sp;very common: hypokalaemia
common: hypertriglyceridaemia
Cardiac disorders
common: cardiac failure*, angina pectoris, arrhythmia, atrial fibrillation, tachycardia
Vascular disorders
very common: hypertension
Hepatobiliary disorders
common: alanine aminotransferase increased
General disorders and administration site conditions
very common: oedema peripheral
* Cardiac failure also includes congestive heart failure, left ventricular dysfunction and ejection fraction decreased
The following CTCAE (version 3.0) Grade 3 adverse reactions occurred in patients treated with ZYTIGA: hypokalaemia 3%; urinary tract infection 2%; peripheral oedema, alanine aminotransferase increased, hypertension, cardiac failure and atrial fibrillation, 1% each. CTCAE (version 3.0) Grade 3 hypertriglyceridaemia and angina pectoris occurred in < 1% of patients. CTCAE (version 3.0) Grade 4 peripheral oedema, hypokalaemia, urinary tract infection, and cardiac failure occurred in < 1% of patients.
Description of selected adverse reactions
Cardiovascular reactions
The phase 3 study excluded patients with uncontrolled hypertension, clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class III or IV heart disease or cardiac ejection fraction measurement of < 50%. All patients enrolled (both active and placebo-treated patients) were concomitantly treated with androgen deprivation therapy, predominantly with the use of LHRH agonists, which has been associated with diabetes, myocardial infarction, cerebrovascular accident and sudden cardiac death. Cardiovascular adverse reactions in the phase 3 study occurred in 11% of patients who received ZYTIGA and in 7% of patients who received placebo.
Hepatotoxicity
Hepatotoxicity with elevated ALT, aspartate transaminase (AST) and total bilirubin has been reported in patients treated with ZYTIGA. Across all clinical studies, liver function test elevations (ALT or AST increases of > 5 x ULN or bilirubin increases > 1.5 x ULN) were reported in approximately 2% of patients who received ZYTIGA, typically during the first 3 months after starting treatment. In the phase 3 clinical study, patients whose baseline ALT or AST were elevated were more likely to experience liver function test elevations than those beginning with normal values. When elevations of either ALT or AST > 5 x ULN, or elevations in bilirubin > 3 x ULN were observed, ZYTIGA was withheld or discontinued. In two instances marked increases in liver function tests occurred (see section 4.4). These two patients with normal baseline hepatic function, experienced ALT or AST elevations 15 to 40 x ULN and bilirubin elevations 2 to 6 x ULN. Upon discontinuation of ZYTIGA, both patients had normalisation of their liver function tests and one patient was re-treated without recurrence of the elevations.
In clinical trials, the risk for hepatotoxicity was mitigated by exclusion of patients with active or symptomatic hepatitis or baseline ALT and AST 2.5 x ULN in the absence of liver metastases and > 5 x ULN if liver metastases were present. Abnormal liver function tests developing in patients participating in clinical trials were vigorously managed by requiring treatment interruption and permitting re-treatment only after return of liver function tests to the pat |
