HERZUMA

2 DOSAGE AND ADMINISTRATION For intravenous (IV) infusion only. Do not administer as an IV push or bolus. HERZUMA has different dosage and administration instructions than subcutaneous trastuzumab products. ( 2.3 ) Do not substitute HERZUMA (trastuzumab-pkrb) for or with ado-trastuzumab emtansine or fam-trastuzumab deruxtecan. ( 2.3 ) Perform HER2 testing using FDA-approved tests by laboratories with demonstrated proficiency. ( 1 , 2.2 ) Adjuvant Treatment of HER2-Overexpressing Breast Cancer ( 2.2 ) Administer at either: Initial dose of 4 mg/kg over 90 minutes IV infusion, then 2 mg/kg over 30 minutes IV infusion weekly for 12 weeks (with paclitaxel or docetaxel) or 18 weeks (with docetaxel and carboplatin). One week after the last weekly dose of HERZUMA, administer 6 mg/kg as an IV infusion over 30 to 90 minutes every three weeks to complete a total of 52 weeks of therapy, or Initial dose of 8 mg/kg over 90 minutes IV infusion, then 6 mg/kg over 30 to 90 minutes IV infusion every three weeks for 52 weeks. Metastatic HER2-Overexpressing Breast Cancer ( 2.3 ) Initial dose of 4 mg/kg as a 90 minutes IV infusion followed by subsequent weekly doses of 2 mg/kg as 30 minutes IV infusions. Metastatic HER2-Overexpressing Gastric Cancer ( 2.3 ) Initial dose of 8 mg/kg over 90 minutes IV infusion, followed by 6 mg/kg over 30 to 90 minutes IV infusion every 3 weeks. 2.1 Evaluation and Testing Before Initiating HERZUMA Assess left ventricular ejection fraction (LVEF) prior to initiation of HERZUMA and at regular intervals during treatment. [see Boxed Warning , Dosage and Administration (2.5) , Warnings and Precautions (5.1) ] . Verify the pregnancy status of females of reproductive potential prior to the initiation of HERZUMA [see Warnings and Precautions (5.3) , Use in Specific Populations ( 8.1 , 8.3 )]. 2.2 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. 2.3 Recommended Dosage HERZUMA is for intravenous infusion only. Do not administer as an intravenous push or bolus. HERZUMA has different dosage and administration instructions than subcutaneous trastuzumab products. Do not mix HERZUMA with other drugs. Do not substitute HERZUMA (trastuzumab-pkrb) for or with ado-trastuzumab emtansine or fam-trastuzumab deruxtecan. Adjuvant Treatment of Breast Cancer Administer according to one of the following doses and schedules for a total of 52 weeks of HERZUMA 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 HERZUMA, administer HERZUMA 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 . Extending adjuvant treatment beyond one year is not recommended [see Adverse Reactions (6.1) ]. Metastatic Breast Cancer Administer HERZUMA, alone or in combination with paclitaxel, at an initial dose of 4 mg/kg as a 90-minute intravenous infusion followed by subsequent once weekly doses of 2 mg/kg as 30-minute intravenous infusions until disease progression. Metastatic Gastric Cancer Administer HERZUMA at an initial dose of 8 mg/kg as a 90-minute intravenous infusion followed by subsequent doses of 6 mg/kg as an intravenous infusion over 30 to 90 minutes every three weeks until disease progression . 2.4 Important Dosing Considerations Missed Dose If the patient has missed a dose of HERZUMA by one week or less, then the usual maintenance dose (weekly schedule: 2 mg/kg; once every three week schedule: 6 mg/kg) should be administered as soon as possible. Do not wait until the next planned cycle. Subsequent HERZUMA maintenance doses should be administered 7 days or 21 days later according to the weekly or once every three week schedules, respectively. If the patient has missed a dose of HERZUMA by more than one week, a re-loading dose of HERZUMA should be administered over approximately 90 minutes (weekly schedule: 4 mg/kg; once every three week schedule: 8 mg/kg) as soon as possible. Subsequent HERZUMA maintenance doses (weekly schedule: 2 mg/kg; once every three week schedule 6 mg/kg) should be administered 7 days or 21 days later according to the weekly or once every three week schedules, respectively. 2.5 Dosage Modifications for Adverse Reactions 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 HERZUMA 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 HERZUMA and at regular intervals during treatment. Withhold HERZUMA 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. HERZUMA 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 HERZUMA for a persistent (> 8 weeks) LVEF decline or for suspension of HERZUMA dosing on more than 3 occasions for cardiomyopathy. 2.6 Preparation Instructions To prevent medication errors, it is important to check the vial labels to ensure that the drug being prepared and administered is HERZUMA (trastuzumab-pkrb) and not ado-trastuzumab emtansine or fam-trastuzumab deruxtecan. 420 mg Multiple-dose vial Reconstitution Reconstitute each 420 mg vial of HERZUMA with 20 mL of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative to yield a multiple-dose solution containing 21 mg/mL trastuzumab-pkrb that delivers 20 mL (420 mg trastuzumab-pkrb). In patients with known hypersensitivity to benzyl alcohol, reconstitute with 20 mL of Sterile Water for Injection (SWFI) without preservative to yield a one-time 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 HERZUMA, which has a cake-like appearance. The stream of diluent should be directed into the cake. The reconstituted vial yields a solution for multiple-dose use, containing 21 mg/mL trastuzumab-pkrb. 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. Store reconstituted HERZUMA in the refrigerator at 2°C to 8°C (36°F to 46°F); discard unused HERZUMA after 28 days. If HERZUMA is reconstituted with SWFI without preservative, use immediately and discard any unused portion. Do not freeze. Dilution Determine the dose (mg) of HERZUMA [see Dosage and Administration (2.3) ] . Calculate the volume of the 21 mg/mL reconstituted HERZUMA solution needed, withdraw this amount from the vial using a sterile needle and syringe 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 HERZUMA for infusion diluted in polyvinylchloride or polyethylene bags 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. This storage time is additional to the time allowed for the reconstituted vials. Do not freeze. 150 mg Single-dose vial Reconstitution Reconstitute each 150 mg vial of HERZUMA with 7.4 mL of Sterile Water for Injection (SWFI) (not supplied) to yield a single-dose solution containing 21 mg/mL trastuzumab-pkrb that delivers 7.15 mL (150 mg trastuzumab-pkrb). 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 HERZUMA, which has a cake-like appearance. The stream of diluent should be directed into the cake. The reconstituted vial yields a solution containing 21 mg/mL trastuzumab-pkrb. 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. Use the HERZUMA solution immediately following reconstitution with SWFI, as it contains no preservative and is intended for one-time use only. If not used immediately, store the reconstituted HERZUMA solution for up to 24 hours at 2°C to 8°C (36°F to 46°F); discard any unused HERZUMA after 24 hours. Do not freeze. Dilution Determine the dose (mg) of HERZUMA [see Dosage and Administration (2.3) ] . Calculate the volume of the 21 mg/mL reconstituted HERZUMA solution needed. Withdraw this amount from the vial using a sterile needle and syringe 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 HERZUMA for infusion diluted in polyvinylchloride or polyethylene bags 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.

See official label

1 INDICATIONS AND USAGE HERZUMA is a HER2/neu receptor antagonist indicated in adults for: the treatment of HER2-overexpressing breast cancer.