Bendamustine hydrochloride is available in several formulations that may differ in stability, incompatibilities, and directions for dilution and administration.2994; 3098; 3456
Bendamustine hydrochloride (Treanda) is available as a lyophilized powder in single-dose vials containing 25 or 100 mg of bendamustine hydrochloride and 42.5 or 170 mg of mannitol, respectively.2994 The vials should be reconstituted only with sterile water for injection (5 or 20 mL, respectively) and shaken well to dissolve.2994 The powder should completely dissolve within 5 minutes to yield a reconstituted solution with a bendamustine hydrochloride concentration of 5 mg/mL.2994 If particulate matter is present, the reconstituted solution should be discarded.2994 The reconstituted solution must be further diluted prior to administration.2994 Within 30 minutes of reconstitution, the appropriate volume of the reconstituted solution should be withdrawn from the vial and immediately diluted in an infusion bag containing 500 mL of sodium chloride 0.9% or dextrose 2.5% in sodium chloride 0.45% prior to administration.2994 The contents of the infusion bag should be thoroughly mixed following transfer of the reconstituted solution.2994 The resulting concentration of bendamustine hydrochloride diluted in the infusion bag should be within the range of 0.2 to 0.6 mg/mL.2994
Bendamustine hydrochloride (Bendeka) is available as a 25 mg/mL ready-to-dilute concentrate for injection in 4-mL multidose vials containing 100 mg of bendamustine hydrochloride.3098 Each mL of solution also contains propylene glycol 0.1 mL and monothioglycerol 5 mg in polyethylene glycol 400.3098 Sodium hydroxide also may have been added to adjust the pH.3098 Although the multidose vials do not contain any antimicrobial preservative, the drug is bacteriostatic.3098 Bendamustine hydrochloride concentrate for injection must be diluted prior to infusion.3098 Vials should be stored under refrigeration at 2 to 8°C; however, under such storage conditions, the contents of the vials may partially freeze.3098 Vials should be allowed to reach room temperature prior to preparation of the infusion.3098 If particulate matter is observed once the vial has warmed to room temperature, the vial should not be used.3098 The appropriate volume of the solution should be withdrawn from the vial and immediately diluted in an infusion bag containing 50 mL of sodium chloride 0.9%, dextrose 2.5% in sodium chloride 0.45%, or dextrose 5%, and the contents of the infusion bag should be thoroughly mixed.3098 The resulting concentration of bendamustine hydrochloride in the infusion bag should be within the range of 1.85 to 5.6 mg/mL.3098
Bendamustine hydrochloride (Eagle) is available as a 25-mg/mL ready-to-dilute concentrate for injection in 4-mL multidose vials containing 100 mg of bendamustine hydrochloride.3456 Each mL of solution also contains propylene glycol 0.1 mL and monothioglycerol 5 mg in polyethylene glycol 400.3456 Although the multidose vials do not contain any antimicrobial preservative, the drug is bacteriostatic.3456 Bendamustine hydrochloride concentrate for injection must be diluted prior to infusion.3456 Vials should be stored under refrigeration at 2 to 8°C; however, under such storage conditions, the contents of the vials may partially freeze.3456 Vials should be allowed to reach room temperature prior to preparation of the infusion.3456 If particulate matter is observed once the vial has warmed to room temperature, the vial should not be used.3456 The appropriate volume of the solution should be withdrawn from the vial and immediately diluted in an infusion bag containing 500 mL of sodium chloride 0.9% or dextrose 2.5% in sodium chloride 0.45%, and the contents of the infusion bag should be thoroughly mixed.3456 The resulting concentration of bendamustine hydrochloride in the infusion bag should be within the range of 0.2 to 0.7 mg/mL.3456
pH
The solution reconstituted from the lyophilized powder has a pH of 2.5 to 3.5.2994
Trade Name(s)
Bendeka, Treanda
Bendamustine hydrochloride is administered by intravenous infusion after dilution of the appropriate volume of the reconstituted solution or concentrate for injection in a compatible diluent;2994; 3098; 3456 specific product labeling should be consulted for additional administration details.
Care should be taken to ensure good venous access prior to starting the infusion, and the infusion site should be monitored during and after the infusion;2994; 3098; 3456 extravasation should be avoided.2994; 3098; 3456
As with other cytotoxic drugs, bendamustine hydrochloride should be prepared and administered using protective measures to avoid inadvertent contact with the drug in the case of breakage of the vial or other accidental spillage.2994; 2996; 3098; 3456 Hands should be washed both before and after handling the drug.2996 Gloves and protective clothing (e.g., laboratory coat, eye protection) are recommended in the preparation of the drug.2994; 2996; 3456 Gloves that come in contact with bendamustine hydrochloride concentrate prior to dilution should be removed and properly disposed of.2994; 3456 If skin contact with the drug occurs, the exposed area should be washed thoroughly with soap and water.2994; 3098; 3456 For mucous membrane contact, the exposed area should be flushed thoroughly with water.2994; 3098; 3456 Applicable disposal procedures for the drug should be followed.2994; 3098; 3456
Bendamustine hydrochloride lyophilized powder for injection (Treanda) is a white to off-white powder that forms a clear, colorless to pale yellow solution when reconstituted as directed with sterile water for injection.2994 Intact vials of the lyophilized powder should be stored at controlled room temperature in the original package to protect from light.2994 Short excursions not exceeding 2 days at -20 to 40°C are permitted for the intact 100-mg vials of lyophilized powder when stored in the original unopened carton.2996 The reconstituted solution must be diluted within 30 minutes of reconstitution.2994 Syringes containing the reconstituted solution and subsequently prepared infusions bags should be visually inspected to ensure the absence of particulate matter prior to administration.2994 After dilution in sodium chloride 0.9% or dextrose 2.5% in sodium chloride 0.45%, the solution should be clear and colorless to slightly yellow in color.2994
Bendamustine hydrochloride concentrates for injection are clear, colorless to yellow solutions.3098; 3456 Intact vials of the concentrates for injection should be stored at 2 to 8°C in the original carton to protect from light.3098; 3456 When refrigerated, the contents of the vials may partially freeze.3098; 3456 Vials should be allowed to come to room temperature (15 to 30°C) prior to use.3098; 3456 Multidose vials do not contain any antimicrobial preservative, but the drug is bacteriostatic.3098; 3456 Partially used multidose vials may be stored for up to 28 days at 2 to 8°C in their original carton following initial puncture.3098; 3456 Vials should be discarded 28 days after initial entry and should not be used for more than a total of 6 withdrawals.3098; 3456 Vials and subsequently prepared infusion bags should be visually inspected to ensure the absence of particulate matter prior to administration.3098; 3456 After dilution in a compatible diluent, the solution should remain clear and colorless to yellow or slightly yellow.3098; 3456
The manufacturers state that admixtures of bendamustine hydrochloride should be prepared (from any of the formulations) as close to the time of administration as possible.2994; 3098; 3456
Incompatibilities with Devices Containing Polycarbonate or Acrylonitrile-butadiene-styrene
Some previous formulations of bendamustine hydrochloride contained N,N-dimethylacetamide (DMA), which is incompatible with polycarbonate or acrylonitrile-butadiene-styrene (ABS) and devices containing these compounds (e.g., many closed-system transfer devices [CSTDs], adapters, syringes).2994; 2995; 2997; 3044; 3045 Such devices had been shown to dissolve upon contact with DMA, leading to device failure (e.g., leaking, breaking or operational failure of CSTD components), potential contamination of the drug, and potential serious adverse effects in the patient (e.g., risk of small vessel blockage) or for the practitioner who prepared and/or administered the drug (e.g., skin reactions).2994; 2995; 2997; 3044; 3045 Current commercially available formulations of bendamustine hydrochloride no longer contain DMA.2994; 3098; 3456
For a list of references cited in the text of this monograph, search the monograph titled References.