Thursday, April 8, 2021

Bendit, Bendamustine Hydrochloride for Injection (Generic version of Treanda)

 What is Treanda? how to use?

Treanda (bendamustine hydrochloride injection) is an antitumor drug (anticancer drug) used to treat chronic lymphocytic leukemia. After unsuccessful treatment of other drugs, Treanda was used to treat indolent B-cell non-Hodgkin's lymphoma.

What are side effects of Treanda?

Common side effects of Treanda include:

  • nausea
  • vomiting
  • diarrhea
  • tiredness
  • weakness
  • mouth sores
  • constipation
  • upset stomach
  • swelling in your hands or feet
  • headache
  • dizziness
  • drowsiness
  • loss of appetite
  • weight loss
  • mild skin rash
Description
Bendamustine hydrochloride is an alkylating agent. The chemical name of bendamustine hydrochloride is 1H-benzimidazole-2-butyric acid, 5-[bis(2-chloroethyl)amino] -1 methyl monohydrochloride. Its empirical formula is C16H21Cl2N3O2·HCl, and its molecular weight is 394.7. Bendamustine hydrochloride contains a methylethylamino group and a benzimidazole heterocyclic ring with a butyric acid substituent, and has the following structural formula:

TREANDA injection (45 mg / 0.5 mL or 180 mg / 2 mL solution)
TREANDA (bendamustine hydrochloride) injection can only be administered intravenously after being diluted with 0.9% sodium chloride injection (USP) or 2.5% glucose/0.45% sodium chloride injection (USP). It is provided in a single-dose vial as a sterile clear, colorless to yellow solution at a concentration of 90 mg/mL bendamustine hydrochloride. Each 0.5 ml vial contains 45 mg of bendamustine hydrochloride, 162 mg of USP propylene glycol and 293 mg of N,N-dimethylacetamide, EP. Each 2 ml vial contains 180 mg of bendamustine hydrochloride, 648 mg of USP propylene glycol and 1172 mg of N,N-dimethylacetamide (EP). Each vial contains 0.2 ml of overfill.

TREANDA for injection (25 mg/vial or 100 mg/vial lyophilized powder)
TREANDA for injection (bendamustine hydrochloride hydrochloride) is only formulated with sterile water for injection (USP), and after injection with 0.9% sodium chloride injection (USP) or 2.5% dextrose/0.45% sodium chloride Intravenous infusion can only be carried out after further dilution of USP. It is provided in a single-dose vial as a sterile, non-pyrogenic white to off-white lyophilized powder. 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.

Indications
Chronic Lymphocytic Leukemia (CLL)
TREANDA® is suitable for the treatment of patients with chronic lymphocytic leukemia. The efficacy of first-line therapies other than chlorambucil has not been determined.

Non-Hodgkin's Lymphoma (NHL)
TREANDA is designated for the treatment of patients with indolent B-cell non-Hodgkin lymphoma who have progressed during or within six months of rituximab or rituximab-containing treatment regimens.

Dosage and administration
Select the TREANDA recipe to be managed
There are two formulations of TREANDA, namely solution (TREANDA injection) and lyophilized powder (TREANDA for injection).

If you want to use a closed system transmission device (CSTD), adapter, and syringe containing polycarbonate or acrylonitrile-butadiene-styrene (ABS) before being diluted in an infusion bag, please do not use TREANDA injection [see Preparation for intravenous administration].

If you use a syringe to take out TREANDA injection from the vial and transfer it to an infusion bag, you can only use a polypropylene syringe with a metal needle and polypropylene connector to take out TREANDA injection and transfer it to the infusion bag. The appearance of the polypropylene syringe is translucent.
TREANDA injection and recombinant TREANDA injection have different concentrations of bendamustine hydrochloride. The concentration of bendamustine hydrochloride in the solution was 90 mg/mL, and the concentration of bendamustine hydrochloride in the lyophilized powder reconstituted solution was 5 mg/mL. Do not mix or combine the two formulas.

The TREANDA injection must be withdrawn and transferred to a biological safety cabinet (BSC) or safety isolator for dilution using a polypropylene syringe with a metal needle and a polypropylene needle seat.

If CSTD or adaptor containing polycarbonate or ABS is used as a supplementary protective agent1 before dilution, only TREANDA injection (lyophilized powder formulation) can be used [please refer to the method provided]
Dosage instructions for CLL
Recommended dosage
The recommended dose is 100 mg/m2 administered intravenously within 30 minutes on Day 1 and Day 2 of a 28-day cycle for a maximum of 6 cycles.

Delay in dose of CLL, dose modification and treatment restart
If Grade 4 hematological toxicity or clinically ≥ Grade 2 non-hematological toxicity occurs, the administration of TREANDA should be delayed. Once the non-hematological toxicity returns to ≤1 grade and/or the blood count is improved [absolute neutrophil count (ANC) ≥1 x 109/L, platelet ≥75 x 109/L], TREANDA can be restarted according to the following conditions Attending physician. In addition, the dose may need to be reduced. [See warnings and cautions]
Change the dose of blood toxicity: For toxicity of grade 3 or higher, reduce the dose to 50 mg/m2 on the 1st and 2nd day of each cycle; if toxicity of grade 3 or higher occurs again, in each Decrease the dose to 25 mg/m2 on Day 1 and Day 2 of the cycle.

Dose modification for non-hematological toxicity: For clinically significant grade 3 or higher toxicity, reduce the dose to 50 mg/m2 on the 1st and 2nd day of each cycle.

The attending physician may consider increasing the dose in subsequent cycles as appropriate.
NHL dosage instructions
Recommended dosage
On Days 1 and 2 of the 21-day cycle, the recommended intravenous dose is 120 mg/m2 within 60 minutes for a maximum of 8 cycles.

NHL dose delay, dose modification and treatment restart
If Grade 4 hematological toxicity or clinically ≥ Grade 2 non-hematological toxicity occurs, the administration of TREANDA should be delayed. Once the non-hematological toxicity returns to ≤1 grade and/or the blood count is improved [absolute neutrophil count (ANC) ≥1 x 109/L, platelet ≥75 x 109/L], TREANDA can be restarted according to the following conditions Attending physician. In addition, the dose may need to be reduced. [See warnings and cautions]
Change the dose of hematological toxicity: For grade 4 toxicity, reduce the dose to 90 mg/m2 on the 1st and 2nd day of each cycle; if grade 4 toxicity occurs again, on the 1st and the first day of each cycle Reduce the dose to 60 mg/m2 in 2 days.

Dose adjustment for non-hematological toxicity: For toxicity of grade 3 or higher, reduce the dose to 90 mg/m2 on the 1st and 2nd day of each cycle; if toxicity of grade 3 or higher recurs, then Reduce the dose to 60 mg/m2 on Day 1 and Day 2 of each cycle.
Preparation for intravenous administration
TREANDA is a cytotoxic drug. Please follow applicable special handling and disposal procedures.

TREANDA injection (45 mg / 0.5 mL or 180 mg / 2 mL solution)
TREANDA Injection must be diluted in a biological safety cabinet (BSC) or isolator.
When preparing the concentrated TREANDA injection and transferring it to the infusion bag, do not use equipment containing polycarbonate or ABS. However, after diluting TREANDA Injection into an infusion bag, devices containing polycarbonate or ABS can be used, including infusion sets.
TREANDA injection contains N,N-dimethylacetamide (DMA) and is not compatible with devices containing polycarbonate or ABS. It has been shown that devices containing polycarbonate or ABS (including CSTD, adapters and syringes) will dissolve when in contact with DMA present in the product. This incompatibility can lead to equipment failure (such as CSTD component leakage, damage or operational failure), possible product contamination, and potentially serious adverse health consequences for practitioners, including skin reactions; or for patients, including but not limited to if Small blood vessels receiving products contaminated with dissolved ABS or polycarbonate may cause blockage of small blood vessels. Equipment compatible with diluted TREANDA injection can be provided.
If you use a syringe to take out TREANDA injection from the vial and transfer it to an infusion bag, you can only use a polypropylene syringe with a metal needle and polypropylene connector to take out TREANDA injection and transfer it to the infusion bag.
Each bottle of TREANDA injection can only be used in a single dose.
Using a polypropylene syringe with a metal needle and a polypropylene sleeve, aseptically extract the volume required for the required dose from the 90 mg/mL solution.
Immediately transfer the solution to a 500 mL 0.9% sodium chloride injection USP (normal saline) infusion bag. As an alternative to 0.9% sodium chloride injection USP (normal saline), 500 mL 2.5% glucose/0.45% sodium chloride injection USP infusion bag can be considered. The final final concentration of bendamustine hydrochloride in the infusion bag should be within 0.2 – 0.7 mg/mL.
After diluting TREANDA Injection into an infusion bag, you can use equipment containing polycarbonate or ABS, including an infusion set.
Before administration, visually inspect the filled syringe and the prepared infusion bag to ensure that there are no visible particles. The admixture should be a colorless to yellow transparent solution
As mentioned above, use 0.9% sodium chloride injection (USP) or 2.5% glucose/0.45% sodium chloride injection (USP) for dilution. No other thinners have proven to be compatible.
If you want to use a closed system transmission device or an adapter containing polycarbonate or ABS as supplementary protection during the preparation process, please use only TREANDA injections (lyophilized formulations).
Each vial of TREANDA injection can only be used in a single dose.
Reconstitute each TREANDA injection vial aseptically as follows:
25 mg TREANDA vial for injection: add only 5 mL sterile water for injection, USP.
TREANDA 100 mg vial for injection: add only 20 mL of sterile water for injection, USP.
Shake thoroughly to obtain a transparent, colorless to light yellow solution with a concentration of 5 mg/mL bendamustine hydrochloride. The lyophilized powder should be completely dissolved within 5 minutes. The reconstituted solution must be transferred to the infusion bag within 30 minutes after reconstitution. If particulate matter is observed, recycled products must not be used.
Aseptically draw the required volume of the required dose (based on a concentration of 5 mg/mL), and then immediately transfer it to a 500 mL 0.9% sodium chloride injection USP (normal saline) infusion bag. As an alternative to 0.9% sodium chloride injection USP (normal saline), 500 mL 2.5% glucose/0.45% sodium chloride injection USP infusion bag can be considered. The final final concentration of bendamustine hydrochloride in the infusion bag should be within 0.2 – 0.6 mg/mL. After transferring, mix the contents of the infusion bag thoroughly.
Before administration, visually inspect the filled syringe and the prepared infusion bag to ensure that there are no visible particles. The mixture should be a transparent colorless to light yellow solution.
As mentioned above, use sterile water for injection (USP) for preparation, and then use 0.9% sodium chloride injection (USP) or 2.5% glucose/0.45% sodium chloride injection (USP) for dilution, as described above. No other thinners have proven to be compatible.

General information
When the solution and container permit, the parenteral drug should be visually inspected for particulate matter and discoloration before administration. Any unused solution should be discarded in accordance with the institutional procedures for anti-tumor drugs.

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