Generic name: ADO-TRASTUZUMAB EMTANSINE 20mg in 1mL
Dosage form: injection, powder, lyophilized, for solution
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Recommended Doses and Schedules
The recommended dose of KADCYLA is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. Do not administer KADCYLA at doses greater than 3.6 mg/kg. Do not substitute KADCYLA for or with trastuzumab.
Closely monitor the infusion site for possible subcutaneous infiltration during drug administration [see Warnings and Precautions (5.10)].
First infusion: Administer infusion over 90 minutes. Patients should be observed during the infusion and for at least 90 minutes following the initial dose for fever, chills, or other infusion-related reactions [see Warnings and Precautions (5.5)].
Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated. Patients should be observed during the infusion and for at least 30 minutes after infusion.
KADCYLA dose should not be re-escalated after a dose reduction is made.
If a planned dose is delayed or missed, it should be administered as soon as possible; do not wait until the next planned cycle. The schedule of administration should be adjusted to maintain a 3-week interval between doses. The infusion may be administered at the dose and rate the patient tolerated in the most recent infusion.
The infusion rate of KADCYLA should be slowed or interrupted if the patient develops an infusion-related reaction. Permanently discontinue KADCYLA for life-threatening infusion-related reactions [see Warnings and Precautions (5.5)].
Management of increased serum transaminases, hyperbilirubinemia, left ventricular dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy may require temporary interruption, dose reduction or treatment discontinuation of KADCYLA as per guidelines provided in Tables 1 to 5.
|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)]
(> 2.5 to ≤ 5 × ULN)
(> 5 to ≤ 20 × ULN)
(> 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.|
(> 1.5 to ≤ 3 × ULN)
(> 3 to ≤ 10 × ULN)
(> 10 × ULN)
|Do not administer KADCYLA until total bilirubin recovers to Grade ≤ 1, and then treat at same dose level.||Do not administer KADCYLA until total bilirubin recovers to Grade ≤ 1, and then reduce one dose level.||Permanently discontinue KADCYLA.|
Permanently discontinue KADCYLA treatment in patients with serum transaminases > 3 × ULN and concomitant total bilirubin > 2 × ULN.
Permanently discontinue KADCYLA in patients diagnosed with nodular regenerative hyperplasia (NRH).
Left Ventricular Dysfunction [see Warnings and Precautions (5.2)]
|Symptomatic CHF||LVEF < 40%||LVEF 40% to ≤ 45% and decrease is ≥ 10% points from baseline||LVEF 40% to ≤ 45% and decrease is < 10% points from baseline||LVEF > 45%|
|CHF = Congestive Heart Failure; LVEF = Left Ventricular Ejection Fraction|
|Discontinue KADCYLA||Do not administer KADCYLA.||Do not administer KADCYLA.||Continue treatment with KADCYLA.||Continue treatment with KADCYLA.|
|Repeat LVEF assessment within 3 weeks. If LVEF < 40% is confirmed, discontinue KADCYLA.||Repeat LVEF assessment within 3 weeks. If the LVEF has not recovered to within 10% points from baseline, discontinue KADCYLA.||Repeat LVEF assessment within 3 weeks.|
Thrombocytopenia [see Warnings and Precautions (5.7)]
A reduction in dose is recommended in the case of Grade 4 thrombocytopenia (platelets < 25,000/mm3) (see Table 5).
|Grade 3||Grade 4|
|PLT 25,000/mm3 to < 50,000/mm3||PLT < 25,000/mm3|
|PLT = Platelets|
|Do not administer KADCYLA until platelet count recovers to ≤ Grade 1 (≥ 75,000/mm3), and then treat at same dose level.||Do not administer KADCYLA until platelet count recovers to ≤ Grade 1 (≥ 75,000/mm3), and then reduce one dose level.|
Pulmonary Toxicity [see Warnings and Precautions (5.4)]
KADCYLA should be permanently discontinued in patients diagnosed with interstitial lung disease (ILD) or pneumonitis.
Peripheral Neuropathy [see Warnings and Precautions (5.8)]
KADCYLA should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to ≤ Grade 2.
Preparation for Administration
In order to prevent medication errors it is important to check the vial labels to ensure that the drug being prepared and administered is KADCYLA (ado-trastuzumab emtansine) and not trastuzumab.
- Administer KADCYLA as an intravenous infusion only with a 0.2 or 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.
- 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.
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 reconstituted vials. Do not freeze or shake.