OGIVRI: Package Insert and Label Information

OGIVRI- trastuzumab
OGIVRI- trastuzumab injection, powder, lyophilized, for solution
Mylan Institutional LLC

1 INDICATIONS AND USAGE

1.1 Adjuvant Breast Cancer

Ogivri is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies (14.1)]) breast cancer

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as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel

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as part of a treatment regimen with docetaxel and carboplatin

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as a single agent following multi-modality anthracycline based therapy.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product [see Dosage and Administration (2.1)].

1.2 Metastatic Breast Cancer

Ogivri is indicated:

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In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer

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As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product [see Dosage and Administration (2.1)].

1.3 Metastatic Gastric Cancer

Ogivri is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product [see Dosage and Administration (2.1)].

2 DOSAGE AND ADMINISTRATION

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

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Do not administer as an intravenous push or bolus. Do not mix Ogivri with other drugs.

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Do not substitute Ogivri (trastuzumab-dkst) 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 Ogivri therapy:

During and following paclitaxel, docetaxel, or docetaxel and carboplatin:

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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).

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One week following the last weekly dose of Ogivri, administer Ogivri 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:

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Initial dose at 8 mg/kg as an intravenous infusion over 90 minutes

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Subsequent doses at 6 mg/kg as an intravenous infusion over 30 to 90 minutes every three weeks [see Dosage and Administration (2.3)].

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Extending adjuvant treatment beyond one year is not recommended [see Adverse Reactions (6.1)].

Metastatic Treatment, Breast Cancer:

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Administer Ogivri, 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:

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Administer Ogivri 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 [see Dosage and Administration (2.3)].

2.3 Important Dosing Considerations

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

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Decrease the rate of infusion for mild or moderate infusion reactions

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Interrupt the infusion in patients with dyspnea or clinically significant hypotension

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Discontinue Ogivri 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 Ogivri and at regular intervals during treatment. Withhold Ogivri dosing for at least 4 weeks for either of the following:

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≥16% absolute decrease in LVEF from pre-treatment values

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LVEF below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values.

Ogivri 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 Ogivri for a persistent (>8 weeks) LVEF decline or for suspension of Ogivri 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 Ogivri (trastuzumab-dkst) and not ado-trastuzumab emtansine.

420 mg Multiple-dose vial supplied with a separate vial containing 20 mL of Bacteriostatic Water for Injection, USP, to be used as diluent.

420 mg Multiple-dose vial drug only carton. No diluent is provided.

Reconstitution

​Reconstitute each 420 mg vial of Ogivri with 20 mL of Bacteriostatic Water for Injection, USP (BWFI), containing 0.9% to 1.1% benzyl alcohol (not supplied for the 420 mg multiple-dose vial drug only carton) as a preservative to yield a multiple-dose solution containing 21 mg/mL trastuzumab-dkst that delivers 20 mL (420 mg trastuzumab-dkst). In patients with known hypersensitivity to benzyl alcohol, reconstitute with 20 mL of Sterile Water for Injection, USP (SWFI) without preservative to yield a one time use solution.

Use appropriate aseptic technique when performing the following reconstitution steps:

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Using a sterile syringe, slowly inject the 20 mL of diluent into the vial containing the lyophilized powder of Ogivri, which has a cake-like appearance. The stream of diluent should be directed into the lyophilized cake. The reconstituted vial yields a solution for multiple-dose use, containing 21 mg/mL trastuzumab-dkst.

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Swirl the vial gently to aid reconstitution. DO NOT SHAKE.

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Slight foaming of the product may be present upon reconstitution. Allow the vial to stand undisturbed for approximately 5 minutes.

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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.

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Store reconstituted Ogivri in the refrigerator at 2° to 8°C (36° to 46°F); discard unused Ogivri after 28 days. If Ogivri is reconstituted with SWFI without preservative, use immediately and discard any unused portion. Do not freeze.

Dilution

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Determine the dose (mg) of Ogivri [see Dosage and Administration (2.1)]. Calculate the volume of the 21 mg/mL reconstituted Ogivri solution needed.

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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.

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Gently invert the bag to mix the solution.

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The solution of Ogivri for infusion diluted in polyvinylchloride or polyethylene bags containing 0.9% Sodium Chloride Injection, USP, should be stored at 2° to 8°C (36° 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 Ogivri with 7.4 mL of Sterile Water for Injection (SWFI) (not supplied) to yield a single-dose solution containing 21 mg/mL trastuzumab-dkst that delivers 7.15 mL (150 mg trastuzumab-dkst).

​ Use appropriate aseptic technique when performing the following reconstitution steps:

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Using a sterile syringe, slowly inject the 7.4 mL of SWFI (not supplied) into the vial containing the lyophilized powder of Ogivri, which has a cake-like appearance. The stream of diluent should be directed into the cake. The reconstituted vial yields a solution for single-dose use, containing 21 mg/mL trastuzumab-dkst.

•

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.

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Use the Ogivri 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 Ogivri solution for up to 24 hours at 2° to 8°C (36° to 46°F); discard any unused Ogivri after 24 hours. Do not freeze .

Dilution

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Determine the dose (mg) of Ogivri [see Dosage and Administration (2.1)].

•

Calculate the volume of the 21 mg/mL reconstituted Ogivri 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 Ogivri for infusion diluted in polyvinylchloride or polyethylene bags containing 0.9% Sodium Chloride Injection, USP, should be stored at 2° to 8°C (36° 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 .

3 DOSAGE FORMS AND STRENGTHS

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For injection: 150 mg of Ogivri as an off-white to pale yellow lyophilized powder in a single-dose vial.

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For injection: 420 mg of Ogivri as an off-white to pale yellow lyophilized powder in a multiple-dose vial supplied with a separate vial containing 20 mL of Bacteriostatic Water for Injection (BWFI), to be used as a diluent.

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For injection: 420 mg of Ogivri as an off-white to pale yellow lyophilized powder in a multiple-dose vial. No diluent is provided.