eatening 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 Hyperbilirubinemia
Grade 2
(> 1.5 to ≤ 3 × ULN)
Grade 3
(> 3 to ≤ 10 × ULN)
Grade 4
(> 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)]
Table 4 Dose Modifications for Left Ventricular Dysfunction
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 (5.6)]
A reduction in dose is recommended in the case of Grade 4 thrombocytopenia (platelets < 25,000/mm3) (see Table 5).
Table 5 Dose Modification Guidelines for Thrombocytopenia
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/m
