of these risks and the need for effective contraception. (5.3, 8.1, 8.6)
1 INDICATIONS AND USAGE
KADCYLA™, as a single agent, is indicated for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:
•Received prior therapy for metastatic disease, or
•Developed disease recurrence during or within six months of completing adjuvant therapy.
2 DOSAGE AND ADMINISTRATION
2.1 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 (5.9)].
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.
2.2 Dose Modifications
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.
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 Hyperbilirubin
