TREANDA- bendamustine hydrochloride injection, solution, concentrate
TREANDA- bendamustine hydrochloride injection, powder, lyophilized, for solution
Cephalon, Inc.
1 INDICATIONS AND USAGE
1.1 Chronic Lymphocytic Leukemia (CLL)
TREANDA� 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)
TREANDA 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 TREANDA Formulation to Administer
TREANDA is available in two formulations, a solution (TREANDA Injection) and a lyophilized powder (TREANDA for Injection).
Do not use TREANDA Injection if you intend to use closed system transfer devices (CSTDs), adapters and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS) prior to dilution in the infusion bag [see Dosage and Administration (2.4)].
If using a syringe to withdraw and transfer TREANDA Injection from the vial into the infusion bag, only use a polypropylene syringe with a metal needle and polypropylene hub to withdraw and transfer TREANDA Injection into the infusion bag. Polypropylene syringes are translucent in appearance.
TREANDA Injection and the reconstituted TREANDA 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.
TREANDA Injection must be withdrawn and transferred for dilution in a biosafety cabinet (BSC) or containment isolator using a polypropylene syringe with a metal needle and a polypropylene hub.
If a CSTD or adapter that contains polycarbonate or ABS is used as supplemental protection prior to dilution1 , only use TREANDA for Injection, the lyophilized powder formulation [see How Supplied/Storage and Handling (16.1)].
DOSAGE FORMS AND STRENGTHS
�
TREANDA Injection: 45 mg/0.5 mL or 180 mg/2 mL in a single-dose vial.
�
TREANDA for Injection: 25 mg or 100 mg white to off-white lyophilized powder in a single-dose vial for reconstitution.
4 CONTRAINDICATIONS
TREANDA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine.
DESCRIPTION
Bendamustine hydrochloride is an alkylating agent. The chemical name of bendamustine hydrochloride is 1H-benzimidazole-2-butanoic acid, 5-[bis(2-chloroethyl)amino]-1 methyl-, monohydrochloride. Its empirical molecular formula is C16 H21 Cl2 N3 O2 ∙ HCl, and the molecular weight is 394.7. Bendamustine hydrochloride contains a mechlorethamine group and a benzimidazole heterocyclic ring with a butyric acid substituent
TREANDA Injection (45 mg/0.5 mL or 180 mg/2 mL solution)
TREANDA (bendamustine HCl) Injection is intended for intravenous infusion only after dilution with either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP. It is supplied as a sterile clear colorless to yellow solution in a single-dose vial at the concentration of 90 mg/mL of bendamustine HCl. Each 0.5 mL vial contains 45 mg of bendamustine hydrochloride, 162 mg of Propylene Glycol, USP and 293 mg of N,N-Dimethylacetamide, EP. Each 2 mL vial contains 180 mg of bendamustine hydrochloride, 648 mg of Propylene Glycol, USP and 1172 mg of N,N-Dimethylacetamide, EP. An overfill of 0.2 mL is included in each vial.
TREANDA for Injection (25 mg/vial or 100 mg/vial lyophilized powder)
TREANDA (bendamustine HCl) for Injection is intended for intravenous infusion only after reconstitution with Sterile Water for Injection, USP, and after further dilution with either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP. It is supplied as a sterile non-pyrogenic white to off-white lyophilized powder in a single-dose vial. Each 25-mg vial contains 25 mg of bendamustine hydrochloride and 42.5 mg of mannitol, USP. Each 100-mg vial contains 100 mg of bendamustine hydrochloride and 170 mg of mannitol, USP. The pH of the reconstituted solution is 2.5 - 3.5.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism of action of bendamustine remains unknown.
PATIENT COUNSELING INFORMATION
Allergic (Hypersensitivity) Reactions
Inform patients of the possibility of mild or serious allergic reactions and to immediately report rash, facial swelling, or difficulty breathing during or soon after infusion [see Warnings and Precautions (5.3)].
Myelosuppression
Inform patients of the likelihood that TREANDA will cause a decrease in white blood cells, platelets, and red blood cells, and the need for frequent monitoring of blood counts. Advise patients to report shortness of breath, significant fatigue, bleeding, fever, or other signs of infection [see Warnings and Precautions (5.1)].
Hepatotoxicity
Inform patients of the possibility of developing liver function abnormalities and serious hepatic toxicity. Advise patients to immediately contact their health care provider if signs of liver failure occur, including jaundice, anorexia, bleeding or bruising [see Warnings and Precautions (5.6)].
Fatigue
Advise patients that TREANDA may cause tiredness and to avoid driving any vehicle or operating any dangerous tools or machinery if they experience this side effect [see Adverse Reactions (6.1)].
Nausea and Vomiting
Advise patients that TREANDA may cause nausea and/or vomiting. Patients should report nausea and vomiting so that symptomatic treatment may be provided [see Adverse Reactions (6.1)].
Diarrhea
Advise patients that TREANDA may cause diarrhea. Patients should report diarrhea to the physician so that symptomatic treatment may be provided [see Adverse Reactions (6.1)].
Rash
Advise patients that a rash or itching may occur during treatment with TREANDA. Advise patients to immediately report severe or worsening rash or itching [see Warnings and Precautions (5.5)].
Pregnancy and Nursing
TREANDA can cause fetal harm. Women should be advised to avoid becoming pregnant throughout treatment and for 3 months after TREANDA therapy has stopped. Men receiving TREANDA should use reliable contraception for the same time period. Advise patients to report pregnancy immediately. Advise patients to avoid nursing while receiving TREANDA [see Use in Specific Populations (8.1)].
TRE-013
Distributed By:
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454
TREANDA is a trademark of Cephalon, Inc. or its affiliates.