Filgrastim is available in 300- and 480-mcg vials and syringes with the product compositions and package configurations shown in Table 1.2873
Table 1. Filgrastim Products and Compositions2873
| 300-mcg/1-mL Vial | 480-mcg/1.6-mL Vial | 300-mcg/0.5-mL Syringe | 480-mcg/0.8-mL Syringe | |
|---|---|---|---|---|
| Filgrastim | 300 mcg | 480 mcg | 300 mcg | 480 mcg |
| Acetate | 0.59 mg | 0.94 mg | 0.295 mg | 0.472 mg |
| Sorbitol | 50 mg | 80 mg | 25 mg | 40 mg |
| Polysorbate 80 | 0.004% | 0.004% | 0.004% | 0.004% |
| Sodium | 0.035 mg | 0.056 mg | 0.0175 mg | 0.028 mg |
| Water for injection qs | 1 mL | 1.6 mL | 0.5 mL | 0.8 mL |
Trade Name(s)
Neupogen
Filgrastim is administered by subcutaneous injection undiluted or by intravenous or subcutaneous infusion.4; 2873 For intravenous infusion, it is diluted in 50 to 100 mL of dextrose 5% and given over 15 to 30 minutes, 60 minutes, or 4 hours or over 24 hours by continuous infusion.4; 2873 It may also be given over 24 hours by continuous subcutaneous infusion2873 after diluting the dose in 10 to 50 mL of dextrose 5% and infusing at a rate not exceeding 10 mL/24 hours.4 For extended infusions by either route, a controlled-infusion device is used.4 For filgrastim concentrations of 5 to 15 mcg/mL, albumin human should be added to the infusion solution at a final concentration of 0.2% (2 mg/mL).2873 The drug should not be diluted to concentrations less than 5 mcg/mL.2873
Filgrastim injection is a clear, colorless solution.2873 Intact containers should be refrigerated at 2 to 8°C and protected from direct sunlight.2873 The product also should be protected from freezing2873 and temperatures above 30°C to avoid aggregation.4 The solution should not be shaken since this may damage the drug.2873 If vigorous shaking and subsequent foaming has occurred, the solution should not be used.2873
Although refrigerated storage is required, the manufacturer has stated that filgrastim may be stored at room temperature for up to 24 hours,2873 while others have stated that the drug is stable for 7 days at room temperature.2745 The product is packaged in single-use containers with no antibacterial preservative.2873 The manufacturer recommends that vials not be reentered and that unused portions be discarded.2873
Filgrastim dilutions in dextrose 5% prepared for infusion should be stored under refrigeration and used within 24 hours of preparation because of concern about possible bacterial contamination.4
pH Effects
Filgrastim is stable at pH 3.8 to 4.2, but stability is limited at neutral pH.4
Syringes
Undiluted filgrastim is stable for 24 hours at 15 to 30°C and for 7 days refrigerated at 2 to 8°C repackaged in tuberculin syringes (Becton Dickinson). However, refrigeration and use within 24 hours are recommended because of concern about bacterial contamination.4
Although studies have found filgrastim in syringes remained sterile stored under refrigeration,1764; 2186 the sterility of repackaged injections is a function of the quality of the specific aseptic process of packaging, the quality of the environment in which the sterile product is packaged, and the capability of the personnel involved rather than a property of this unpreserved injection. Consequently, sterility is only valid for the specific facilities and operators for that specific test. The adequacy and safety of repackaging in another location or with other individuals or on another occasion should be verified independently for each institution and batch of repackaged filgrastim injection. Each institution needs to establish specific validation testing results for its own aseptic processing facilities, equipment, procedures, and personnel.1765; 2187 The potential for microbiological growth should be considered when assigning expiration periods.
The sterility of filgrastim 0.2 mL (60 mcg) extemporaneously drawn aseptically into tuberculin syringes and kept under “patient use” storage conditions was evaluated. The syringes were sent home with patients to be stored in their home refrigerators for 7 days and then were returned for sterility testing. A contamination rate as high as 1.25% was reported. The authors expressed the opinion and hope that the high rate of contamination was an artifact of the sterility testing itself. However, contamination during storage in the patients’ refrigerators may have occurred.2294
Sorption
Filgrastim in dextrose 5% at concentrations above 15 mcg/mL and between 2 and 15 mcg/mL with added albumin human 0.2% is compatible with common plastics used in syringes, administration sets, solution containers, and pump cassettes including polyvinyl chloride (PVC), polyolefin, and polypropylene.4
Filgrastim sorption occurs to a greater extent with lower concentrations and with longer infusion tubing.2601 For filgrastim concentrations between 5 and 15 mcg/mL, albumin human should be added to the infusion solution to make a final albumin human concentration of 0.2% (2 mg/mL) to minimize filgrastim adsorption to infusion containers and equipment.4 At filgrastim concentrations above 15 mcg/mL, albumin human is unnecessary.4 The product should not be diluted to a final concentration of less than 5 mcg/mL.2873
The amount of loss of filgrastim (Amgen) from the undiluted injection at a concentration of 300 mcg/mL when delivered through 6.6-French, single-lumen, silicone rubber, Broviac catheters (Bard) was evaluated. The catheters were filled with dextrose 5% (about 0.45 mL) and flushed before and after introduction of the filgrastim. Injected amounts of filgrastim 300 mcg/mL ranged from 0.17 to 1 mL. The delivered flush solution was collected and analyzed for filgrastim content and activity. The lowest volume (0.17 mL) incurred about 32% loss of filgrastim upon delivery. The other volumes incurred lower losses, ranging from 12% to none. A second repeat filgrastim injection incurred similar losses. The filgrastim that was delivered through the catheters remained active.2017
For a list of references cited in the text of this monograph, search the monograph titled References.