Filgrastim (Neupogen) is available as an injection solution in single-dose vials or prefilled syringes.2873 Various filgrastim biosimilars are available: filgrastim-sndz (Zarxio), filgrastim-aafi (Nivestym), filgrastim-ayow (Releuko), and filgrastim-txid (Nypozi).3453; 3623; 3624; 3625 FDA defines a biosimilar as a biological product that is highly similar to an FDA-licensed reference biological with the exception of minor differences in clinically inactive components and for which there are no clinically meaningful differences in safety, purity, or potency.1313 In this monograph, unless otherwise stated, the term “filgrastim products” refers to filgrastim (the reference drug) and its biosimilars.
Filgrastim products are available in prefilled syringes containing 300 mcg/0.5 mL or 480 mcg/0.8 mL.2873; 3453; 3623; 3624; 3625 Filgrastim (Neupogen) and filgrastim-aafi (Nivestym) are also available in single-dose vials containing 300 mcg/1 mL or 480 mcg/1.6 mL.2873; 3623
Inactive ingredients in filgrastim products include sorbitol and polysorbate 80, and may also include sodium acetate or acetic acid, glutamic acid, and/or sodium hydroxide as excipients, in water for injection.2873; 3453; 3623; 3624; 3625 Product labeling should be consulted for specific formulation details.
pH
Filgrastim (Neupogen), filgrastim-ayow (Releuko), filgrastim-txid (Nypozi): 4.2873; 3624; 3625
Filgrastim-sndz (Zarxio): 4.4.3453
Filgrastim-aafi (Nivestym): 3.8 to 4.3.3623
Trade Name(s)
Neupogen, Nivestym, Nypozi, Releuko, Zarxio
Filgrastim products may be administered by subcutaneous injection, intravenous infusion over 15 to 30 minutes, or continuous intravenous infusion.2873; 3453; 3623; 3624; 3625 Filgrastim also has been administered by continuous subcutaneous infusion.2873 Prior to use‚ vials or prefilled syringes should be removed from refrigeration and allowed to reach room temperature for at least 30 minutes but not longer than 24 hours (Neupogen, Nivestym, Releuko, Nypozi)2873; 3623; 3624; 3625 or 8 days (Zarxio).3453
For intravenous infusion, filgrastim products in single-dose vials may be diluted in dextrose 5% to a final concentration not less than 5 mcg/mL.2873; 3623 Filgrastim-sndz (Zarxio) in prefilled syringes may be diluted in dextrose 5% to a final concentration between 5 and 15 mcg/mL.3453 Filgrastim-txid (Nypozi) in prefilled syringes may be diluted in dextrose 5% to a final concentration of 15 mcg/mL.3625 Do not dilute filgrastim products with saline solutions because precipitation may occur.2873; 3453; 3623; 3625 For filgrastim concentrations of 5 to 15 mcg/mL, albumin human should be added to the infusion solution at a final concentration of 2 mg/mL to protect from adsorption of filgrastim to plastic materials.2873; 3453; 3623; 3625 Filgrastim products should not be diluted to concentrations less than 5 mcg/mL.2873; 3453; 3623
Filgrastim products are clear, colorless solutions2873; 3623; 3624 or clear, colorless to slightly yellowish solutions.3453; 3625 Intact containers should be refrigerated at 2 to 8°C in the outer carton to protect from light.2873; 3453; 3623; 3624; 3625 Protect from direct sunlight.2873; 3453; 3623; 3624; 3625 Avoid freezing.2873; 3453; 3623; 3624; 3625 Some manufacturers state if the product is frozen, it may be thawed in the refrigerator prior to administration; however, the product should be discarded if it has been frozen more than once.2873; 3453; 3623 Avoid shaking.2873; 3453; 3623; 3624; 3625
Filgrastim products generally may be stored at room temperature for up to 24 hours and should be discarded after 24 hours at room temperature2873; 3623; 3624; 3625 with the exception of filgrastim-sndz (Zarxio) prefilled syringes, which may be stored at room temperature for up to 8 days and should be discarded after 8 days at room temperature.3453
Diluted solutions of filgrastim (Neupogen) from single-dose vials, filgrastim-aafi (Nivestym) from single-dose vials, or filgrastim-sndz (Zarxio) from prefilled syringes may be stored at room temperature for up to 24 hours, including the time during storage and the duration of the infusion.2873; 3453; 3623
Diluted solutions of filgrastim-txid (Nypozi) may be stored at room temperature for up to 14 hours, which includes time during storage and the duration of the infusion.3625
Freezing Solutions
Freezing should be avoided; however some manufacturers state if the product is frozen, it may be thawed in the refrigerator prior to administration.2873; 3453; 3623 These manufacturers state the product should be discarded if it has been frozen more than once.2873; 3453; 3623
Sorption
Filgrastim (Neupogen), filgrastim-sndz (Zarxio), and filgrastim-aafi (Nivestym), when diluted in dextrose 5% or dextrose 5% with added albumin human as recommended, are stated to be compatible with glass, PVC, polyolefin, and polypropylene containers.2873; 3453; 3623
Filgrastim-txid (Nypozi), when diluted to a concentration of 15 mcg/mL in dextrose 5% with added albumin human as recommended, is stated to be compatible with PVC and polyolefin.3625
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 2 mg/mL to minimize filgrastim adsorption to plastic materials.2873; 3453; 3623; 3624; 3625 Filgrastim products should not be diluted to a final concentration of less than 5 mcg/mL.2873; 3453; 3623; 3624
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.