Herceptin® (Trastuzumab)

Trastuzumab - Herceptin®

Usual Diluents

Dilution Data

Preparation for Administration
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Reconstitution:  Reconstitute each 440 mg vial of Herceptin with 20 mL of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative to yield a multi-dose solution containing 21 mg/mL trastuzumab. 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 cake of Herceptin. The stream of diluent should be directed into the lyophilized cake. 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 Herceptin at 2—8° C; discard unused Herceptin after 28 days. If Herceptin is reconstituted with SWFI without preservative, use immediately and discard any unused portion. Dilution
Determine the dose (mg) of Herceptin - see Dosage and Administration. Calculate the volume of the 21 mg/mL reconstituted Herceptin 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
ADMINISTRATION: Initial doses (loading), are infused over 90 minutes.  Subsequent doses are infused over 30 to 60 minutes if tolerated. See Dosage and administration for additional info.

Stability and Storage:  Vials of Herceptin are stable at 2–8°C (36–46°F) prior to reconstitution.  Do not use beyond the expiration date stamped on the vial. A vial of Herceptin reconstituted with BWFI, as supplied, is stable for 28 days after reconstitution when stored refrigerated at 2–8°C (36–46°F). Discard any remaining multi-dose reconstituted solution after 28 days. A vial of Herceptin reconstituted with unpreserved SWFI (not supplied) should be used immediately and any unused portion discarded. Do Not Freeze Herceptin following reconstitution or dilution.    The solution of Herceptin for infusion diluted in polyvinylchloride or polyethylene bags containing 0.9% Sodium Chloride Injection, USP, should be stored at 2–8°C (36–46°F) for no more than 24 hours prior to use.

CLINICAL PHARMACOLOGY

Mechanism of Action
The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Herceptin has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2.

Herceptin is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro, Herceptin-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.

INDICATIONS AND USAGE

1.1 Adjuvant Breast Cancer
Herceptin is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see PACKAGE INSERT for Clinical Studies ( 14.1)]) breast cancer  as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel  with docetaxel and carboplatin  As a single agent following multi-modality anthracycline based therapy. 1.2 Metastatic Breast Cancer
Herceptin is indicated:  In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease. 2.  DOSAGE AND ADMINISTRATION

2.1 Recommended Doses and Schedules
Do not administer as an intravenous push or bolus. Do not mix Herceptin with other drugs

Adjuvant Treatment, Breast Cancer:

Administer according to one of the following doses and schedules for a total of 52 weeks of Herceptin therapy:

During and following paclitaxel, docetaxel, or docetaxel/carboplatin:
Initial dose of 4mg/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/carboplatin). One week following the last weekly dose of Herceptin, administer Herceptin at 6 mg/kg as an intravenous infusion over 30-60 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-minutes every three weeks. Metastatic Treatment, Breast Cancer: Administer Herceptin, 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. 2.2 Dose Modifications
Infusion Reactions:

[see Boxed Warning, and PACKAGE INSERT for 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 Herceptin for severe or life-threatening infusion reactions Cardiomyopathy:
[see Boxed Warning, and PACKAGE INSERT for Warnings and Precautions ( 5.1)].

Assess left ventricular ejection fraction (LVEF) prior to initiation of Herceptin and at regular intervals during treatment. Withhold Herceptin 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 Herceptin may be resumed if, within 4-8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is ≤ 15%.

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

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2.3 Preparation for Administration
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Reconstitution

Reconstitute each 440 mg vial of Herceptin with 20 mL of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative to yield a multi-dose solution containing 21 mg/mL trastuzumab. 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 cake of Herceptin. The stream of diluent should be directed into the lyophilized cake. 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 Herceptin at 2—8° C; discard unused Herceptin after 28 days. If Herceptin is reconstituted with SWFI without preservative, use immediately and discard any unused portion.
Dilution
Determine the dose (mg) of Herceptin [see Dosage and Administration ( 2.1)]. Calculate the volume of the 21 mg/mL reconstituted Herceptin 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 3.  DOSAGE FORMS AND STRENGTHS
440 mg lyophilized powder per multi-use vial.

4. CONTRAINDICATIONS
None.

HOW SUPPLIED/STORAGE AND HANDLING

How Supplied
Herceptin is supplied in a multi-use vial containing 440 mg trastuzumab as a lyophilized sterile powder, under vacuum. Each carton contains one vial Herceptin® and one vial (20 mL) of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative. NDC 50242-134-68.

Stability and Storage
Vials of Herceptin are stable at 2–8°C (36–46°F) prior to reconstitution.

Do not use beyond the expiration date stamped on the vial. A vial of Herceptin reconstituted with BWFI, as supplied, is stable for 28 days after reconstitution when stored refrigerated at 2–8°C (36–46°F). Discard any remaining multi-dose reconstituted solution after 28 days. A vial of Herceptin reconstituted with unpreserved SWFI (not supplied) should be used immediately and any unused portion discarded. Do Not Freeze Herceptin following reconstitution or dilution.

The solution of Herceptin for infusion diluted in polyvinylchloride or polyethylene bags containing 0.9% Sodium Chloride Injection, USP, should be stored at 2–8°C (36–46°F) for no more than 24 hours prior to use.