AHFS Class:

10:00 Antineoplastic Agents

Generic Name

• CycloPHOSphamide (CAS Registry Number: 6055-19-2)

Cyclophosphamide is available as a powder in single-dose 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 Shake the vial vigorously 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 is administered by direct intravenous injection following reconstitution with sodium chloride 0.9% or by intravenous infusion following reconstitution and dilution.²⁹⁶² Cyclophosphamide reconstituted with sterile water for injection is hypotonic and is not suitable for direct intravenous injection.²⁹⁶² For intravenous infusion, the reconstituted solution must be further diluted to a minimum concentration of 2 mg/mL in a compatible intravenous infusion solution.²⁹⁶² The manufacturer recommends dilution in dextrose 5%, dextrose 5% in sodium chloride 0.9%, or sodium chloride 0.45%.²⁹⁶²

The drug should be injected or infused very slowly to reduce the risk of rate-dependent adverse reactions.²⁹⁶²

Intact vials should be stored at or below 25°C.²⁹⁶²

Cyclophosphamide is a white powder.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 reconstituted 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 reconstituted with sterile water for injection should be further diluted for intravenous infusion immediately; do not store.²⁹⁶²

If further diluted in dextrose 5% or dextrose 5% in sodium chloride 0.9%, the storage time (i.e., the total time cyclophosphamide is in solution from time of reconstitution) should not exceed 36 hours under refrigeration or 24 hours at room temperature.²⁹⁶² If further diluted in sodium chloride 0.45%, total storage time should not exceed 6 days under refrigeration or 24 hours at room temperature.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

Solution Compatibility

Additive Compatibility

Drugs in Syringe Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

For a list of references cited in the text of this monograph, search the monograph titled References.

ASHP^® Injectable Drug Information^TM. Selected Revisions September 30, 2026. © Copyright, 2026. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.