Cyclophosphamide is available as a dry powder in vials containing cyclophosphamide monohydrate equivalent to 500 mg, 1 g, or 2 g of cyclophosphamide.2962 Reconstitute each vial with 25, 50, or 100 mL, respectively, of sodium chloride 0.9%.2962 Sterile water for injection also may be used for reconstitution, but only if the dose is to be administered by intravenous infusion, in which case the reconstituted solution must be further diluted with a compatible intravenous infusion solution.2962 Gently swirl the vials to dissolve the powder, yielding a solution containing cyclophosphamide 20 mg/mL.2962
pH
A 22-mg/mL solution was found to have a pH of 6.87.126
Cyclophosphamide reconstituted with sodium chloride 0.9% may be administered by direct intravenous injection or by intravenous infusion.2962
Cyclophosphamide reconstituted with sterile water for injection is very hypotonic and is not suitable for direct intravenous injection.2962
For intravenous infusion, the reconstituted solution must be further diluted in a compatible intravenous infusion solution.2962
Vials containing cyclophosphamide powder should be stored at or below 25°C.2962 Vials contain no preservatives and are for single use.2962
Do not use vials that show signs of cyclophosphamide melting (e.g., clear or yellowish viscous liquid as a connected phase or in droplets).2962
Visually inspect the solution for particulate matter and discoloration prior to administration.2962 If not used immediately, solutions formed by reconstituting the dry powder with sodium chloride 0.9% may be stored for up to 24 hours at room temperature or up to 6 days under refrigeration.2962 Solutions formed by reconstituting the dry powder with sterile water for injection should be further diluted for intravenous infusion immediately; do not store.2962
Total time (from reconstitution through administration) for solutions that are further diluted with dextrose 5% or dextrose 5% in sodium chloride 0.9% should not exceed 24 hours if stored at room temperature or 36 hours if stored under refrigeration; total time for solutions further diluted with sodium chloride 0.45% should not exceed 24 hours at room temperature or 6 days under refrigeration.2962
When reconstituted with sterile water for injection or paraben-preserved bacteriostatic water for injection to a concentration of 21 mg/mL, less than 1.5% cyclophosphamide decomposition occurred within 8 hours at 24 to 27°C and within 6 days at 5°C. The rate constant for decomposition of cyclophosphamide when reconstituted with benzyl alcohol-preserved bacteriostatic water for injection was significantly higher than with sterile water for injection. It was suggested that benzyl alcohol may catalyze the decomposition of cyclophosphamide.125
The stability of cyclophosphamide 20 mg/mL, reconstituted with sterile water for injection and stored in various containers at several temperatures, was evaluated. In glass ampuls at 20 to 23°C, approximately 13 and 35% were lost in 1 and 4 weeks, respectively. Under refrigeration at 4°C or frozen at -20°C, the solution lost not more than 3% over 4 weeks.1090
Cyclophosphamide (Bristol-Myers Squibb) reconstituted with sterile water for injection to a concentration of 20 mg/mL was found to undergo about 10% degradation in 4 days at 25°C. When the solutions were stored under refrigeration at 5°C, approximately 6% loss occurred in 52 days and 10 to 12% loss occurred in 119 days.2255
Immersion of a needle with an aluminum component in cyclophosphamide (Adria) 20 mg/mL resulted in a slight darkening of the aluminum and gas production after a few days at 24°C with protection from light.988
pH Effects
Cyclophosphamide exhibits maximum solution stability over the range of 2 to 10; the rate of decomposition is essentially the same over this broad pH range.1369 At pH values less than 2 and above 11, increased rates of decomposition have been observed.1369; 2002
Syringes
In polypropylene syringes (Plastipak, Becton Dickinson) sealed with blind Luer locking hubs, the 20-mg/mL cyclophosphamide solution lost about 3% in 4 weeks at 4°C and about 10% in 11 to 14 weeks. When frozen at -20°C (with microwave thawing), the solution lost about 4% in 19 weeks. However, the syringe plungers contracted markedly during freezing, resulting in drug solution seeping past the plunger onto the inner surface of the barrel. This seeping poses the risk of bacterial contamination. Furthermore, cyclophosphamide precipitated during microwave thawing and required vigorous shaking for 5 minutes to redissolve. This precipitation during thawing appears not to occur at concentrations less than 8 mg/mL.1090
Central Venous Catheter
Cyclophosphamide (Mead Johnson) 2 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.2335
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