BENDEKA- bendamustine hydrochloride injection, solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

BENDAMUSTINE HYDROCHLORIDE (UNII: 981Y8SX18M) (BENDAMUSTINE - UNII:9266D9P3PQ)

Available from:

Teva Pharmaceuticals USA, Inc.

INN (International Name):

bendamustine hydrochloride

Composition:

bendamustine hydrochloride 25 mg in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

BENDEKA® is indicated for the treatment of patients with chronic lymphocytic leukemia. Efficacy relative to first line therapies other than chlorambucil has not been established. BENDEKA 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. BENDEKA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine, polyethylene glycol 400, propylene glycol, or monothioglycerol. [see Warnings and Precautions (5.4)] Risk Summary In animal reproduction studies, intraperitoneal administration of bendamustine to pregnant mice and rats during organogenesis at doses 0.6 to 1.8 times the maximum recommended human dose (MRHD) resulted in embryo-fetal and/or infant mortality, structural abnormalities, and alterations to growth (see Data) . There are no available data on bendamustine hydrochloride use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Bendamustine hydrochloride was intraperitoneally administered once to mice from 210 mg/m2 (approximately 1.8 times the MRHD) during organogenesis and caused an increase in resorptions, skeletal and visceral malformations (exencephaly, cleft palates, accessory rib, and spinal deformities) and decreased fetal body weights. This dose did not appear to be maternally toxic and lower doses were not evaluated. Repeat intraperitoneal administration of bendamustine hydrochloride to mice on gestation days 7 to 11 resulted in an increase in resorptions from 75 mg/m2 (approximately 0.6 times the MRHD) and an increase in abnormalities from 112.5 mg/m2 (approximately 0.9 times the MRHD), similar to those seen after a single intraperitoneal administration. Bendamustine hydrochloride was intraperitoneally administered once to rats from 120 mg/m2 (approximately the MRHD) on gestation days 4, 7, 9, 11, or 13 and caused embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses. A significant increase in external (effect on tail, head, and herniation of external organs [exomphalos]) and internal (hydronephrosis and hydrocephalus) malformations were seen in dosed rats. Risk Summary There are no data on the presence of bendamustine hydrochloride or its metabolites in either human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with BENDEKA, and for 1 week after the last dose. BENDEKA can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiation of BENDEKA [see Use in Specific Populations (8.1)] . Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with BENDEKA and for 6 months after the last dose. Males Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with BENDEKA and for 3 months after the last dose [see Nonclinical Toxicology (13.1)] . Infertility Males Based on findings from clinical studies, BENDEKA may impair male fertility. Impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in male patients treated with alkylating agents, especially in combination with other drugs. In some instances, spermatogenesis may return in patients in remission, but this may occur only several years after intensive chemotherapy has been discontinued. Advise patients of the potential risk to their reproductive capacities. Based on findings from animal studies, BENDEKA may impair male fertility due to an increase in morphologically abnormal spermatozoa. The long-term effects of BENDEKA on male fertility, including the reversibility of adverse effects, have not been studied [see Nonclinical Toxicology (13.1)] . Safety and effectiveness in pediatric patients have not been established. Safety, pharmacokinetics and efficacy were assessed in a single open-label trial (NCT01088984) in patients aged 1 to 19 years with relapsed or refractory acute leukemia, including 27 patients with acute lymphocytic leukemia (ALL) and 16 patients with acute myeloid leukemia (AML). Bendamustine hydrochloride was administered as an intravenous infusion over 60 minutes on Days 1 and 2 of each 21-day cycle. There was no treatment response (CR+ CRp) in any patient. The safety profile in these patients was consistent with that seen in adults, and no new safety signals were identified. The pharmacokinetics of bendamustine in 43 patients, aged 1 to 19 years (median age of 10 years) were within range of values previously observed in adults given the same dose based on body surface area. No overall differences in safety were observed between patients ≥65 years of age and younger patients. Efficacy was lower in patients 65 and over with CLL receiving bendamustine hydrochloride based upon an overall response rate of 47% for patients 65 and over and 70% for younger patients. Progression free survival was also longer in younger patients with CLL receiving bendamustine (19 months vs. 12 months). No overall differences in efficacy in patients with non-Hodgkin Lymphoma were observed between geriatric patients and younger patients. Do not use BENDEKA in patients with creatinine clearance (CLcr) < 30 mL/min [see Clinical Pharmacology (12.3)] . Do not use BENDEKA in patients with AST or ALT 2.5-10 × upper limit of normal (ULN) and total bilirubin 1.5-3 × ULN, or total bilirubin > 3 × ULN [see Clinical Pharmacology (12.3)] .

Product summary:

Safe Handling and Disposal BENDEKA (bendamustine hydrochloride) injection is a hazardous drug. Follow applicable special handling and disposal procedures.1 Care should be exercised in the handling and preparation of solutions prepared from BENDEKA (bendamustine hydrochloride) injection. The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If a solution of BENDEKA (bendamustine hydrochloride) injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If BENDEKA (bendamustine hydrochloride) injection contacts the mucous membranes, flush thoroughly with water. How Supplied BENDEKA (bendamustine hydrochloride) injection is supplied in individual cartons of 5 mL clear multiple-dose vials containing 100 mg of bendamustine hydrochloride as a clear, and colorless to yellow ready-to-dilute solution. Storage Store BENDEKA (bendamustine hydrochloride) injection in refrigerator, 2°C to 8°C (36°F to 46°F). Retain in original carton until time of use to protect from light.

Authorization status:

New Drug Application

Summary of Product characteristics

BENDEKA- BENDAMUSTINE HYDROCHLORIDE INJECTION, SOLUTION
TEVA PHARMACEUTICALS USA, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
BENDEKA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR BENDEKA.
BENDEKA (BENDAMUSTINE HYDROCHLORIDE INJECTION), FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2008
INDICATIONS AND USAGE
BENDEKA injection is an alkylating drug indicated for treatment of
patients with:
Chronic lymphocytic leukemia (CLL). Efficacy relative to first line
therapies other than chlorambucil has
not been established. (1.1)
Indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during
or within six months of
treatment with rituximab or a rituximab-containing regimen. (1.2)
DOSAGE AND ADMINISTRATION
For CLL:
100 mg/m infused intravenously over 10 minutes on Days 1 and 2 of a
28-day cycle, up to 6 cycles.
(2.1)
For NHL:
120 mg/m infused intravenously over 10 minutes on Days 1 and 2 of a
21-day cycle, up to 8 cycles.
(2.2)
DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/4 mL (25 mg/mL) in a multiple-dose vial. (3)
CONTRAINDICATIONS
BENDEKA is contraindicated in patients with a history of a
hypersensitivity reaction to bendamustine,
polyethylene glycol 400, propylene glycol, or monothioglycerol.
Reactions to bendamustine hydrochloride
have included anaphylaxis and anaphylactoid reactions (4, 5.4)
WARNINGS AND PRECAUTIONS
Myelosuppression: Delay or reduce dose, and restart treatment based on
ANC and platelet count
recovery. (2.1, 5.1)
Infections: Monitor for fever and other signs of infection or
reactivation of infections and treat promptly.
(5.2)
Progressive multifocal leukoencephalopathy (PML): Monitor for new or
worsening neurological, cognitive
or behavioral signs or symptoms suggestive of PML. (5.3)
Anaphylaxis and Infusion Reactions: Severe anaphylactic reactions have
occurred. Monitor clinically and
discontinue drug for severe reactions. Pre-medicate in subsequent
cycles for milder reactions. (5.4)
Tumor Lysis Syndrome: May