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Drug: Trastuzumab - Herceptin®

Usual Diluents

Dilution Data

DILUTION SUMMARY

[Amount of drug] [Infusion volume] [Infusion rate]

[Prescribed dose ] [250 ml NS] [ 90 minutes]*

*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. DO NOT SHAKE.

Preparation for Administration
------------------------------------------------------
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.

Stability / Miscellaneous

WARNINGS	CLINICAL PHARMACOLOGY	INDICATIONS
CONTRAINDICATIONS	DOSAGE AND ADMINISTRATION	RECONSTITUTION / DILUTION
	HOW SUPPLIED
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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.

WARNINGS
CARDIOMYOPATHY, INFUSION REACTIONS, AND PULMONARY TOXICITY

Cardiomyopathy

Herceptin can result in sub-clinical and clinical cardiac failure manifesting as CHF and decreased LVEF. The incidence and severity of left ventricular cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracycline containing chemotherapy regimens.

Evaluate left ventricular function in all patients prior to and during treatment with Herceptin. Discontinue Herceptin treatment in patients receiving adjuvant therapy and strongly consider discontinuation of Herceptin treatment in patients with metastatic breast cancer for clinically significant decrease in left ventricular function. [see PACKAGE INSERT for Warnings and Precautions ( 5.1) and Dosage and Administration ( 2.2)]

Infusion Reactions; Pulmonary Toxicity

Herceptin administration can result in serious infusion reactions and pulmonary toxicity. Fatal infusion reactions have been reported. In most cases, symptoms occurred during or within 24 hours of administration of Herceptin. Herceptin infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension. Patients should be monitored until signs and symptoms completely resolve. Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. [see PACKAGE INSERT for Warnings and Precautions ( 5.2, 5.4)]

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.

------------------------------------------------------
2.3 Preparation for Administration
------------------------------------------------------
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.

Reference(s)

1) [PACKAGE INSERT DATA] : Herceptin (Trastuzumab) kit for intravenous use. [Genentech] Genentech, Inc. 1 DNA Way. South San Francisco, CA 94080-4990. Revised: 06/2008.

Drug: Trastuzumab - Herceptin®

Usual Diluents

Dilution Data

DILUTION SUMMARY

[Amount of drug] [Infusion volume] [Infusion rate]

Stability / Miscellaneous

Reference(s)

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