Source: FDA, National Drug Code (US) Revision Year: 2022
VIVIMUSTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia. Efficacy relative to first line therapies other than chlorambucil has not been established.
VIVIMUSTA is indicated for the treatment of adult 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.
The recommended dosage is 100 mg/m2 administered intravenously over 20 minutes on Days 1 and 2 of a 28-day cycle for up to 6 cycles.
Delay VIVIMUSTA for Grade 4 hematologic toxicity or clinically significant Grade 2 or greater non-hematologic toxicity.
Once non-hematologic toxicity has recovered to less than or equal to Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) greater than or equal to 1 × 109/L and platelets greater than or equal to 75 × 109/L], reinitiate VIVIMUSTA at the discretion of the healthcare provider. In addition, consider dose reduction [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.
Consider dose re-escalation in subsequent cycles at the discretion of the healthcare provider.
The recommended dosage is 120 mg/m2 administered intravenously over 20 minutes on Days 1 and 2 of a 21-day cycle for up to 8 cycles.
Delay VIVIMUSTA for Grade 4 hematologic toxicity or clinically significant Grade 2 or greater non-hematologic toxicity.
Once non-hematologic toxicity has recovered to less than or equal to Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) greater than or equal to 1 × 10 9/L and platelets greater than or equal to 75 × 10 9/L], reinitiate VIVIMUSTA at the discretion of the healthcare provider. In addition, consider dose reduction [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/m 2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m 2 on Days 1 and 2 of each cycle.
VIVIMUSTA is a hazardous drug. Follow applicable special handling and disposal procedures.1
VIVIMUSTA is a clear and colorless to yellow solution in a multiple-dose vial.
Store VIVIMUSTA refrigerated at 2°C to 8°C (36°F to 46°F). When refrigerated, the contents may partially freeze. Allow the vial to reach room temperature (15°C to 30°C or 59°F to 86°F) prior to use. Observe the contents of the vial for any visible solid or particulate matter. Do not use the product if solid or particulate matter is observed after reaching room temperature.
Aseptically withdraw the volume needed for the required dose from the 25 mg/mL solution as per Table 1 below and immediately transfer to a 250 mL infusion bag of one of the following diluents: 0.9% Sodium Chloride Injection, USP; or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP.
The resulting final concentration of bendamustine hydrochloride in the infusion bag should be within 0.1 mg/mL to 1.36 mg/mL.
After transferring, thoroughly mix the contents of the infusion bag. The admixture should be a clear and colorless to slightly yellow solution.
No other diluents have been shown to be compatible [see Dosage and Administration (2.4)].
Table 1. Volume of VIVIMUSTA required for Dilution into 250 mL of 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP for a Given Dose and Body Surface Area:
| Body Surface Area (m 2) | Volume of VIVIMUSTA to Withdraw (mL) from Vial | |||||
|---|---|---|---|---|---|---|
| 120 mg/m 2 | 100 mg/m 2 | 90 mg/m 2 | 60 mg/m 2 | 50 mg/m 2 | 25 mg/m 2 | |
| 1 | 4.8 | 4 | 3.6 | 2.4 | 2 | 1 |
| 1.1 | 5.3 | 4.4 | 4 | 2.6 | 2.2 | 1.1 |
| 1.2 | 5.8 | 4.8 | 4.3 | 2.9 | 2.4 | 1.2 |
| 1.3 | 6.2 | 5.2 | 4.7 | 3.1 | 2.6 | 1.3 |
| 1.4 | 6.7 | 5.6 | 5 | 3.4 | 2.8 | 1.4 |
| 1.5 | 7.2 | 6 | 5.4 | 3.6 | 3 | 1.5 |
| 1.6 | 7.7 | 6.4 | 5.8 | 3.8 | 3.2 | 1.6 |
| 1.7 | 8.2 | 6.8 | 6.1 | 4.1 | 3.4 | 1.7 |
| 1.8 | 8.6 | 7.2 | 6.5 | 4.3 | 3.6 | 1.8 |
| 1.9 | 9.1 | 7.6 | 6.8 | 4.6 | 3.8 | 1.9 |
| 2 | 9.6 | 8 | 7.2 | 4.8 | 4 | 2 |
| 2.1 | 10.1 | 8.4 | 7.6 | 5 | 4.2 | 2.1 |
| 2.2 | 10.6 | 8.8 | 7.9 | 5.3 | 4.4 | 2.2 |
| 2.3 | 11 | 9.2 | 8.3 | 5.5 | 4.6 | 2.3 |
| 2.4 | 11.5 | 9.6 | 8.6 | 5.8 | 4.8 | 2.4 |
| 2.5 | 12 | 10 | 9 | 6 | 5 | 2.5 |
| 2.6 | 12.5 | 10.4 | 9.4 | 6.2 | 5.2 | 2.6 |
| 2.7 | 13 | 10.8 | 9.7 | 6.5 | 5.4 | 2.7 |
| 2.8 | 13.4 | 11.2 | 10.1 | 6.7 | 5.6 | 2.8 |
| 2.9 | 13.9 | 11.6 | 10.4 | 7 | 5.8 | 2.9 |
| 3 | 14.4 | 12 | 10.8 | 7.2 | 6 | 3 |
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Discard any unused solution according to institutional procedures for hazardous drugs.
VIVIMUSTA contains no antimicrobial preservative. Prepare the admixture as close as possible to the time of patient administration.
Once diluted with 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 refrigerated conditions (2°C to 8°C or 36°F to 46°F) or for 3 hours when stored at room temperature (15°C to 30°C or 59°F to 86°F) and room light. Complete administration of diluted VIVIMUSTA within this period of time.
VIVIMUSTA (bendamustine hydrochloride injection) is supplied in a multiple-dose vial. Retain the partially used vial in original package to protect from light and store refrigerated (2°C to 8°C or 36°F to 46°F) if additional dose withdrawal from the same vial is intended.
VIVIMUSTA is supplied as a multiple-dose vial. Although it does not contain any antimicrobial preservative, VIVIMUSTA is bacteriostatic. The partially used vials are stable for up to 28 days when stored in its original carton under refrigeration (2°C to 8°C or 36°F to 46°F). Each vial is not recommended for more than a total of six (6) dose withdrawals.
After first use, store the partially used vial in the original carton at 2°C to 8°C (36°F to 46°F) and then discard after 28 days.
The intravenous lethal dose 50 (LD50) of bendamustine hydrochloride is 240 mg/m2 in the mouse and rat. Toxicities included sedation, tremor, ataxia, convulsions and respiratory distress.
Across all clinical experience, the reported maximum single dose received was 280 mg/m2. Three of four patients who received this dose showed ECG changes considered dose-limiting at 7 and 21 days post-dosing. These changes included QT prolongation (one patient), sinus tachycardia (one patient), ST and T wave deviations (two patients) and left anterior fascicular block (one patient). Cardiac enzymes and ejection fractions remained normal in all patients.
No specific antidote for bendamustine hydrochloride overdose is known. Management of overdosage should include general supportive measures, including monitoring of hematologic parameters and ECGs.
VIVIMUSTA (bendamustine hydrochloride injection) is a hazardous drug. Follow applicable special handling and disposal procedures1. Care should be exercised in the handling and preparation of solutions prepared from VIVIMUSTA. The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If gloves come in contact with VIVIMUSTA prior to dilution, remove gloves and follow disposal procedures. If a solution of VIVIMUSTA (bendamustine hydrochloride injection) contacts the skin, wash the skin immediately and thoroughly with soap and water. If VIVIMUSTA (bendamustine hydrochloride injection) contacts the mucous membranes, flush thoroughly with water.
Store VIVIMUSTA (bendamustine hydrochloride injection) refrigerated at 2°C to 8°C (36°F to 46°F). Retain in original carton until time of use to protect from light.
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