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.

Recommended Doses and Schedules

• Do not administer as an intravenous push or bolus. Do not mix Ontruzant with other drugs.
• Do not substitute Ontruzant (trastuzumab-dttb) for or with ado-trastuzumab emtansine.

Important Dosing Considerations

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

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

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 Ontruzant (trastuzumab-dttb) and not ado-trastuzumab emtansine.

​420 mg Multiple-dose vial

​Reconstitution: Reconstitute each 420 mg vial of Ontruzant 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-dttb that delivers 20 mL (420 mg trastuzumab-dttb). 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 powder of Ontruzant, 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-dttb.
• ​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 Ontruzant in the refrigerator at 2° to 8°C (36° to 46°F); discard unused Ontruzant after 28 days. If Ontruzant is reconstituted with SWFI without preservative, use immediately and discard any unused portion. Do not freeze.

​Dilution:

• ​Determine the dose (mg) of Ontruzant [see Dosage and Administration (2.2)]. Calculate the volume of the 21 mg/mL reconstituted Ontruzant 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 Ontruzant 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.