Cytarabine injection is available as a 20-mg/mL solution in 5-mL single-use vials,2942 25-mL multidose vials,2944 and 50-mL pharmacy bulk vials.2943 Preservative-free 5-mL vials and 50-mL pharmacy bulk vials contain sodium chloride 6.8 mg/mL in water for injection.2942; 2943 The 25-mL multidose vial contains benzyl alcohol 0.9% in water for injection.2944 Hydrochloric acid and/or sodium hydroxide may have been added to any of these vials during manufacturing to adjust pH.2942; 2943; 2944
Cytarabine injection also is available as a 100-mg/mL solution in preservative-free, single-use 20-mL vials in water for injection.2941; 2942 Hydrochloric acid and/or sodium hydroxide may have been added during manufacturing to adjust pH.2941; 2942
CAUTION: Care should be taken to ensure that the correct drug product, dose, and administration procedures are used and that no confusion with other products occurs.
pH
Preservative-free cytarabine 20-mg/mL injection solution has a pH of 7.4.2942; 2943 Cytarabine 20-mg/mL injection solution in multidose vials containing benzyl alcohol has a pH of 7.6.2944 Preservative-free cytarabine 100-mg/mL injection solution has a pH of 7.7.2941; 2942
Sodium Content
Preservative-free cytarabine 20-mg/mL injection contains 0.12 mEq of sodium per mL.2942; 2943
Cytarabine may be administered by subcutaneous or intrathecal (preservative-free preparations only) routes, or intravenously by direct injection or continuous or intermittent infusion.2941; 2942; 2943; 2944 Some preparations contain preservatives and should not be used for intrathecal administration.2944 Preservative-free pharmacy bulk vials are intended only for the preparation of solutions for intravenous infusion.2943
CAUTION: Care should be taken to ensure that the correct drug product, dose, and administration procedures are used and that no confusion with other products occurs.
Intact vials of cytarabine injection should be stored at controlled room temperature and protected from light.2941; 2942; 2943; 2944 Cytarabine 100-mg/mL solutions should not be refrigerated.2941 If a precipitate has formed as a result of exposure of the 100-mg/mL solution to low temperatures, the drug may be redissolved by warming the vial up to 55°C for no longer than 30 minutes, under dry heat conditions, and shaking until the precipitate has dissolved.2941
A stability study of cytarabine in aqueous solution showed maximum stability in the neutral pH range. It was calculated to retain 90% for 6.5 months at pH 6.9 at 25°C. The rate of decomposition of cytarabine in alkaline solutions is about 10 times as great as in acid solutions.82
One manufacturer indicated that for concentrations of 20 and 250 mg/mL in bacteriostatic water for injection, greater than 99% was retained after 5 days of storage at room temperature.174 However, cytarabine has an aqueous solubility of 100 mg/mL,4; 1369 and precipitation from more highly concentrated solutions has been observed in varying time frames. In another test, concentrations of 40 and 80 mg/mL in bacteriostatic water for injection were stored in plastic syringes (Becton Dickinson) at 37, 25, 4, and -20°C. Cytarabine remained stable for at least 15 days at 25 and 4°C and for 7 days at 37°C. However, storage at -20°C resulted in a precipitate.174
Immersion of a needle with an aluminum component in cytarabine (Upjohn) 20 mg/mL resulted in no visually apparent reaction after 7 days at 24°C.988
Cytarabine 12.5 mg/mL in sodium chloride 0.9% did not inhibit the growth of inoculated Staphylococcus epidermidis during 21 days at 35°C. At a concentration of 50 mg/mL in sodium chloride, the viability was reduced but not eliminated.1659 The potential for microbiological growth should be considered when assigning expiration periods.
Syringes
Cytarabine (Upjohn) 50 mg/mL in polypropylene syringes containing 5, 10, and 20 mL was stable for 29 days at 8 and 21°C in the dark, exhibiting losses of 8.5% or less.1566
Cytarabine (Upjohn) 50 mg/2.5 mL was stored at 5 and 25°C in 5-mL plastic syringes (Becton Dickinson) with rubber tip caps and in glass flasks covered with parafilm. After 7 days, samples in the plastic syringes showed a 2 to 3% loss of cytarabine at both temperatures. The 25°C sample in glass also showed a 2% loss, but the 5°C sample in glass showed no loss after 7 days.759
Intrathecal Injections
Bacterially contaminated intrathecal solutions could pose very grave risks; consequently, solutions for intrathecal use should be administered as soon as possible after preparation.328
The stability and compatibility of cytarabine (Upjohn), methotrexate (NCI), and hydrocortisone (Upjohn), mixed together in intrathecal injections, were evaluated. Two combinations were tested: (1) cytarabine 50 mg, methotrexate 12 mg (as the sodium salt), and hydrocortisone 25 mg (as the sodium succinate salt); and (2) cytarabine 30 mg, methotrexate 12 mg (as the sodium salt), and hydrocortisone 15 mg (as the sodium succinate salt). Each drug combination was added to 12 mL of Elliott’s B solution (NCI), sodium chloride 0.9% (Abbott), dextrose 5% (Abbott), and Ringer’s injection, lactated (Abbott), and stored for 24 hours at 25°C. Cytarabine and methotrexate were both chemically stable, with no drug loss after the full 24 hours in all solutions. Hydrocortisone was also stable in sodium chloride 0.9%, dextrose 5%, and Ringer’s injection, lactated, with about a 2% drug loss. However, in Elliott’s B solution, hydrocortisone was significantly less stable, with a 6% loss in the solution containing 25 mg of hydrocortisone over 24 hours. The solution containing 15 mg of hydrocortisone was worse, with a 5% loss in 10 hours and a 13% loss in 24 hours. The higher pH of Elliott’s B solution and the lower concentration of hydrocortisone may have been factors in this increased decomposition. All mixtures were physically compatible during this study, but a precipitate formed after several days of storage.819
Elliott’s B solution has been recommended as a diluent for cytarabine for intrathecal administration because it is more nearly physiologic.435 The patient’s own spinal fluid also has been recommended.830
Cytarabine (Upjohn) 3 mg/mL diluted in Elliott’s B solution (Orphan Medical) was packaged as 20 mL in 30-mL glass vials and 20-mL plastic syringes (Becton Dickinson) with Red Cap (Burron) Luer-Lok syringe tip caps. The solution was physically compatible and was chemically stable, exhibiting little or no loss during storage for 48 hours at 4 and 23°C.1976
Implantable Pumps
Cytarabine (Upjohn) 1 mg/mL in Elliott’s B solution was evaluated for stability in an implantable infusion pump (Infusaid model 400). In this in vitro assessment, no cytarabine loss occurred in 15 days at 37°C with mild agitation.767
Sorption
Cytarabine (Mack) 0.144 mg/mL in dextrose 5% and in sodium chloride 0.9% exhibited little or no loss due to sorption in polyethylene and polyvinyl chloride (PVC) containers compared to glass containers over 72 hours at room and refrigeration temperatures.2420; 2430
Filtration
Cytarabine 100 mg/15 mL was injected as a bolus through a 0.2-µm nylon, air-eliminating filter (Ultipor, Pall) to evaluate the effect of filtration on simulated intravenous push delivery. Spectrophotometric evaluation showed that about 96% of the drug was delivered through the filter after flushing with 10 mL of sodium chloride 0.9%.809
Cytarabine 10 to 100 mcg/mL exhibited no loss due to sorption to either cellulose nitrate/cellulose acetate ester (Millex OR) or polytetrafluoroethylene (Millex FG) filters.1416
Central Venous Catheter
Cytarabine (Fujisawa) 5 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
For a list of references cited in the text of this monograph, search the monograph titled References.