Drug Detail:Trazimera (Trastuzumab [ tras-too-zoo-mab ])
Generic Name: TRASTUZUMAB 420mg in 20mL;
Dosage Form: injection, kit
Drug Class: HER2 inhibitors
Patient Selection
Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1) and Clinical Studies (14)]. Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using FDA-approved tests specific for breast or gastric cancers by laboratories with demonstrated proficiency. Information on the FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics.
Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using FDA-approved tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers.
Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results.
Recommended Doses and Schedules
- Do not administer as an intravenous push or bolus. Do not mix TRAZIMERA with other drugs.
- Do not substitute TRAZIMERA (trastuzumab-qyyp) for or with ado-trastuzumab emtansine.
Adjuvant Treatment, Breast Cancer
Administer according to one of the following doses and schedules for a total of 52 weeks of TRAZIMERA therapy:
During and following paclitaxel, docetaxel, or docetaxel and carboplatin:
- Initial dose of 4 mg/kg as an intravenous infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly during chemotherapy for the first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel and carboplatin).
- One week following the last weekly dose of TRAZIMERA, administer TRAZIMERA at 6 mg/kg as an intravenous infusion over 30 to 90 minutes every three weeks.
As a single agent within three weeks following completion of multi-modality, anthracycline-based chemotherapy regimens:
- Initial dose at 8 mg/kg as an intravenous infusion over 90 minutes.
- Subsequent doses at 6 mg/kg as an intravenous infusion over 30 to 90 minutes every three weeks [see Dosage and Administration (2.3)].
- Extending adjuvant treatment beyond one year is not recommended [see Adverse Reactions (6.1)].
Important Dosing Considerations
If the patient has missed a dose of TRAZIMERA by one week or less, then the usual maintenance dose (weekly schedule: 2 mg/kg; three-weekly schedule: 6 mg/kg) should be administered as soon as possible. Do not wait until the next planned cycle. Subsequent TRAZIMERA maintenance doses should be administered 7 days or 21 days later according to the weekly or three-weekly schedules, respectively.
If the patient has missed a dose of TRAZIMERA by more than one week, a re-loading dose of TRAZIMERA should be administered over approximately 90 minutes (weekly schedule: 4 mg/kg; three-weekly schedule: 8 mg/kg) as soon as possible. Subsequent TRAZIMERA maintenance doses (weekly schedule: 2 mg/kg; three-weekly schedule 6 mg/kg) should be administered 7 days or 21 days later according to the weekly or three-weekly schedules, respectively.
Infusion Reactions
[See Boxed Warning, Warnings and Precautions (5.2)]
- Decrease the rate of infusion for mild or moderate infusion reactions
- Interrupt the infusion in patients with dyspnea or clinically significant hypotension
- Discontinue TRAZIMERA for severe or life-threatening infusion reactions.
Cardiomyopathy
[See Boxed Warning, Warnings and Precautions (5.1)]
Assess left ventricular ejection fraction (LVEF) prior to initiation of TRAZIMERA and at regular intervals during treatment. Withhold TRAZIMERA dosing for at least 4 weeks for either of the following:
- ≥ 16% absolute decrease in LVEF from pre-treatment values
- LVEF below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values.
TRAZIMERA may be resumed if, within 4 to 8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is ≤ 15%.
Permanently discontinue TRAZIMERA for a persistent (> 8 weeks) LVEF decline or for suspension of TRAZIMERA dosing on more than 3 occasions for cardiomyopathy.
Preparation for Administration
To prevent medication errors, it is important to check the vial labels to ensure that the drug being prepared and administered is TRAZIMERA (trastuzumab-qyyp) and not ado-trastuzumab emtansine.
420 mg Multiple-Dose Vial
Reconstitution
Reconstitute each 420 mg vial of TRAZIMERA with 20 mL of Bacteriostatic Water for Injection (BWFI) containing 1.1% benzyl alcohol as a preservative to yield a multiple-dose solution containing 21 mg/mL trastuzumab-qyyp that delivers 20 mL (420 mg trastuzumab-qyyp). In patients with known hypersensitivity to benzyl alcohol, reconstitute with 20 mL of Sterile Water for Injection (SWFI) without preservative to yield a single use solution.
Use appropriate aseptic technique when performing the following reconstitution steps:
- Using a sterile syringe, slowly inject the 20 mL of diluent into the vial containing the lyophilized powder of TRAZIMERA, which has a cake-like appearance. The reconstituted vial yields a solution for multiple-dose use, containing 21 mg/mL trastuzumab-qyyp.
- Swirl the vial gently to aid reconstitution. DO NOT SHAKE.
- Slight foaming of the product may be present upon reconstitution. Allow the vial to stand undisturbed for approximately 5 minutes.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Inspect visually for particulates and discoloration. The solution should be free of visible particulates, clear to slightly opalescent and colorless to pale yellow-brown.
- Store reconstituted TRAZIMERA in the refrigerator at 2°C to 8°C (36°F to 46°F); discard unused TRAZIMERA after 28 days. If TRAZIMERA is reconstituted with SWFI without preservative, use immediately and discard any unused portion. Do not freeze.
Dilution
- Determine the dose (mg) of TRAZIMERA [see Dosage and Administration (2.2)].
- Calculate the volume of the 21 mg/mL reconstituted TRAZIMERA solution needed.
- Withdraw this amount from the vial and add it to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection, USP. DO NOT USE DEXTROSE (5%) SOLUTION.
- Gently invert the bag to mix the solution.
- The solution of TRAZIMERA for infusion diluted in polyvinylchloride, polyethylene, polypropylene, or ethylene vinyl acetate bags or glass intravenous bottles containing 0.9% Sodium Chloride Injection, USP, should be stored at 2°C to 8°C (36°F to 46°F) for no more than 24 hours prior to use. Do not freeze.
150 mg Single-Dose Vial
Reconstitution
Reconstitute each 150 mg vial of TRAZIMERA with 7.4 mL of Sterile Water for Injection (SWFI) (not supplied) to yield a single-dose solution containing 21 mg/mL trastuzumab-qyyp that delivers 7.15 mL (150 mg trastuzumab-qyyp).
Use appropriate aseptic technique when performing the following reconstitution steps:
- Using a sterile syringe, slowly inject 7.4 mL of SWFI (not supplied) into the vial containing the lyophilized powder of TRAZIMERA, which has a cake-like appearance. The reconstituted vial yields a solution for single-dose use, containing 21 mg/mL trastuzumab-qyyp.
- Swirl the vial gently to aid reconstitution. DO NOT SHAKE.
- Slight foaming of the product may be present upon reconstitution. Allow the vial to stand undisturbed for approximately 5 minutes.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Inspect visually for particulates and discoloration. The solution should be free of visible particulates, clear to slightly opalescent and colorless to pale yellow-brown.
- Use the TRAZIMERA solution immediately following reconstitution with SWFI, as it contains no preservative and is intended for single-dose only. If not used immediately, store the reconstituted TRAZIMERA solution for up to 24 hours at 2°C to 8°C (36°F to 46°F); discard unused TRAZIMERA after 24 hours. Do not freeze.
Dilution
- Determine the dose (mg) of TRAZIMERA [see Dosage and Administration (2.2)].
- Calculate the volume of the 21 mg/mL reconstituted TRAZIMERA solution needed.
- Withdraw this amount from the vial and add it to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection, USP. DO NOT USE DEXTROSE (5%) SOLUTION.
- Gently invert the bag to mix the solution.
- The solution of TRAZIMERA for infusion diluted in polyvinylchloride, polyethylene, polypropylene, or ethylene vinyl acetate bags or glass intravenous bottles containing 0.9% Sodium Chloride Injection, USP, should be stored at 2°C to 8°C (36°F to 46°F) for no more than 24 hours prior to use. Discard after 24 hours. This storage time is additional to the time allowed for the reconstituted vials. Do not freeze.
