Bendamustine Hydrochloride

BENDAMUSTINE HYDROCHLORIDE- bendamustine hydrochloride injection, powder, lyophilized, for solution
Mylan Institutional LLC

1 INDICATIONS AND USAGE

1.1 Chronic Lymphocytic Leukemia (CLL)

Bendamustine hydrochloride for injection is indicated for the treatment of patients with chronic lymphocytic leukemia. Efficacy relative to first line therapies other than chlorambucil has not been established.

1.2 Non-Hodgkin Lymphoma (NHL)

Bendamustine hydrochloride for injection is indicated for the treatment of patients with indolent B-cell non-Hodgkin lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

2 DOSAGE AND ADMINISTRATION

2.1 Selection of Bendamustine Hydrochloride Formulation to Administer

Bendamustine hydrochloride is available in two formulations, a solution (Bendamustine hydrochloride injection) and a lyophilized powder (Bendamustine hydrochloride for injection).

Bendamustine hydrochloride injection and the reconstituted bendamustine hydrochloride for injection have different concentrations of bendamustine hydrochloride. The concentration of bendamustine hydrochloride in the solution is 90 mg/mL and the concentration of bendamustine hydrochloride in the reconstituted solution of lyophilized powder is 5 mg/mL. Do not mix or combine the two formulations.

If a closed system transfer devices (CSTD) or adapter that contains polycarbonate or acrylonitrile-butadiene-styrene (ABS) is used as supplemental protection prior to dilution1 , only use bendamustine hydrochloride for injection, the lyophilized powder formulation [see How Supplied/Storage and Handling (16.1)].

2.2 Dosing Instructions for CLL

Recommended Dosage:

The recommended dose is 100 mg/m2 administered intravenously over 30 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles.

Dose Delays, Dose Modifications and Reinitiation of Therapy for CLL:

Bendamustine hydrochloride for injection administration should be delayed in the event of Grade 4 hematologic toxicity or clinically significant ≥ Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to ≤ Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) ≥ 1 x 109 /L, platelets ≥ 75 x 109 /L], bendamustine hydrochloride for injection can be reinitiated at the discretion of the treating physician. In addition, dose reduction may be warranted. [see Warnings and Precautions (5.1)]

Dose modifications for hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m2 on Days 1 and 2 of each cycle.

Dose modifications for non-hematologic toxicity: for clinically significant Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle.

Dose re-escalation in subsequent cycles may be considered at the discretion of the treating physician.

2.3 Dosing Instructions for NHL

Recommended Dosage:

The recommended dose is 120 mg/m2 administered intravenously over 60 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles.

Dose Delays, Dose Modifications and Reinitiation of Therapy for NHL:

Bendamustine hydrochloride for injection administration should be delayed in the event of a Grade 4 hematologic toxicity or clinically significant ≥ Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to ≤ Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) ≥ 1 x 109 /L, platelets ≥ 75 x 109 /L], bendamustine hydrochloride for injection can be reinitiated at the discretion of the treating physician. In addition, dose reduction may be warranted. [see Warnings and Precautions (5.1)]

Dose modifications for hematologic toxicity: for Grade 4 toxicity, reduce the dose to 90 mg/m2 on Days 1 and 2 of each cycle; if Grade 4 toxicity recurs, reduce the dose to 60 mg/m2 on Days 1 and 2 of each cycle.

Dose modifications for non-hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 90 mg/m2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m2 on Days 1 and 2 of each cycle.

2.4 Preparation for Intravenous Administration

Bendamustine hydrochloride is a cytotoxic drug. Follow applicable special handling and disposal procedures.1

Bendamustine Hydrochloride for Injection (25 mg/vial or 100 mg/vial lyophilized powder)

If a closed system transfer device or adapter that contains polycarbonate or ABS is to be used as supplemental protection during preparation1 , only use bendamustine hydrochloride for injection, the lyophilized formulation.

Each vial of bendamustine hydrochloride for injection is intended for single dose only.
Aseptically reconstitute each bendamustine hydrochloride for injection vial as follows:
25 mg bendamustine hydrochloride for injection vial: Add 5 mL of only Sterile Water for Injection, USP.
100 mg bendamustine hydrochloride for injection vial: Add 20 mL of only Sterile Water for Injection, USP.
Shake well to yield a clear, colorless to a pale yellow solution with a bendamustine HCl concentration of 5 mg/mL. The lyophilized powder should completely dissolve in 5 minutes. The reconstituted solution must be transferred to the infusion bag within 30 minutes of reconstitution. If particulate matter is observed, the reconstituted product should not be used.
Aseptically withdraw the volume needed for the required dose (based on 5 mg/mL concentration) and immediately transfer to a 500 mL infusion bag of 0.9% Sodium Chloride Injection, USP (normal saline). As an alternative to 0.9% Sodium Chloride Injection, USP (normal saline), a 500 mL infusion bag of 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, may be considered. The resulting final concentration of bendamustine HCl in the infusion bag should be within 0.2 to 0.6 mg/mL. After transferring, thoroughly mix the contents of the infusion bag.
Visually inspect the filled syringe and the prepared infusion bag to ensure the lack of visible particulate matter prior to administration. The admixture should be a clear and colorless to slightly yellow solution.

Use Sterile Water for Injection, USP, for reconstitution and then either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, for dilution, as outlined above. No other diluents have been shown to be compatible.

General Information

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any unused solution should be discarded according to institutional procedures for antineoplastics.

2.5 Admixture Stability

Bendamustine hydrochloride for injection contain no antimicrobial preservative. The admixture should be prepared as close as possible to the time of patient administration.

Bendamustine Hydrochloride for Injection (25 mg/vial or 100 mg/vial lyophilized powder)

Once diluted with either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, the final admixture is stable for 24 hours when stored under refrigerated conditions at 2º to 8°C (36º to 46°F) or for 3 hours when stored at room temperature (15º to 30°C or 59º to 86°F) and room light. Administration of reconstituted and diluted bendamustine hydrochloride for injection must be completed within this period.

3 DOSAGE FORMS AND STRENGTHS

Bendamustine Hydrochloride for Injection: 25 mg or 100 mg white to off-white lyophilized powder in a single-dose vial for reconstitution.

4 CONTRAINDICATIONS

Bendamustine hydrochloride for injection is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine. [see Warnings and Precautions (5.3)]

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