Busulfan is available as a 6-mg/mL concentrate for injection; busulfan is dissolved in a vehicle composed of 33% (v/v) N,N-dimethylacetamide (DMA) (approximately 309 mg DMA per mL of busulfan solution) and 67% (v/v) polyethylene glycol 400.2982; 3047 The concentrate for injection is packaged in 10-mL single-dose vials and must be diluted for administration.2982
pH
Busulfan diluted for infusion to a concentration of approximately 0.5 mg/mL with sodium chloride 0.9% or dextrose 5% has a pH of 3.4 to 3.9, depending on which solution is used.2982
Trade Name(s)
Busulfex
Busulfan concentrate for injection must be diluted prior to administration.2982 Sodium chloride 0.9% and dextrose 5% are both recommended diluents for dilution of busulfan concentrate for injection.2982 The volume of infusion solution used for dilution should be 10 times the volume of the busulfan concentrate for injection dose to ensure that the final concentration is approximately 0.5 mg/mL.2982
Busulfan admixtures should be administered intravenously through a central venous catheter as a 2-hour infusion.2982 More rapid infusion has not been tested and is not recommended.2982 An infusion pump should be used to control the flow rate.2982 The central venous catheter should be flushed before and after busulfan administration with approximately 5 mL of sodium chloride 0.9% or dextrose 5%.2982 The manufacturer states that an administration set with a minimal residual volume (2 to 5 mL) should be used for busulfan administration.2982
As with other toxic drugs, caution should be exercised in the handling and preparation of busulfan, and applicable special handling and disposal procedures should be followed.2982 Appropriate gloves should be worn during preparation; accidental skin exposure may result in skin reactions.2982 The busulfan is added into an intravenous solution bag that already contains the appropriate amount of sodium chloride 0.9% or dextrose 5%.2982 The drug should always be added to the diluent, not the diluent to the drug.2982 The solution should be mixed thoroughly by inverting the bag several times.2982 Other diluents should not be used.2982
Busulfan (Pierre Fabre) 6 mg/mL was found to be incompatible with the silicone SmartSite needle-free valve of the MFX 2301E tubing set (CareFusion).2983 Slight turbidity was noted immediately on injection of the busulfan into the valve and persisted throughout the 5-hour study period.2983
Polycarbonate syringes and filter needles should not be used with busulfan;2982 the manufacturer notes that a precipitate has been known to form when syringes composed of or containing polycarbonate are used to withdraw busulfan from the vial.3046
Busulfan concentrate for injection is a clear, colorless solution.2982 Intact vials must be stored under refrigeration at 2 to 8°C.2982 Solutions should be visually inspected for particulate matter and discoloration prior to administration; if particulate matter is observed in the vial, the concentrate for injection should not be used.2982
Administration of busulfan diluted for infusion in sodium chloride 0.9% or dextrose 5% should be completed within 8 hours when stored at 25°C.2982 Administration of busulfan diluted for infusion in sodium chloride 0.9% should be completed within 12 hours when stored under refrigeration at 2 to 8°C.2982
Busulfan (Pierre Fabre) 6 mg/mL did not support the growth of Staphylococcus aureus and Candida albicans within 2 hours at room temperature.2740 Busulfan 0.5 mg/mL in sodium chloride 0.9% did not support the growth of Staphylococcus aureus, Enterococcus faecium, or Pseudomonas aeruginosa with loss of viability over 24 to 48 hours at room temperature but had no effect on the growth of Candida albicans.2740 Diluted solutions should be stored under refrigeration whenever possible, and the potential for microbiological growth should be considered when assigning expiration periods.2740
Syringes
Busulfan (Pierre Fabre) 0.54 mg/mL in 0.9% sodium chloride stored in 50-mL polypropylene syringes (Becton Dickinson) fitted with tip caps (Braun) and protected from light at 2 to 8°C or 23 to 27°C was visually compatible and demonstrated less than 10% loss in 30 or 12 hours, respectively.3399 White crystals were detected on the surface of the syringes after 33 hours at 2 to 8°C.3399
For a list of references cited in the text of this monograph, search the monograph titled References.