13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Metastatic Breast Cancer

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied/Storage

16.2 Special Handling

17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION

Do Not Substitute KADCYLA for or with Trastuzumab

WARNING: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY
•Hepatotoxicity: Serious hepatotoxicity has been reported, including liver failure and death in patients treated with KADCYLA. Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases or total bilirubin. (2.2, 5.1)
 •Cardiac Toxicity: KADCYLA administration may lead to reductions in left ventricular ejection fraction (LVEF). eva luate left ventricular function in all patients prior to and during treatment with KADCYLA. Withhold treatment for clinically significant decrease in left ventricular function. (2.2, 5.2)
 •Embryo-Fetal Toxicity: Exposure to KADCYLA can result in embryo-fetal death or birth defects. Advise patients 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-thr