous infusion. Give Epirubicin Hydrochloride Injection in repeated 3- to 4-week cycles. The total dose of Epirubicin Hydrochloride Injection 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 Epirubicin Hydrochloride Injection are as follows:
2.1 Recommended DoseThe recommended dose of Epirubicin Hydrochloride Injection is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120: Cyclophosphamide 75 mg/m2 PO D 1-14 Epirubicin Hydrochloride Injection 60 mg/m2 IV D 1, 8 5-Fluorouracil 500 mg/m2IV D 1, 8 Repeated every 28 days for 6 cycles FEC-100: 5-Fluorouracil 500 mg/m2 Epirubicin Hydrochloride Injection 100 mg/m2 Cyclophosphamide 500 mg/m2 All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cyclesPatients administered the 120-mg/m2 regimen of Epirubicin Hydrochloride Injection should receive prophylactic antibiotic therapy.
2.2 Dose ModificationsEpirubicin Hydrochloride Injection dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce Epirubicin Hydrochloride Injection Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75 to 90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of Epirubicin Hydrochloride Injection (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000 to 100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of Epirubicin Hydrochloride Injection in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseRenal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine > 5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15º to 25ºC).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing Epirubicin Hydrochloride Injection. Several guidelines on this subject have been published.1-4 [see References (15)].
Protective Measures
Take the following protective measures when handling Epirubicin Hydrochloride Injection:
Train personnel in appropriate techniques for reconstitution and handling. Exclude pregnant staff from working with this drug. Wear protective clothing: goggles, gowns and disposable gloves and masks when handling Epirubicin Hydrochloride Injection. Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix Epirubicin Hydrochloride Injection with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin Hydrochloride Injection can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer Epirubicin Hydrochloride Injection into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100 to 120 mg/m2 should generally have Epirubicin Hydrochloride Injection infused over 15 to 20 minutes. For patients who require lower Epirubicin Hydrochloride Injection starting doses due to organ dysfunction or who require modification of Epirubicin Hydrochloride Injection doses during therapy, the Epirubicin Hydrochloride Injection infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use Epirubicin Hydrochloride Injection within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Hospira Worldwide, Inc.
Epirubicin Hydrochloride | Hospira Worldwide, Inc.
When possible, to reduce the risk of developing cardiotoxicity in patients receiving Epirubicin Hydrochloride Injection after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, Epirubicin Hydrochloride Injection-based therapy should be delayed until the other agents have cleared from the circulation [see Warnings and Precautions (5.3)].
Administer Epirubicin Hydrochloride Injection by intravenous infusion. Give Epirubicin Hydrochloride Injection in repeated 3- to 4-week cycles. The total dose of Epirubicin Hydrochloride Injection 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 Epirubicin Hydrochloride Injection are as follows:
2.1 Recommended DoseThe recommended dose of Epirubicin Hydrochloride Injection is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120:
Cyclophosphamide
75 mg/m2 PO D 1-14
Epirubicin Hydrochloride Injection
60 mg/m2 IV D 1, 8
5-Fluorouracil
500 mg/m2 IV D 1, 8
Repeated every 28 days for 6 cycles
FEC-100:
5-Fluorouracil
500 mg/m2
Epirubicin Hydrochloride Injection
100 mg/m2
Cyclophosphamide
500 mg/m2
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120-mg/m2 regimen of Epirubicin Hydrochloride Injection should receive prophylactic antibiotic therapy.
2.2 Dose ModificationsEpirubicin Hydrochloride Injection dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce Epirubicin Hydrochloride Injection Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75-90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of Epirubicin Hydrochloride Injection (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000-100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of Epirubicin Hydrochloride Injection in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
• Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose • Bilirubin >3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseRenal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine >5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15-25°C).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing Epirubicin Hydrochloride Injection. Several guidelines on this subject have been published.1-4 [See References (15).]
Protective Measures
Take the following protective measures when handling Epirubicin Hydrochloride Injection:
• Train personnel in appropriate techniques for reconstitution and handling. • Exclude pregnant staff from working with this drug. • Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling Epirubicin Hydrochloride Injection. • Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. • Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. • Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix Epirubicin Hydrochloride Injection with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin Hydrochloride Injection can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer Epirubicin Hydrochloride Injection into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100-120 mg/m2 should generally have Epirubicin Hydrochloride Injection infused over 15-20 minutes. For patients who require lower Epirubicin Hydrochloride Injection starting doses due to organ dysfunction or who require modification of Epirubicin Hydrochloride Injection doses during therapy, the Epirubicin Hydrochloride Injection infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use Epirubicin Hydrochloride Injection within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
2.1 Recommended DoseThe recommended dose of Epirubicin Hydrochloride Injection is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120:
Cyclophosphamide
75 mg/m2 PO D 1-14
Epirubicin Hydrochloride Injection
60 mg/m2 IV D 1, 8
5-Fluorouracil
500 mg/m2 IV D 1, 8
Repeated every 28 days for 6 cycles
FEC-100:
5-Fluorouracil
500 mg/m2
Epirubicin Hydrochloride Injection
100 mg/m2
Cyclophosphamide
500 mg/m2
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120-mg/m2 regimen of Epirubicin Hydrochloride Injection should receive prophylactic antibiotic therapy.
2.2 Dose ModificationsEpirubicin Hydrochloride Injection dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce Epirubicin Hydrochloride Injection Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75-90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of Epirubicin Hydrochloride Injection (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000-100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of Epirubicin Hydrochloride Injection in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
• Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose • Bilirubin >3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseRenal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine >5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15-25°C).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing Epirubicin Hydrochloride Injection. Several guidelines on this subject have been published.1-4 [See References (15).]
Protective Measures
Take the following protective measures when handling Epirubicin Hydrochloride Injection:
• Train personnel in appropriate techniques for reconstitution and handling. • Exclude pregnant staff from working with this drug. • Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling Epirubicin Hydrochloride Injection. • Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. • Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. • Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix Epirubicin Hydrochloride Injection with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin Hydrochloride Injection can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer Epirubicin Hydrochloride Injection into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100-120 mg/m2 should generally have Epirubicin Hydrochloride Injection infused over 15-20 minutes. For patients who require lower Epirubicin Hydrochloride Injection starting doses due to organ dysfunction or who require modification of Epirubicin Hydrochloride Injection doses during therapy, the Epirubicin Hydrochloride Injection infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use Epirubicin Hydrochloride Injection within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Sandoz Inc
Epirubicin Hydrochloride | Sandoz Inc
When possible, to reduce the risk of developing cardiotoxicity in patients receiving epirubicin hydrochloride injection after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, epirubicin hydrochloride injection-based therapy should be delayed until the other agents have cleared from the circulation [see WARNINGS AND PRECAUTIONS (5.3)]. Administer epirubicin hydrochloride injection by intravenous infusion. Give epirubicin hydrochloride injection in repeated 3- to 4-week cycles. The total dose of epirubicin hydrochloride injection 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 epirubicin hydrochloride injection are as follows:
2.1 Recommended DoseThe recommended dose of epirubicin hydrochloride injection is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120:
Cyclophosphamide
75 mg/m2 PO D 1 to 14
Epirubicin hydrochloride injection
60 mg/m2 IV D 1,8
5-Fluorouracil
500 mg/m2 IV D 1,8
Repeated every 28 days for 6 cycles
FEC-100:
5-Fluorouracil
500 mg/m2
Epirubicin hydrochloride injection
100 mg/m2
Cyclophosphamide
500 mg/m2
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120-mg/m2 regimen of epirubicin hydrochloride injection should receive prophylactic antibiotic therapy.
2.2 Dose ModificationsEpirubicin hydrochloride injection dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce epirubicin hydrochloride injection Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75 to 90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see WARNINGS AND PRECAUTIONS (5)]. For patients receiving a divided dose of epirubicin hydrochloride injection (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000 to 100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of epirubicin hydrochloride injection in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see WARNINGS AND PRECAUTIONS (5.5) and CLINICAL PHARMACOLOGY (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
• Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose • Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseRenal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine > 5 mg/dL) [see WARNINGS AND PRECAUTIONS (5.6) and CLINICAL PHARMACOLOGY (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15 to 25ºC).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing epirubicin hydrochloride injection. Several guidelines on this subject have been published.1-4 [see REFERENCES (15)].
Protective Measures
Take the following protective measures when handling epirubicin hydrochloride injection:
• Train personnel in appropriate techniques for reconstitution and handling. • Exclude pregnant staff from working with this drug. • Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling epirubicin hydrochloride injection. • Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. • Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. • Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix epirubicin hydrochloride injection with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin hydrochloride injection can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer epirubicin hydrochloride injection into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100 to 120 mg/m2 should generally have epirubicin hydrochloride injection infused over 15 to 20 minutes. For patients who require lower epirubicin hydrochloride injection starting doses due to organ dysfunction or who require modification of epirubicin hydrochloride injection doses during therapy, the epirubicin hydrochloride injection infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see WARNINGS AND PRECAUTIONS (5.9)]. Use epirubicin hydrochloride injection within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Mylan Institutional Llc
Epirubicin Hydrochloride | Mylan Institutional Llc
When possible, to reduce the risk of developing cardiotoxicity in patients receiving Epirubicin Hydrochloride Injection after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, Epirubicin Hydrochloride Injection -based therapy should be delayed until the other agents have cleared from the circulation [see Warnings and Precautions (5.3)].
Administer Epirubicin Hydrochloride Injection by intravenous infusion. Give Epirubicin Hydrochloride Injection in repeated 3- to 4-week cycles. The total dose of Epirubicin Hydrochloride Injection 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 Epirubicin Hydrochloride Injection are as follows:
2.1 Recommended DoseThe recommended dose of Epirubicin Hydrochloride Injection is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120:
Cyclophosphamide
75 mg/m2 PO D 1-14
Epirubicin Hydrochloride Injection
60 mg/m2 IV D 1, 8
5-Fluorouracil
500 mg/m2 IV D 1, 8
Repeated every 28 days for 6 cycles
FEC-100:
5-Fluorouracil
500 mg/m2
Epirubicin Hydrochloride Injection
100 mg/m2
Cyclophosphamide
500 mg/m2
All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120-mg/m2 regimen of Epirubicin Hydrochloride Injection should receive prophylactic antibiotic therapy.
2.2 Dose ModificationsEpirubicin Hydrochloride Injection dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce Epirubicin Hydrochloride Injection Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75-90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of Epirubicin Hydrochloride Injection (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000-100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of Epirubicin Hydrochloride Injection in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseRenal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine > 5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15° to 25°C).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing Epirubicin Hydrochloride Injection. Several guidelines on this subject have been published.1-4 [see References (15)].
Protective Measures
Take the following protective measures when handling Epirubicin Hydrochloride Injection:
Train personnel in appropriate techniques for reconstitution and handling. Exclude pregnant staff from working with this drug. Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling Epirubicin Hydrochloride Injection. Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix Epirubicin Hydrochloride Injection with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.
Epirubicin Hydrochloride Injection can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer Epirubicin Hydrochloride Injection into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100 to 120 mg/m2 should generally have Epirubicin Hydrochloride Injection infused over 15 to 20 minutes. For patients who require lower Epirubicin Hydrochloride Injection starting doses due to organ dysfunction or who require modification of Epirubicin Hydrochloride Injection doses during therapy, the Epirubicin Hydrochloride Injection infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use Epirubicin Hydrochloride Injection within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
-
Sagent Pharmaceuticals
Epirubicin Hydrochloride | Sagent Pharmaceuticals
When possible, to reduce the risk of developing cardiotoxicity in patients receiving epirubicin hydrochloride injection after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, epirubicin hydrochloride injection-based therapy should be delayed until the other agents have cleared from the circulation [see Warnings and Precautions (5.3)].
Administer epirubicin hydrochloride injection by intravenous infusion. Give epirubicin hydrochloride injection in repeated 3- to 4-week cycles. The total dose of epirubicin hydrochloride injection 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 epirubicin hydrochloride injection are as follows:
2.1 Recommended DoseThe recommended dose of epirubicin hydrochloride injection is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120: Cyclophosphamide
Epirubicin hydrochloride injection
5-Fluorouracil
Repeated every 28 days for 6 cycles 75 mg/m2 PO D 1-14
60 mg/m2 IV D 1, 8
500 mg/m2 IV D 1, 8
FEC-100: 5-Fluorouracil
Epirubicin hydrochloride injection
Cyclophosphamide 500 mg/m2
100 mg/m2
500 mg/m2All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120-mg/m2 regimen of epirubicin hydrochloride injection should receive prophylactic antibiotic therapy.
2.2 Dose ModificationsEpirubicin hydrochloride injection dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce epirubicin hydrochloride injection Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.
Bone Marrow Dysfunction
Consider administering a lower starting dose (75-90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of epirubicin hydrochloride injection (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000-100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.
Hepatic Impairment
Recommendations regarding use of epirubicin hydrochloride injection in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting doseRenal Impairment
While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine > 5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].
2.3 Preparation and Administration PrecautionsStorage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15-25ºC).
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing epirubicin hydrochloride injection. Several guidelines on this subject have been published.1-4 [see References (15)].
Protective Measures
Take the following protective measures when handling epirubicin hydrochloride injection:
Train personnel in appropriate techniques for reconstitution and handling. Exclude pregnant staff from working with this drug. Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling epirubicin hydrochloride injection. Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.Incompatibilities
Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix epirubicin hydrochloride injection with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation. Epirubicin hydrochloride injection can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.
Preparation of Infusion Solution
Administer epirubicin hydrochloride injection into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100-120 mg/m2 should generally have epirubicin hydrochloride injection infused over 15-20 minutes. For patients who require lower epirubicin hydrochloride injection starting doses due to organ dysfunction or who require modification of epirubicin hydrochloride injection doses during therapy, the epirubicin hydrochloride injection infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use epirubicin hydrochloride injection within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
![Epirubicin Hydrochloride Injection, Solution [Greenstone, Llc]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=bc0a3a39-4ac3-47de-a388-9c3672e3e130&name=epirubicin-09.jpg)
![Epirubicin Hydrochloride Injection [Areva Pharmaceuticals,inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=ab115cc4-43cd-4a59-aa01-89e356ce3a08&name=epirubicininjection-figure-02.jpg)
![Epirubicin Hydrochloride Injection, Solution [Teva Parenteral Medicines, Inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=f91fc962-7c70-46a9-81fe-b98e93a2028a&name=image-08.jpg)
![Epirubicin Hydrochloride Injection [Amneal-agila, Llc]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=062a2a13-d9b6-4b35-9d8d-febdd2f6cac3&name=epirubicin-hcl-injection-10.jpg)
![Epirubicin Hydrochloride Injection, Solution [Hospira Worldwide, Inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=573eefd9-3f28-4053-a8ed-1fb531c38e15&name=epirubicin-hydrochloride-injection3-figure-8-j482743.jpg)
![Epirubicin Hydrochloride Injection, Solution [Sandoz Inc]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=140e953d-d180-4097-80da-b3ecb50465d5&name=516afd6b-38ec-4819-9bb1-37606c0d6739-08.jpg)
![Epirubicin Hydrochloride Injection [Mylan Institutional Llc ]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=3b59118b-7645-46b1-b3ed-3e72b2bf270c&name=epirubicin-inj-mylan-figure-08.jpg)
![Epirubicin Hydrochloride Injection [Sagent Pharmaceuticals]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=f9a93841-f097-472a-b4a5-ee7a2aa74164&name=epi03-0007-08.jpg)
Login To Your Free Account