ZYTIGA Tablet Ref.[28092] Active ingredients: Abiraterone

This medicinal product should be prescribed by an appropriate healthcare professional.

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 “Method of administration” below). Taking the tablets with food increases systemic exposure to abiraterone (see sections 4.5 and 5.2).

Dosage of prednisone or prednisolone

For mHSPC, ZYTIGA is used with 5 mg prednisone or prednisolone daily.

For mCRPC, ZYTIGA is used with 10 mg prednisone or prednisolone daily.

Medical castration with luteinising hormone releasing hormone (LHRH) analogue should be continued during treatment in patients not surgically castrated.

Recommended monitoring

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. However, patients with a significant risk for congestive heart failure hould be monitored every 2 weeks for the first three months of treatment and monthly thereafter (see section 4.4).

In patients with pre-existing hypokalaemia or those that develop hypokalaemia whilst being treated with ZYTIGA, consider maintaining the patient’s potassium level at ≥4.0 mM. For patients who develop Grade ≥ 3 toxicities including hypertension, hypokalaemia, oedema and other non-mineralocorticoid toxicities, treatment should be withheld and appropriate medical management should be instituted. Treatment with ZYTIGA should not be reinitiated until symptoms of the toxicity have resolved to Grade 1 or baseline. 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 or aspartate aminotransferase [AST] 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 or AST 20 times the ULN) 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. The use of ZYTIGA should be cautiously assessed in patients with moderate hepatic impairment, in whom the benefit clearly should outweigh the possible risk (see sections 4.2 and 5.2). ZYTIGA should not be used in patients with severe hepatic impairment (see sections 4.3, 4.4 and 5.2).

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 ZYTIGA in the paediatric population.

Method of administration

ZYTIGA is for oral use.

The tablets should be taken at least one hour before or at least two hours after eating. These should be swallowed whole with water.

Human experience of overdose with ZYTIGA is limited.

There is no specific antidote. In the event of an overdose, administration should be withheld and general supportive measures undertaken, including monitoring for arrhythmias, hypokalaemia and for signs and symptoms of fluid retention. Liver function also should be assessed.

2 years.

This medicinal product does not require special storage conditions.

Round white HDPE bottles fitted with a polypropylene child-resistant closure containing 120 tablets.

Each pack contains one bottle.

Based on its mechanism of action, this medicinal product may harm a developing foetus; therefore, women who are pregnant or may be pregnant should not handle it without protection, e.g., gloves.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements. This medicinal product may pose a risk to the aquatic environment (see section 5.3).