DOSAGE AND ADMINISTRATION
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:
The 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:
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
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 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).
Definitive 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:
Information regarding experience in patients with hepatic dysfunction is provided in CLINICAL PHARMACOLOGY, Pharmacokinetics In Special Populations.
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).
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 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 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 Injection. Several guidelines on this subject have been published.1 to 8
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 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.
Prolonged 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 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). Epirubicin Hydrochloride Injection should be used within 24 hours of first penetration of the rubber stopper. Discard any unused solution.