HERCESSI Solution for injection Ref.[109764] Active ingredients: Trastuzumab

2.1 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.

2.2 Recommended Doses and Schedules

• Do not administer as an intravenous push or bolus. Do not mix Hercessi with other drugs.
• Do not substitute Hercessi (trastuzumab-strf) 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 Hercessi 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 Hercessi, administer Hercessi at 6 mg/kg as an intravenous infusion over 30−90 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 30−90 minutes every three weeks [see Dosage and Administration (2.3)].
• Extending adjuvant treatment beyond one year is not recommended [see Adverse Reactions (6.1)].

Metastatic Treatment, Breast Cancer

• Administer Hercessi, 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 Hercessi 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 30–90 minutes every three weeks until disease progression [see Dosage and Administration (2.3)].

2.3 Important Dosing Considerations

If the patient has missed a dose of Hercessi 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 Hercessi 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 Hercessi by more than one week, a re-loading dose of Hercessi should be administered over approximately 90 minutes (weekly schedule: 4 mg/kg; three- weekly schedule: 8 mg/kg) as soon as possible. Subsequent Hercessi 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 Hercessi 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 Hercessi and at regular intervals during treatment. Withhold Hercessi 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.

Hercessi may be resumed if, within 4−8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is ≤ 15%.

Permanently discontinue Hercessi for a persistent (> 8 weeks) LVEF decline or for suspension of Hercessi dosing on more than 3 occasions for cardiomyopathy.

2.4 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 Hercessi (trastuzumab-strf) and not ado-trastuzumab emtansine.

150 mg Single-dose vial

Reconstitution:

Reconstitute each 150 mg vial of Hercessi with 7.4 mL of Sterile Water for Injection (SWFI) (not supplied) to yield a single-dose solution containing 21 mg/mL trastuzumab-strf that delivers 7.15 mL (150 mg trastuzumab-strf).

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 Hercessi, 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-strf.
• 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 Hercessi 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 Hercessi solution for up to 24 hours at 2⁰C to 8⁰C (36⁰F to 46⁰F); discard any unused Hercessi after 24 hours. Do not freeze. Protect the reconstituted solution from light.

Dilution:

• Determine the dose (mg) of Hercessi [see Dosage and Administration (2.1)].
• Calculate the volume of the 21 mg/mL reconstituted Hercessi solution needed.
• Withdraw this amount from the vial and add it to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection. DO NOT USE DEXTROSE (5%) SOLUTION.
• Gently invert the bag to mix the solution. Do not shake.
• The solution of Hercessi for infusion diluted in infusion bags made of polypropylene (PP) only containing 0.9% Sodium Chloride Injection, should be stored at 2°C to 8°C (36°F to 46°F) for no more than 24 hours or at 30°C to 35°C (86°F to 95°F) for no more than 6 hours prior to use. Discard any unused Hercessi after 24 hours when stored at 2°C to 8°C (36°F to 46°F) or after 6 hours when stored at 30°C to 35°C (86°F to 95°F). This storage time is additional to the time allowed for the reconstituted vials. Do not freeze.

There is no experience with overdosage in human clinical trials. Single doses higher than 8 mg/kg have not been tested.

Store Hercessi vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton until time of reconstitution. Do not freeze. Do not shake.