Bortezomib is available as a lyophilized powder (Velcade, Janssen/Takeda; generic) in single-dose vials containing bortezomib 1, 2.5, or 3.5 mg of drug with mannitol 10, 25, or 35 mg, respectively.2897; 3768 Reconstitute only with sodium chloride 0.9% to a final concentration based on the intended route of administration according to Table 1.2897; 3768 For intravenous bolus injection, reconstitute to a final concentration of 1 mg/mL.2897; 3768 For subcutaneous administration, reconstitute to a final concentration of 2.5 mg/mL; however, if the 2.5-mg/mL concentration results in subcutaneous injection site reactions, a 1-mg/mL solution also may be administered subcutaneously.2897; 3768
Table 1. Reconstitution Volumes for Bortezomib Lyophilized Powder for Intravenous and Subcutaneous Administration2897; 3768
| Route of Administration | Bortezomib Vial Content | Volume of Diluent (sodium chloride 0.9%) | Final Bortezomib Concentration |
|---|---|---|---|
| Intravenous | 1 mg | 1 mL | 1 mg/mLb |
| Intravenous | 2.5 mg | 2.5 mL | 1 mg/mLb |
| Intravenous | 3.5 mg | 3.5 mL | 1 mg/mLb |
| Subcutaneous | 1 mg | 0.4 mL | 2.5 mg/mLa |
| Subcutaneous | 2.5 mg | 1 mL | 2.5 mg/mL |
| Subcutaneous | 3.5 mg | 1.4 mL | 2.5 mg/mL |
aActual vial content results in a final concentration of 1 mg/0.4 mL.bMay also be administered by subcutaneous injection.
Bortezomib is also available as a 2.5-mg/mL injection solution (Boruzu, Amneal) in single-dose vials containing 3.5 mg of bortezomib in 1.4 mL.4040 Each mL contains bortezomib 2.5 mg, mannitol 25 mg, and sodium chloride in water for injection.4040 The contents of the vial may be diluted with 2.1 mL of sodium chloride 0.9% to yield a concentration of 1 mg/mL.4040
Trade Name(s)
Velcade, Boruzu
Bortezomib is administered by intravenous bolus injection over 3 to 5 seconds or by subcutaneous injection.2897; 3768; 4040 It should not be given by any other route.2897; 3768; 4040 Inadvertent intrathecal administration of bortezomib has resulted in fatalities and administration by this route is contraindicated.2897; 2898; 3768; 4040
Because the concentration of bortezomib for subcutaneous administration (2.5 mg/mL) is greater than the diluted concentration of bortezomib for intravenous administration (1 mg/mL), the manufacturer-provided sticker indicating the route of administration should be placed directly on the syringe once the required dose has been withdrawn from the vial.2897; 3768; 4040
Bortezomib lyophilized powder in intact vials should be stored at controlled room temperature in the original package to protect from light.2897 The lyophilized powder is a white to off-white powder or cake that forms a clear, colorless solution upon reconstitution.2897
The manufacturer states that reconstituted solutions may be stored at 25°C in the original vial or in a syringe under normal room light and should be used within 8 hours of preparation.2897 However, bortezomib (Janssen-Cilag) reconstituted to a concentration of 1 mg/mL in the original vials was reported to be stable for at least 5 days under refrigeration protected from light.2663 In another study, bortezomib reconstituted to a concentration of 1 mg/mL in the original vials was found to undergo little or no loss for 42 days stored at 23°C or refrigerated at 4°C.2768
Reconstituted to a concentration of 2.5 mg/mL, bortezomib (Janssen) was found to undergo less than 5% loss in 21 days when stored in the original vial at 23°C in fluorescent light or under refrigeration at 4°C in the dark.2972 In another study, bortezomib (Janssen-Cilag), reconstituted to a concentration of 2.5 mg/mL in the original vial and protected from light, was stable (less than 5% loss) for 7 days at 2 to 8°C or 24 hours at 20 to 30°C.4042
Bortezomib lyophilized powder from several different manufacturers (Teva, Actavis, Dr. Reddy’s Laboratories, Apotex, and MDA/Juno) was reconstituted to a concentration of 1 or 2.5 mg/mL and kept in the original vials or packaged in polypropylene syringes.4041 All of the reconstituted solutions were stored protected from light at either 21 to 27°C (room temperature) or 4°C for, depending on the manufacturer, up to 21 days (Actavis, Dr. Reddy's), 42 days (Apotex, Teva), or 84 days (MDA/Juno).4041 Throughout the study, all solutions remained clear and colorless with no visible particles.4041 The minimum calculated time to 10% loss across all products was at least 35 days for solutions stored at 4°C, or 25 days for solutions stored at room temperature; however, most solutions were stable for longer periods of time.4041
Bortezomib (Janssen-Cilag) reconstituted to a concentration of 1 mg/mL did not result in the loss of viability of Staphylococcus aureus within 120 hours at room temperature. Diluted solutions should be stored under refrigeration whenever possible, and the potential for microbiological growth should be considered when assigning expiration periods.2740
Bortezomib injection solution in intact vials should be stored at 2 to 8°C in the original package to protect from light.4040 Bortezomib injection solution is a clear to light yellow solution.4040 The manufacturer states diluted solutions should be clear and colorless and may be stored in the original vial or in a syringe under normal room light at room temperature (20 to 25°C) for up to 8 hours.4040
Syringes
Reconstituted bortezomib (Janssen-Cilag) 1 mg/mL was packaged in 5-mL polypropylene plastic syringes (Becton-Dickinson) and stored at room temperature exposed to neon light and under refrigeration in the dark. The drug solutions remained clear and colorless throughout the study at both temperatures. About 8 to 9% loss occurred in 5 days at room temperature and in 7 days refrigerated and protected from light.2663
Reconstituted bortezomib (Janssen) 2.5 mg/mL was packaged in 3-mL polypropylene syringes and stored at 23°C in fluorescent light or under refrigeration at 4°C in the dark.2972 Less than 5% loss occurred in 21 days in syringes stored at either temperature.2972 In another study, reconstituted bortezomib (Janssen-Cilag) 2.5 mg/mL packaged in polypropylene syringes, protected from light, was stable (less than 5% loss) for 7 days at 2 to 8°C or 24 hours at 20 to 30°C.4042
The stability of reconstituted bortezomib 1 and 2.5 mg/mL solutions from 5 different manufacturers in polypropylene syringes was evaluated.4041 Reconstituted solutions of bortezomib manufactured by Teva, Actavis, or Dr. Reddy's Laboratories were packaged in 3-mL polypropylene syringes (Becton Dickinson).4041 Reconstituted solutions of bortezomib manufactured by Apotex or MDA/Juno were packaged in 3-mL polypropylene closed system transfer syringes (Equashield).4041 All of the reconstituted solutions were stored protected from light at either 21 to 27°C (room temperature) or 4°C for, depending on the manufacturer, up to 21 days (Actavis, Dr. Reddy's), 42 days (Apotex, Teva), or 84 days (MDA/Juno).4041 Throughout the study, all solutions remained clear and colorless with no visible particles.4041 The minimum calculated time to 10% loss across all products was at least 35 days for solutions stored at 4°C, or 25 days for solutions stored at room temperature; however, most solutions were stable for longer periods of time.4041
For a list of references cited in the text of this monograph, search the monograph titled References.