Kadcyla 100 mg powder for concentrate for solution for infusion.
Kadcyla 160 mg powder for concentrate for solution for infusion.
100 mg single-use vial containing powder for concentrate for infusion solution delivers 5 mL of 20 mg/mL of trastuzumab emtansine after reconstitution (see section 6.6).
160 mg single-use vial containing powder for concentrate for infusion solution delivers 8 mL of 20 mg/mL of trastuzumab emtansine after reconstitution (see section 6.6).
Trastuzumab emtansine is an antibody-drug conjugate that contains trastuzumab, a humanised IgG1 monoclonal antibody produced by mammalian (Chinese hamster ovary) cell suspension culture, covalently linked to DM1, a microtubule inhibitor, via the stable thioether linker MCC (4-[N-maleimidomethyl] cyclohexane-1-carboxylate).
For the full list of excipients, see section 6.1.
Powder for concentrate for solution for infusion.
White to off-white lyophilised powder.
Kadcyla, as a single agent, is indicated for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:
• Received prior therapy for locally advanced or metastatic disease, or
• Developed disease recurrence during or within six months of completing adjuvant therapy.
Kadcyla should only be prescribed by a physician and administered under the supervision of a healthcare professional who is experienced in the treatment of cancer patients.
Patients treated with trastuzumab emtansine should have HER2 positive tumour status, defined as a score of 3 + by immunohistochemistry (IHC) or a ratio of ≥ 2.0 by in situ hybridization (ISH) assessed by a CE-marked In Vitro Diagnostic (IVD) medical device. If a CE-marked IVD is not available, the HER2-status should be assessed by an alternate validated test.
In order to prevent medication errors it is important to check the vial labels to ensure that the medicinal product being prepared and administered is Kadcyla (trastuzumab emtansine) and not Herceptin (trastuzumab).
Posology
The recommended dose of trastuzumab emtansine is 3.6 mg/kg bodyweight administered as an intravenous infusion every 3 weeks (21-day cycle). Patients should be treated until disease progression or unacceptable toxicity.
The initial dose should be administered as a 90 minute intravenous infusion. Patients should be observed during the infusion and for at least 90 minutes following the initial infusion for fever, chills, or other infusion-related reactions. The infusion site should be closely monitored for possible subcutaneous infiltration during administration (see section 4.8).
If the prior infusion was well tolerated, subsequent doses of trastuzumab emtansine may be administered as 30 minute infusions. Patients should be observed during the infusion and for at least 30 minutes after infusion.
The infusion rate of trastuzumab emtansine should be slowed or interrupted if the patient develops infusion-related symptoms (see sections 4.4 and 4.8). Trastuzumab emtansine should be discontinued in case of life-threatening infusion reactions.
Medicinal products to treat allergic/anaphylactic infusion reactions, as well as emergency equipment should be available for immediate use (see section 4.4).
Delayed or missed dose
If a planned dose is 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 next dose should be administered in accordance with the dosing recommendations (see section 4.2, Posology).
Dose modification
Management of symptomatic adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of Kadcyla as per guidelines provided in text and Tables 1 to 5.
Kadcyla dose should not be re-escalated after a dose reduction is made.
Table 1 Dose reduction schedule
|
Dose reduction schedule
(Starting dose is 3.6 mg/kg)
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Dose to be administered
|
|
First dose reduction
|
3 mg/kg
|
|
Second dose reduction
|
2.4 mg/kg
|
|
Requirement for further dose reduction
|
Discontinue treatment
|
Table 2 Dose modification guidelines for increased transaminases (AST/ALT)
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Grade 2
(> 2.5 to ≤ 5 × the ULN)
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Grade 3
(> 5 to ≤ 20 × the ULN)
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Grade 4
(> 20 × the ULN)
|
|
No dose modification is required.
|
Do not administer trastuzumab emtansine until AST/ALT recovers to Grade ≤ 2 (>2.5 to ≤5 x ULN), and then dose reduce (see table 1).
|
Discontinue trastuzumab emtansine.
|
ALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal.
Table 3 Dose modification guidelines for hyperbilirubinemia
|
Grade 2
(> 1.5 to ≤ 3 × the ULN)
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Grade 3
(> 3 to ≤ 10 × the ULN)
|
Grade 4
(> 10 × the ULN)
|
|
Do not administer trastuzumab emtansine until total bilirubin recovers to Grade ≤ 1 (>ULN to 1.5x ULN). No dose modification is required.
|
Do not administer trastuzumab emtansine until total bilirubin recovers to Grade ≤ 1 (>ULN to 1.5x ULN), and then dose reduce (see table 1).
|
Discontinue trastuzumab emtansine.
|
ULN = upper limit of normal.
Table 4 Dose modification guidelines for thrombocytopenia
