Pregnancy

ZYTIGA is not for use in women. Abiraterone acetate is contraindicated in women who are or may potentially be pregnant (see section 4.3 and 5.3).

Breast-feeding

ZYTIGA is not for use in women. It is not known if either abiraterone acetate or its metabolites are excreted in human milk.

Fertility

Reproductive toxicology studies were not conducted with abiraterone acetate. No fertility data are available.

4.7 Effects on ability to drive and use machines

 ZYTIGA has no or negligible influence on the ability to drive or use machines.

4.8 Undesirable effects

 Summary of the safety profile

The most common adverse reactions seen are peripheral oedema, hypokalaemia, hypertension and urinary tract infection.

ZYTIGA may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic consequence of its mechanism of action. In a phase 3 study, anticipated mineralocorticoid adverse reactions were seen more commonly in patients treated with ZYTIGA than in patients treated with placebo: hypokalaemia 17% versus 8%, hypertension 9% versus 7% and fluid retention (peripheral oedema) 25% versus 17%, respectively. In patients treated with ZYTIGA, CTCAE (version 3.0) Grades 3 and 4 hypokalaemia and CTCAE (version 3.0) Grades 3 and 4 hypertension were observed in 4% and 1% of patients, respectively. Mineralocorticoid reactions generally were able to be successfully managed medically. Concomitant use of a corticosteroid reduces the incidence and severity of these adverse reactions (see section 4.4).

Tabulated summary of adverse reactions

In studies of patients with metastatic advanced prostate cancer who were using a luteinising hormone-releasing hormone (LHRH) agonist, or were previously treated with orchiectomy, ZYTIGA was administered at a dose of 1,000 mg daily in combination with low dose prednisone or prednisolone (10 mg daily). Patients were intolerant to or had failed up to two prior chemotherapy regimens, one of which contained a taxane.

Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 1: Adverse reactions identified in clinical studies
 
Infections and infestations
 very common: urinary tract infection
 
Endocrine disorders
 uncommon: adrenal insufficiency
 
Metabolism and nutrition disorders
 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 w