sting 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 and adolescents.
Method of administration
ZYTIGA should be taken at least two hours after eating and no food should be eaten for at least one hour after taking the tablets. These should be swallowed whole with water.
4.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients (see section 6.1).
- Women who are or may potentially be pregnant (see section 4.6)
4.4 Special warnings and precautions for use
Hypertension, hypokalaemia and fluid retention due to mineralocorticoid excess
The phase 3 study conducted with ZYTIGA 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%. ZYTIGA should be used with caution in patients with a history of cardiovascular disease. Safety in patients with left ventricular ejection fraction < 50% or NYHA Class III or IV heart failure has not been established. Before treatment hypertension must be controlled and hypokalaemia must be corrected.
ZYTIGA may cause hypertension, hypokalaemia and fluid retention (see section 4.8) as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition (see section 5.1). Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in incidence and severity of these adverse reactions. Caution is required in treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalaemia (e.g., those on cardiac glycosides), or fluid retention (e.g., those with heart failure), severe or unstable angina pectoris, recent myocardial infarction or ventricular arrhythmia and those with severe renal impairment. Blood pressure, serum potassium and fluid retention should be monitored before treatment and at least monthly thereafter.
Hepatotoxicity
Marked increases in liver enzymes leading to treatment discontinuation or dose modification occurred in controlled clinical studies (see section 4.8). Serum transaminase levels should be measured prior to starting treatment, every two weeks for the first three months of treatment, and monthly thereafter. If clinical symptoms or signs suggestive of hepatotoxicity develop, serum transaminases, in particular serum ALT, should be measured immediately. If at any time the AL |
