Trastuzumab is available as a lyophilized powder in multiple-use vials containing 440 mg of the drug with a,a-trehalose dihydrate 400 mg, L-histidine hydrochloride 9.9 mg, L-histidine 6.4 mg, and polysorbate 20 1.8 mg; the vial is sealed under a vacuum.3086 Each vial of trastuzumab is packaged with a 20-mL vial of bacteriostatic water for injection diluent containing benzyl alcohol 1.1% as a preservative.3086
CAUTION: Care should be taken to ensure that the correct drug product is prepared and that no confusion with other products (e.g., ado-trastuzumab emtansine) occurs.3086 Each vial of trastuzumab should be reconstituted with 20 mL of the provided bacteriostatic water for injection to yield a multiple-use solution containing trastuzumab 21 mg/mL.3086 The drug also may be reconstituted with 20 mL of sterile water for injection (without preservative) to yield a single-use solution containing trastuzumab 21 mg/mL.3086 The diluent should be slowly injected into the vial, directing the stream of diluent into the lyophilized cake.3086 The vial should be swirled gently to aid reconstitution; shaking should be avoided.3086 The vial should be allowed to stand undisturbed for approximately 5 minutes as slight foaming of the product may occur upon reconstitution.3086 The reconstituted solution should be visually inspected for particulate matter and discoloration; the solution should be free of visible particulates.3086
The appropriate dose of the reconstituted solution should be diluted in 250 mL of sodium chloride 0.9% in a polyvinyl chloride (PVC) or polyethylene bag;3086 dextrose 5% should not be used due to the potential risk of protein aggregation.3086; 3088 The infusion bag should be gently inverted to mix the diluted solution.3086
pH
The pH of the reconstituted solution is approximately 6.3086
Trade Name(s)
Herceptin
CAUTION: Care should be taken to ensure that the correct drug product is administered and that no confusion with other products (e.g., ado-trastuzumab emtansine) occurs.3086 Trastuzumab is administered only by intravenous infusion following reconstitution and further dilution in 250 mL of sodium chloride 0.9%.3086 The drug should be infused over 30 to 90 minutes depending upon previous trastuzumab exposure and the indication for the drug in the specific patient.3086 Trastuzumab should not be administered by intravenous push or bolus injection.3086
Intact vials of trastuzumab are stable at 2 to 8°C.3086 Trastuzumab is a white to pale yellow lyophilized powder that forms a clear to slightly opalescent and colorless to pale yellow solution upon reconstitution.3086
When reconstituted with the provided bacteriostatic water for injection diluent, vials of the reconstituted multiple-use solution are stable for 28 days if stored at 2 to 8°C; any solution remaining after 28 days should be discarded.3086 Vials of trastuzumab reconstituted with unpreserved sterile water for injection should be used immediately; any unused portions should be discarded.3086 The manufacturer states that trastuzumab should not be mixed with other drugs.3086
Diluted trastuzumab infusion solutions should be stored at 2 to 8°C for no longer than 24 hours prior to use.3086 Although trastuzumab solutions diluted to concentrations of 0.4, 1, or 4 mg/mL (diluent unspecified) were reported to be physically stable with no change in monomer concentration for up to 28 days when stored at 2 to 8°C, biological activity was not reported in this study.3089
Reconstituted solutions or solutions diluted for infusion should not be frozen.3086
Temperature Effects
In a study evaluating the physical stability of trastuzumab, solutions containing trastuzumab (Roche) 0.4 or 4 mg/mL (diluent unspecified) showed no increase in particle size up to a temperature of 65°C.3089 At 75°C, the solutions became turbid, suggesting the formation of insoluble aggregates; following centrifugation, particle size analysis also revealed soluble aggregates within the clear supernatant.3089 Additional spectrophotometric evaluation showed a loss of ordered structure of the drug at temperatures of 75°C.3089
Filtration
Use of an inline filter was not required for administration of trastuzumab-containing solutions in clinical studies.3087 The manufacturer makes no recommendations regarding filtration of the drug.3086
For a list of references cited in the text of this monograph, search the monograph titled References.