Special Warning : אזהרת שימוש

5.7 Special warnings and precautions for use

Hypertension, hypokalaemia, fluid retention and cardiac failure due to mineralocorticoid excess ZYTIGA 250 MG may cause hypertension, hypokalaemia and fluid retention (see section 5.8) as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition (see section 6.1). 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).

ZYTIGA 250 MG should be used with caution in patients with a history of cardiovascular disease. The Phase 3 studies conducted with ZYTIGA 250 MG 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 (NYHA) III or IV heart failure (study 301) or Class II to IV heart failure (studies 3011 and 302) or cardiac ejection fraction measurement of < 50%. In studies 3011 and 302, patients with atrial fibrillation, or other cardiac arrhythmia requiring medical therapy were excluded. Safety in patients with left ventricular ejection fraction (LVEF) < 50% or NYHA Class III or IV heart failure (in study 301) or NYHA Class II to IV heart failure (in studies 3011 and 302) was not established (see sections 5.8 and 6.1).

Before treating patients with a significant risk for congestive heart failure (e.g.a history of cardiac failure, uncontrolled hypertension, or cardiac events such as ischaemic heart disease), consider obtaining an assessment of cardiac function (e.g. echocardiogram). Before treatment with ZYTIGA 250 MG, cardiac failure should be treated and cardiac function optimised. Hypertension, hypokalaemia and fluid retention should be corrected and controlled.
During treatment, blood pressure, serum potassium, fluid retention (weight gain, peripheral oedema), and other signs and symptoms of congestive heart failure should be monitored every 2 weeks for 3 months, then monthly thereafter and abnormalities corrected. QT prolongation has been observed in patients experiencing hypokalaemia in association with ZYTIGA 250 MG treatment. Assess cardiac function as clinically indicated, institute appropriate management and consider discontinuation of this treatment if there is a clinically significant decrease in cardiac function (see section 5.2).

Hepatotoxicity and hepatic impairment
Marked increases in liver enzymes leading to treatment discontinuation or dose modification occurred in controlled clinical studies (see section 5.8). 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 should be measured immediately. If at any time the ALT or AST rises above 5 times the ULN, treatment should be interrupted immediately and liver function closely monitored.
Re-treatment may take place only after return of liver function tests to the patient’s baseline and at a reduced dose level (see section 5.2).


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.

Patients with active or symptomatic viral hepatitis were excluded from clinical trials; thus, there are no data to support the use of ZYTIGA 250 MG in this population.

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). The use of ZYTIGA 250 MG should be cautiously assessed in patients with moderate hepatic impairment, in whom the benefit clearly should outweigh the possible risk (see sections 5.2 and 6.2). ZYTIGA 250 MG should not be used in patients with severe hepatic impairment (see sections 5.2, 5.3 and 6.2).

There have been rare post-marketing reports of acute liver failure and hepatitis fulminant, some with fatal outcome (see section 5.8).

Corticosteroid withdrawal and coverage of stress situations
Caution is advised and monitoring for adrenocortical insufficiency should occur if patients are withdrawn from prednisone If ZYTIGA 250 MG is continued after corticosteroids are withdrawn, patients should be monitored for symptoms of mineralocorticoid excess (see information above).

In patients on prednisone who are subjected to unusual stress, an increased dose of corticosteroids may be indicated before, during and after the stressful situation.

Bone density
Decreased bone density may occur in men with metastatic advanced prostate cancer. The use of ZYTIGA 250 MG in combination with a glucocorticoid could increase this effect.

Prior use of ketoconazole
Lower rates of response might be expected in patients previously treated with ketoconazole for prostate cancer.

Hyperglycaemia
The use of glucocorticoids could increase hyperglycaemia, therefore blood sugar should be measured frequently in patients with diabetes.

Hypoglycaemia
Cases of hypoglycaemia have been reported when ZYTIGA 250 MG plus prednisone was administered to patients with pre-existing diabetes receiving pioglitazone or repaglinide (see section 4.5); therefore, blood sugar should be monitored in patients with diabetes.

Use with chemotherapy
The safety and efficacy of concomitant use of ZYTIGA 250 MG with cytotoxic chemotherapy has not been established (see section 6.1).

Intolerance to excipients
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicinal product contains 27.2 mg (1.18 mmol) sodium per dose of four tablets, equivalent to 1.36% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Potential risks
Anaemia and sexual dysfunction may occur in men with metastatic prostate cancer including those undergoing treatment with ZYTIGA 250 MG.


Skeletal muscle effects
Cases of myopathy and rhabdomyolysis have been reported in patients treated with ZYTIGA 250 MG. Most cases developed within the first 6 months of treatment and recovered after ZYTIGA 250 MG withdrawal. Caution is recommended in patients concomitantly treated with medicinal products known to be associated with myopathy/rhabdomyolysis.

Interactions with other medicinal products
Strong inducers of CYP3A4 during treatment are to be avoided unless there is no therapeutic alternative, due to risk of decreased exposure to abiraterone (see section 5.5).

Combination of abiraterone and prednisone with Ra-223
Treatment with abiraterone and prednisone in combination with Ra-223 is contraindicated (see section 5.3) due to an increased risk of fractures and a trend for increased mortality among asymptomatic or mildly symptomatic prostate cancer patients as observed in clinical trials.

It is recommended that subsequent treatment with Ra-223 is not initiated for at least 5 days after the last administration of ZYTIGA 250 MG in combination with prednisone.

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