Cardiomyopathy

[see Boxed Warning, 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 ( > 8weeks) LVEF decline or for suspension of Herceptin dosing on more than 3 occasions for cardiomyopathy.
2.3 Preparation for Administration

Reconstitution

Reconstitute each 440mg vial of Herceptin with 20mL of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative to yield a multi‑dose solution containing 21mg/mL trastuzumab. In patients with known hypersensitivity to benzyl alcohol, reconstitute with 20mL 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 20mL 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 5minutes.
• 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 28days. 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 21mg/mL reconstituted Herceptin solution needed, withdraw this amount from the vial and add it to an infusion bag containing 250mL 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

440mg lyophilized powder per multi‑use vial.
4 CONTRAINDICATIONS

None.
5 WARNINGS AND PRECAUTIONS
5.1 Cardiomyopathy

Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy]. Herceptin can also cause asymptomatic decline in left ventricular ejection fraction (LVEF).

There is a 4–6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Herceptin as a single agent or in combination therapy compared with those not recei