Etoposide phosphate is available as a lyophilized powder in single-dose vials containing the equivalent of 100 mg of etoposide as the phosphate along with sodium citrate 32.7 mg and 300 mg of dextran 40.3721 Reconstitute with 5 or 10 mL of compatible diluent to yield solutions of 20 or 10 mg/mL, respectively.3721 Sterile water for injection, dextrose 5%, sodium chloride 0.9%, bacteriostatic water for injection preserved with benzyl alcohol, or bacteriostatic sodium chloride 0.9% preserved with benzyl alcohol may be used for reconstitution.3721
pH
Reconstitution with sterile water for injection to a concentration of 1 mg/mL results in a pH of approximately 2.9.4
Trade Name(s)
Etopophos
Etoposide phosphate is administered by intravenous infusion over 5 minutes to 3.5 hours.3721 It should not be given by bolus intravenous injection.3721 The reconstituted drug may be given without further dilution or may be diluted to a concentration as low as 0.1 mg/mL with dextrose 5% or sodium chloride 0.9%.3721
Extravasation may result in swelling, pain, cellulitis, and skin necrosis.3721
Etoposide phosphate is a white to off-white lyophilized powder.3721 Intact vials should be stored under refrigeration at 2 to 8°C and protected from light.3721
The manufacturer states that etoposide phosphate reconstituted with an unpreserved diluent (such as sterile water for injection, dextrose 5%, or sodium chloride 0.9%) may be stored for 24 hours at controlled room temperature or 7 days under refrigeration at 2 to 8°C.3721 If a diluent containing benzyl alcohol as a preservative (such as bacteriostatic water for injection or bacteriostatic sodium chloride 0.9%) is used to reconstitute etoposide phosphate, the solution may be stored for 48 hours at room temperature or 7 days under refrigeration at 2 to 8°C.3721
Unlike etoposide, the phosphate ester is highly water soluble, having a solubility over 100 mg/mL.4 Consequently, the potential for precipitation in aqueous media is reduced greatly compared with the older surfactant- and organic solvent-based formulation.2219
Etoposide production by hydrolysis from infusion admixtures of etoposide phosphate (Bristol-Myers Squibb) was measured. The admixtures, equivalent to etoposide 1.5 mg/mL in 66.7 mL and 15 mg/mL in 20 mL of sodium chloride 0.9%, were filled into polyvinyl chloride (PVC) ambulatory infusion pump reservoirs (Pharmacia Deltec) and stored at 20 and 37°C protected from light. Etoposide levels in the etoposide phosphate admixtures increased at both temperatures; in 7 days the increase in concentration was about 2% at 20°C and about 7% at 37°C. The authors concluded that etoposide phosphate is suitable for multiple-day ambulatory infusion.2024
Doxorubicin hydrochloride, etoposide phosphate, and vincristine sulfate admixtures at a variety of concentrations were unable to pass the USP test for antimicrobial effectiveness. Mixtures of these drugs are not “self-preserving” and permit microbial growth.2343
Etoposide phosphate (Bristol Myers Squibb) 0.09 mg/mL in sodium chloride 0.9% did not result in the loss of viability of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Candida albicans within 120 hours at 22°C. Diluted solutions should be stored under refrigeration whenever possible, and the potential for microbiological growth should be considered when assigning expiration periods.2740
Light Effects
An evaluation of etoposide phosphate (Bristol-Myers Squibb) 2 mg/mL, doxorubicin hydrochloride 0.4 mg/mL, and vincristine sulfate 0.016 mg/mL (16 mcg/mL) in sodium chloride 0.9% in polyolefin plastic bags (McGaw) found little or no effect of constant exposure to normal fluorescent room light for 124 hours. The admixtures were physically compatible, and all 3 drugs in the admixture remained stable throughout the time stored at an elevated temperature of 35 to 40°C.2343
Syringes
Etoposide phosphate (Bristol Laboratories Oncology Products) 10 and 20 mg/mL was prepared with bacteriostatic water for injection preserved with benzyl alcohol 0.9% (Abbott). The solutions were packaged as 4 mL of solution in 5-mL polypropylene syringes (Becton Dickinson) and sealed with tip caps (Red Cap, Burron Medical). The syringes were stored at 32°C for 7 days, 23°C for 31 days, and 4°C for 31 days. All samples were physically stable, with no visual change and no increase in measured haze or particle content, and little drug loss occurred. At 32°C, 2 to 4% loss occurred in 7 days. At 23°C, about 6 to 7% loss occurred in 31 days. Losses under refrigeration were 4% or less in 31 days.2219
For a list of references cited in the text of this monograph, search the monograph titled References.