Carmustine is available as a lyophilized product in single-dose vials containing 50 or 100 mg of drug packaged with a vial containing 3 mL of dehydrated alcohol injection, USP, for use as a diluent, or 300 mg of drug packaged with a vial containing 9 mL of dehydrated alcohol injection, USP, for use as a diluent.2079; 2229 Reconstitute by first dissolving the contents of the vial of carmustine with the appropriate amount of dehydrated alcohol injection, USP, then adding sterile water for injection to yield a concentrated solution containing 3.3 mg/mL of carmustine in 10% ethanol.2079; 2229
50-mg vial: Dissolve the contents of the 50-mg vial of carmustine with 1.5 mL of dehydrated alcohol injection, USP (from the 3-mL diluent vial) and discard the remaining volume of diluent, then add 13.5 mL of sterile water for injection.2229
100-mg vial: Dissolve the contents of the 100-mg vial of carmustine with 3 mL of dehydrated alcohol injection, USP, then add 27 mL of sterile water for injection to yield a concentrated solution containing 3.3 mg/mL of carmustine in 10% ethanol.2079
300 mg vial: Dissolve the contents of the 300-mg vial of carmustine with 9 mL of dehydrated alcohol injection, USP, then add 81 mL of sterile water for injection.2229
The reconstituted solution is a concentrate and must be further diluted for intravenous administration in sodium chloride injection or dextrose 5% in glass or polypropylene containers that are PVC- and DEHP-free.2079; 2229 Do not use PVC containers.2079; 2229
Trade Name(s)
BiCNU
Carmustine is administered by intravenous infusion over at least 2 hours, at a rate not exceeding 1.66 mg/m2/min.2079; 2229 Shorter durations may result in pain and burning at the injection site.2079; 2229
As with other cytotoxic drugs, applicable special handling and disposal procedures for carmustine should be followed.2079
Avoid accidental contact of the reconstituted solution with the skin; transient hyperpigmentation in the affected areas has occurred.2079
Intact vials of carmustine and the diluent should be stored at 2 to 8°C.2079; 2229 Intact vials are stable for 7 days at room temperatures not exceeding 25°C.1181; 1236; 1433 Room temperature storage of intact vials results in slow decomposition, with approximately 3% degradation occurring in 36 days.285 Carmustine should appear as lyophilized pale yellow flakes or a congealed mass that forms a clear, colorless to yellowish solution upon reconstitution.2079; 2229 Vials should be inspected under bright light for signs of decomposition prior to use.2079; 2229
Reconstituted solutions should be protected from light and inspected for crystal formation prior to use.2079; 2229 Crystals may be redissolved by warming the vial to room temperature with agitation.2079; 2229 Reconstituted solutions in the 100-mg vials (Avet) are stated to be stable in glass containers for 24 hours at 2 to 8°C.2079 The manufacturer of the 50- or 300-mg vials (Accord) states reconstituted solutions should be diluted immediately and not stored.2229 However, carmustine from 2 different manufacturers (Medac, Tillomed) reconstituted as recommended to a concentration of 3.3 mg/mL in the original glass vials and stored at 2 to 8°C protected from light was stable for 48 hours with drug losses of 6% (Medac) or 4.6% (Tillomed) reported.3994
Infusion solutions diluted from the 100-mg vials (Avet) to a concentration of 0.2 mg/mL should be protected from light and used within 8 hours if stored at room temperature; diluted solutions are also stated to be stable for 24 hours under refrigeration (2 to 8°C) and an additional 6 hours at room temperature protected from light.2079 Infusion solutions diluted from the 50- or 300-mg vials (Accord) to a concentration of 0.2 mg/mL should be protected from light and used within 2 hours if stored at room temperature or may be stored up to 12 hours refrigerated with an additional 2 hours at room temperature protected from light.2229
Solutions should be visually inspected for particulate matter and discoloration prior to administration.2079; 2229
Carmustine has a melting point of approximately 30.5 to 32°C.2079 At this temperature, the drug liquifies, appearing as an oily film on the vial.2079 Should this occur, the vial should be discarded, because the melting is a sign of decomposition.2079; 2229 However, one study showed that storage of the vials at 37°C for 15 minutes followed by storage at 22 to 25°C resulted in no decomposition in eight days and about an 8% loss in 37 days. Storage of the vials at 37°C for seven days resulted in about 10% decomposition.862
In 95% ethanol, carmustine 2 mg/mL is reported to be stable for at least 24 hours at 22 to 25 and 37°C.862 Under refrigeration, carmustine 0.5 to 0.6 mg/mL in 95% ethanol or absolute ethanol is stable at 0 to 5°C for up to three months.863
pH Effects
The degradation rate for carmustine in aqueous solution was reported to be at a minimum between pH 5.2 and 5.5619 and 3.3 and 4.8.1237 Above pH 6, the degradation rate increases greatly.619 Decomposition of 10% occurred in less than two hours at pH 6.5 but in 5.5 hours at optimum pH.1237
Light Effects
Solutions of carmustine should be protected from light.2079; 2229 Increased decomposition rates were reported when carmustine, in solution, was exposed to increasing intensities of light.1237 However, in another study, no clear effect on rate of carmustine loss from exposure to light was demonstrated. Some samples seemed to demonstrate increased rate of loss due to light exposure while others did not.2337
Sorption
Carmustine solution is unstable in PVC containers.2079; 2229 The manufacturer states diluted solutions should be prepared in glass or polypropylene containers only; polypropylene containers must be PVC- and DEHP-free.2079; 2229 The rate of loss of carmustine from infusion admixtures in dextrose 5% in PVC containers is substantially greater than the rate of loss in glass519; 1237; 1658; 2430 or polyolefin1237; 1658 containers.
Substantial loss to PVC, ethylene vinyl acetate, and polyurethane infusion sets was also noted. Only a set lined with polyethylene proved resistant to carmustine sorption, resulting in little loss in two hours.1237
Carmustine (Bristol-Myers Squibb) 0.2 mg/mL in dextrose 5% was evaluated for loss of drug content in glass, polyethylene, and PVC containers. At room temperature, about 40% loss of drug occurred in glass containers in 72 hours. In polyethylene containers, a slightly larger loss occurred, about 50% loss in 72 hours. The greatest loss occurred in PVC containers with about 65% loss in 72 hours. Carmustine losses of 5% occurred in 5.5 hours, 2.5 hours, and 45 minutes in glass, polyethylene, and PVC containers, respectively. The increased losses in polyethylene and PVC containers were attributed to sorption. Under refrigeration, glass and polyethylene containers were similar with less than 10% loss in 72 hours. However, in PVC containers about 20% loss due to sorption occurred in that time frame.2420; 2430
For a list of references cited in the text of this monograph, search the monograph titled References.