Administration:

Administer Kadcyla as an intravenous infusion only with a 0.22 micron in-line polyethersulfone (PES) filter. Do not administer as an intravenous push or bolus.
Do not mix Kadcyla, or administer as an infusion, with other medicinal products.
In order to improve traceability of biological medicinal products, the tradename of the administered product should be clearly recorded (or stated) in the patient file.
Reconstitution:

Use aseptic technique for reconstitution and preparation of dosing solution. Appropriate procedures for the preparation of chemotherapeutic drugs should be used.
Using a sterile syringe, slowly inject 5 mL of Sterile Water for Injection into the 100 mg Kadcyla vial, or 8 mL of Sterile Water for Injection into the 160 mg Kadcyla vial to yield a solution containing 20 mg/mL. Swirl the vial gently until completely dissolved. Do not shake. Inspect the reconstituted solution for particulates and discoloration.
The reconstituted solution should be clear to slightly opalescent and free of visible particulates. The color of the reconstituted solution should be colorless to pale brown. Do not use if the reconstituted solution contains visible particulates or is cloudy or discolored.
The reconstituted lyophilized vials should be used immediately following reconstitution with Sterile Water for Injection. If not used immediately, the reconstituted Kadcyla vials can be stored for up to 24 hours in a refrigerator at 2ºC to 8ºC (36°F to 46°F); discard unused Kadcyla after 24 hours. Do not freeze.
The reconstituted product contains no preservative and is intended for single-use only.
Dilution:

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

Calculate the volume of the 20 mg/mL reconstituted Kadcyla solution needed.
Withdraw this amount from the vial and add it to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection. Do not use Dextrose (5%) solution.
Gently invert the bag to mix the solution in order to avoid foaming.
The diluted Kadcyla infusion solution should be used immediately. If not used immediately, the solution may be stored in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours prior to use. This storage time is additional to the time allowed for the recon
Table 1 Recommended Dose Reduction Schedule for Adverse Events

Dose Reduction Schedule
Dose Level
Starting dose 3.6 mg/kg
First dose reduction 3 mg/kg
Second dose reduction 2.4 mg/kg
Requirement for further dose reduction Discontinue treatment

Hepatotoxicity [see Warnings and Precautions (5.1)]

A reduction in the dose of Kadcyla is recommended in the case of hepatotoxicity exhibited as increases in serum transaminases and/or hyperbilirubinemia (see Tables 2 and 3).

Table 2 Dose Modification Guidelines for Increased Serum Transaminases (AST/ALT) Grade 2
(> 2.5 to ≤ 5 × ULN) Grade 3
(> 5 to ≤ 20 × ULN) Grade 4
(> 20 × ULN)
ALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal.
Treat at same dose level. Do not administer Kadcyla until AST/ALT recovers to Grade ≤ 2, and then reduce one dose level. Permanently discontinue Kadcyla.
Table 3 Dose Modification Guidelines for Hyperbilirubinemia Grade 2
(> 1.5 to ≤ 3 × ULN) Grade 3
(> 3 to ≤ 10 × ULN) Grade 4
(> 10 &