Vivimusta (bendamustine HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Bendamustine, a bifunctional nitrogen mustard-derivative alkylating agent and purine analog, is an antineoplastic agent.
Bendamustine, a bifunctional nitrogen mustard-derivative alkylating agent and purine analog, is an antineoplastic agent. Bendamustine is structurally related to chlorambucil, with the molecules differing only in the central ring structure; whereas chlorambucil contains a benzene ring, bendamustine contains a purine-like benzimidazole ring.
The exact mechanism(s) of action of bendamustine has not been conclusively established. As an alkylating agent, bendamustine interferes with DNA replication and transcription of RNA, ultimately resulting in disruption of nucleic acid function. In vitro data suggest that bendamustine activates different DNA repair pathways compared with conventional alkylating agents.
In addition, other effects of bendamustine may contribute to its antineoplastic activity, including induction of p53-dependent genes that activate apoptosis and inhibition of several mitotic checkpoints. As a consequence of the latter effect, DNA-damaged cells entering the M phase of the cell cycle may undergo a premature form of necrotic cell death known as mitotic catastrophe. The drug is active against both quiescent and dividing cells.
Cross-resistance between bendamustine and other alkylating agents or fludarabine appears to be incomplete.
Following IV infusion of bendamustine hydrochloride over 10 minutes (Bendeka(R)) or over 60 minutes (Treanda(R)), systemic exposure to the drug is equivalent although peak plasma concentrations are higher following the shorter infusion. Bendamustine is metabolized extensively by hydrolysis, oxidation, and conjugation. In vitro data indicate that bendamustine is metabolized mainly via hydrolysis to form 2 metabolites with low cytotoxic activity, monohydroxybendamustine (HP1) and dihydroxybendamustine (HP2), and to a lesser extent via cytochrome P-450 (CYP) isoenzyme 1A2 to form 2 active metabolites, gamma-hydroxybendamustine (M3) and N-desmethylbendamustine (M4).
However, because plasma concentrations of gamma-hydroxybendamustine and N-desmethylbendamustine are only 10 and 1%, respectively, that of the parent drug, the cytotoxic activity of bendamustine appears to result mainly from the parent drug. Following administration of radiolabeled bendamustine hydrochloride, plasma radioactivity levels were more sustained than plasma concentrations of the drug and its active metabolites, suggesting the presence of bendamustine-derived compounds with longer half-lives. Approximately 50% of the radiolabeled dose was recovered in urine (approximately 3.3% of the dose as unchanged drug, less than 6% as the dihydroxy, gamma-hydroxy, and N-desmethyl metabolites) and 25% was recovered in feces.
Following IV administration of bendamustine hydrochloride as a single 120-mg/m2 dose over 1 hour, the intermediate half-life of the parent drug was approximately 40 minutes. Little or no accumulation of bendamustine in plasma is expected when the drug is administered on days 1 and 2 of a 28-day treatment cycle.
USES: This medication is used to treat certain types of cancer. Bendamustine belongs to a class of cancer chemotherapy drugs known as alkylating agents. It works by killing cancer cells or slowing their growth.
Generic name: bendamustine HCl
Pronunciation: (BEN-da-MUS-teen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Vivimusta
Indications
The following indications are listed for Vivimusta:
- Chronic Lymphoid Leukemia
- Follicular Lymphoma
- Indolent B-Cell Non-Hodgkin Lymphoma
- Small Lymphocytic Lymphoma
Also known as: Follicular B-Cell Lymphoma, Follicular B-Cell Non-Hodgkin's Lymphoma, Indolent B-Cell Nhl.
Dosing
Appropriate measures (e.g., adequate hydration) should be taken during therapy to prevent hyperuricemia. (See Tumor Lysis Syndrome under Cautions.)
Although measures to prevent infusion reactions are not routinely recommended by the manufacturer prior to the initial dose of bendamustine, a premedication regimen (e.g., antihistamine, antipyretic, and corticosteroid) should be considered during subsequent treatment cycles in patients who have experienced grade 1 or 2 infusion reactions to the drug. Bendamustine should be discontinued in patients who experience grade 4 infusion reactions. Discontinuance of bendamustine therapy should be considered in patients who experience grade 3 infusion reactions. (See Infusion Reactions under Cautions.)
Bendamustine hydrochloride is commercially available as an injection concentrate (Bendeka(R), Belrapzo(R)) and as a lyophilized powder (Treanda(R)). The injection concentrate formulation of Treanda(R) has been discontinued by the manufacturer because of incompatibility with devices, adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS).
Treanda(R) and Belrapzo(R) are administered by IV infusion over 30 minutes in patients with chronic lymphocytic leukemia (CLL) or over 60 minutes in patients with rituximab-refractory, indolent, B-cell non-Hodgkin's lymphoma (NHL). Bendeka(R) is administered by IV infusion over 10 minutes in patients with either CLL or rituximab-refractory, indolent, B-cell NHL. Care should be taken to avoid extravasation of the drug. (See Local Effects under Cautions.)
Appropriate measures (e.g., adequate hydration) should be taken during therapy to prevent tumor lysis syndrome. Although allopurinol has been used during the initiation of bendamustine therapy to prevent hyperuricemia, concomitant use of these drugs may increase the risk of severe skin reactions. (See Dermatologic Reactions under Cautions.)
In patients who have experienced grade 1 or 2 infusion reactions to the drug, a premedication regimen (e.g., antihistamine, antipyretic, and corticosteroid) should be considered during subsequent treatment cycles. (See Dosage under Dosage and Administration.)
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known history of hypersensitivity (e.g., anaphylactic or anaphylactoid reaction) to bendamustine or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 15% or more of patients with rituximab-refractory, indolent, B-cell NHL or with CLL receiving bendamustine therapy include neutropenia, thrombocytopenia, anemia, leukopenia, pyrexia, nausea, vomiting, hyperbilirubinemia, and lymphopenia. Elevated bilirubin concentrations also have been reported in more than 15% of patients with CLL receiving the drug, and fatigue, diarrhea, constipation, decreased weight, anorexia, dyspnea, cough, headache, rash, and stomatitis also have been reported in 15% or more of patients with rituximab-refractory, indolent, B-cell NHL receiving the drug. Adverse effects reported in more than 5% of patients during or within 24 hours post-infusion include nausea and fatigue.
Adverse effects are similar following administration of bendamustine as a 10-minute IV infusion (Bendeka(R)) or following IV infusion over 30-60 minutes (Treanda(R)).
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Pharmacokinetic and adverse effect profiles of bendamustine in pediatric patients (1-19 years of age) with relapsed or refractory acute leukemia are similar to those in adults.
Efficacy of bendamustine has not been established in pediatric patients. Bendamustine hydrochloride (90 or 120 mg/m2 IV daily on days 1 and 2 of each 21-day cycle) was evaluated in a phase 1-2 study in pediatric patients with relapsed or refractory acute leukemia. No responses were observed in 32 patients evaluated in the phase 2 portion of the study; however, complete responses were observed in 2 patients with acute lymphocytic leukemia (ALL) receiving bendamustine hydrochloride 90 mg/m2 during the phase 1 portion of the study.
Based on its mechanism of action and animal studies, bendamustine can cause fetal harm when administered to pregnant females. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
It is not known whether bendamustine is distributed into milk. Because of the potential for serious adverse reactions to bendamustine in breast-fed infants, the manufacturers do not recommend breast-feeding during bendamustine therapy and for at least 1 week after the last dose.
Pharmacokinetic and adverse effect profiles are similar to those in younger adults. In the phase 3 study in chronic lymphocytic leukemia (CLL), overall response rates for bendamustine and chlorambucil were 47 and 22%, respectively, in patients 65 years of age or older versus 70 and 30%, respectively, in those younger than 65 years of age. Median durations of progression-free survival with bendamustine and chlorambucil were 12 and 8 months, respectively, in patients 65 years of age or older versus 19 and 8 months, respectively, in those younger than 65 years of age.
Among patients with rituximab-refractory, indolent, B-cell NHL, overall response rate and duration of response in individuals 65 years of age or older were similar to results in younger adults.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.