Ellence Indications, Dosage, Storage, Stability - Epirubicin hydrochloride

Ellence Indications, Dosage, Storage, Stability - Epirubicin hydrochloride

INDICATIONS AND USAGE

ELLENCE Injection is indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer.

ELLENCE Injection is administered to patients by intravenous infusion. ELLENCE is given in repeated 3- to 4-week cycles. The total dose of ELLENCE may be given on Day 1 of each cycle or divided equally and given on Days 1 and 8 of each cycle. The recommended dosages of ELLENCE are as follows:

The recommended starting dose of ELLENCE is 100 to 120 mg/m². The following regimens were used in the trials supporting use of ELLENCE as a component of adjuvant therapy in patients with axillary-node positive breast cancer:

Patients administered the 120-mg/m² regimen of ELLENCE 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 (75-90 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 Dysfunction. Definitive recommendation regarding use of ELLENCE 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 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).

Dosage adjustments after the first treatment cycle should be made based on hematologic and non-hematologic 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 ³100,000/mm³, ANC ³1500/mm³, and nonhematologic toxicities have recovered to ²Grade 1.

For patients receiving a divided dose of ELLENCE (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.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Protective measures. The following protective measures should be taken when handling ELLENCE:

• Personnel should be trained in appropriate techniques for reconstitution and handling.

• Pregnant staff should be excluded from working with this drug.

• Personnel handling ELLENCE 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. ELLENCE should not be mixed with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.

ELLENCE 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.

ELLENCE is provided as a preservative-free, ready-to-use solution.

ELLENCE should be administered into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). The usual infusion time ranges between 3 and 20 minutes depending upon dosage and volume of the infusion solution. 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). ELLENCE should be used within 24 hours of first penetration of the rubber stopper. Discard any unused solution.

ELLENCE Injection is available in polypropylene single-use vials containing 2 mg epirubicin hydrochloride per mL as a sterile, preservative-free, ready-to-use solution in the following strengths: 50 mg/25 mL single-use vial NDC 0009-5091-01 200 mg/100 mL single-use vial NDC 0009-5093-01 Store refrigerated between 2ºC and 8ºC (36ºF and 46ºF). Do not freeze. Protect from light. Discard unused portion.

US Patent No. 5,977,082

Manufactured for: Pharmacia & Upjohn Company, A subsidiary of Pharmacia Corporation, Kalamazoo, MI 49001 USA By: Pharmacia (Perth) Pty Limited, Bentley WA 6102 Australia June 2001 , 817 911 103 692532