Cladribine is available as a 1-mg/mL concentrate for injection in single-use preservative-free vials containing 10 mL of the concentrate.2938 Each mL of the solution contains cladribine 1 mg, sodium chloride 9 mg, and phosphoric acid and/or dibasic sodium phosphate to adjust the pH.2938 The injection is a concentrate that must be diluted for administration.2938
pH
From 5.5 to 8.2938
Tonicity
Cladribine injection is isotonic.2938
Sodium Content
Each mL of cladribine injection contains 0.15 mEq of sodium.2938
Cladribine is administered by continuous intravenous infusion over 24 hours after dilution in 500 mL of sodium chloride 0.9% for repeated single daily doses.2938 Some manufacturers recommend that the injection be passed through a 0.22-µm filter prior to being introduced into the infusion bag in the preparation of single daily doses.2938
Alternatively, to prepare a solution for 7-day continuous infusion, cladribine should be diluted only in bacteriostatic sodium chloride 0.9% containing benzyl alcohol 0.9%.2938 The 7-day solution should be prepared by sequentially transferring the volume of the total 7-day dose followed by the calculated volume of solution required to bring the final volume to 100 mL to the pump reservoir through a 0.22-µm hydrophilic syringe filter.2938 Air in the reservoir should be removed by aspiration using a syringe and a new filter or a vent-filter assembly.2938 The finished preserved solution is then administered continuously over 7 days.2938
The use of dextrose 5% as a diluent is not recommended because of an increased rate of cladribine degradation.2938
Intact cladribine vials should be stored under refrigeration and protected from light.2938 The solution is clear and colorless.2938
Solutions prepared for a single daily dose are stated to be both physically and chemically stable at room temperature under normal lighting conditions for at least 24 hours in polyvinyl chloride (PVC) containers; however, the manufacturers recommend that diluted solutions of cladribine be administered promptly or stored under refrigeration for no more than 8 hours prior to administration.2938
A precipitate may develop upon low-temperature storage; the precipitate may be redissolved by allowing the solution to warm to room temperature with vigorous shaking.2938 Heating the solution is not recommended.2938 However, less than 5% loss of activity is reported to occur in 7 days when the solution is stored at 37°C.1369
Freezing does not adversely affect stability of the product.2938 Thawing should be allowed to occur naturally by exposure to room temperature.2938 The vials should not be heated or exposed to microwaves.2938 After thawing, the vial contents are stable under refrigeration until expiration.2938 Thawed vials should not be refrozen.2938
Cladribine (Ortho Biotech) 0.025 mg/mL in sodium chloride 0.9% did not exhibit an antimicrobial effect on Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans inoculated into the solution. Admixtures should be stored under refrigeration whenever possible, and the potential for microbiological growth should be considered when assigning expiration periods.2160
Ambulatory Pumps
Prepared in bacteriostatic sodium chloride 0.9% preserved with benzyl alcohol 0.9%, cladribine exhibits both chemical and physical stability for at least 7 days in Sims Deltec ambulatory infusion pump reservoirs.2938 Preservative effectiveness may be reduced in solutions prepared for patients weighing more than 85 kg due to greater benzyl alcohol dilution in such patients.2938 In solutions of cladribine at concentrations of 0.15 to 0.3 mg/mL in bacteriostatic sodium chloride 0.9% containing benzyl alcohol, the drug is stated to be stable for at least 14 days.1369
For a list of references cited in the text of this monograph, search the monograph titled References.