Table of Contents
1. NAME OF THE MEDICINAL PRODUCT

 ZYTIGA 250 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

 Each tablet contains 250 mg of abiraterone acetate.

Excipients

Each tablet contains 189 mg of lactose and 6.8 mg of sodium.

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

 Tablet.

White to off-white oval tablets, debossed with AA250 on one side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

 ZYTIGA is indicated with prednisone or prednisolone for the treatment of metastatic castration resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.

4.2 Posology and method of administration

 Posology

The recommended dose is 1,000 mg (four 250 mg tablets) as a single daily dose that must not be taken with food (see information on the method of administration). Taking the tablets with food increases systemic exposure to abiraterone (see sections 4.5 and 5.2).

ZYTIGA is to be taken with low dose prednisone or prednisolone. The recommended dose of prednisone or prednisolone is 10 mg daily.

Serum transaminases should be measured prior to starting treatment, every two weeks for the first three months of treatment and monthly thereafter. Blood pressure, serum potassium and fluid retention should be monitored monthly (see section 4.4).

In the event of a missed daily dose of either ZYTIGA, prednisone or prednisolone, treatment should be resumed the following day with the usual daily dose.

Hepatotoxicity

For patients who develop hepatotoxicity during treatment (alanine aminotransferase [ALT] increases above 5 times the upper limit of normal [ULN]), treatment should be withheld immediately (see section 4.4). Re-treatment following return of liver function tests to the patient's baseline may be given at a reduced dose of 500 mg (two tablets) once daily. For patients being re-treated, serum transaminases should be monitored at a minimum of every two weeks for three months and monthly thereafter. If hepatotoxicity recurs at the reduced dose of 500 mg daily, treatment should be discontinued.

If patients develop severe hepatotoxicity (ALT 20 times the upper limit of normal) anytime while on therapy, treatment should be discontinued and patients should not be re-treated.

Hepatic impairment

No dose adjustment is necessary for patients with pre-existing mild hepatic impairment, Child-Pugh Class A.

Moderate hepatic impairment (Child-Pugh Class B) has been shown to increase the systemic exposure to abiraterone by approximately four-fold following single oral doses of abiraterone acetate 1,000 mg (see section 5.2). There are no data on the clinical safety and efficacy of multiple doses of abiraterone acetate when administered to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). No dose adjustment can be predicted and ZYTIGA should be avoided in these patients.

Renal impairment

No dose adjustment is necessary for patients with renal impairment (see section 5.2). However, there is no clinical experience in patients with prostate cancer and severe renal impairment. Caution is advised in these patients (see section 4.4).

Paediatric population

There is no relevant use of this medicinal product in the paediatric population, as prostate cancer is not present in children an