Zytiga

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

ZYTIGA 250 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 250 mg of abiraterone acetate.

Excipients with known effect
Each tablet contains 189 mg of lactose and 6.8 mg of sodium.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet
White to off-white oval tablets (15.9 mm long x 9.5 mm wide), debossed with AA250 on one side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

ZYTIGA is indicated with prednisone or prednisolone for:
 the treatment of newly diagnosed high risk metastatic hormone sensitive prostate cancer 

(mHSPC) in adult men in combination with androgen deprivation therapy (ADT) (see section 
5.1)

 the treatment of metastatic castration resistant prostate cancer (mCRPC) in adult men who are 
asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom 
chemotherapy is not yet clinically indicated (see section 5.1)

 the treatment of mCRPC in adult men whose disease has progressed on or after a 
docetaxel-based chemotherapy regimen.

4.2 Posology and method of administration

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 



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should 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.

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
- Women who are or may potentially be pregnant (see section 4.6).
- Severe hepatic impairment [Child-Pugh Class C (see sections 4.2, 4.4 and 5.2)].
- ZYTIGA with prednisone or prednisolone is contraindicated in combination with Ra-223.



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4.4 Special warnings and precautions for use

Hypertension, hypokalaemia, fluid retention and cardiac failure due to mineralocorticoid excess
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).

ZYTIGA should be used with caution in patients with a history of cardiovascular disease. The Phase 3 
studies 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 (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 4.8 and 5.1).

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, 
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 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 4.2).

Hepatotoxicity and hepatic impairment
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 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 4.2).

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 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 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 4.2, 4.3 and 5.2).

There have been rare post-marketing reports of acute liver failure and hepatitis fulminant, some with 
fatal outcome (see section 4.8).



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

In patients on prednisone or prednisolone 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 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 plus prednisone/prednisolone 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 with cytotoxic chemotherapy has not been 
established (see section 5.1).

Intolerance to excipients
This medicinal product contains lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicine. This medicinal product also contains more than 1 mmol (or 27.2 mg) sodium per dose of 
four tablets. To be taken into consideration by patients on a controlled sodium diet.

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

Skeletal muscle effects
Cases of myopathy and rhabdomyolysis have been reported in patients treated with ZYTIGA. Most 
cases developed within the first 6 months of treatment and recovered after ZYTIGA 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 4.5).

Combination of abiraterone and prednisone/prednisolone with Ra-223
Treatment with abiraterone and prednisone/prednisolone in combination with Ra-223 is 
contraindicated (see section 4.3) 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.



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

4.5 Interaction with other medicinal products and other forms of interaction

Effect of food on abiraterone acetate
Administration with food significantly increases the absorption of abiraterone acetate. The efficacy 
and safety when given with food have not been established therefore this medicinal product must not 
be taken with food (see sections 4.2 and 5.2).

Interactions with other medicinal products
Potential for other medicinal products to affect abiraterone exposures
In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 
inducer rifampicin, 600 mg daily for 6 days followed by a single dose of abiraterone acetate 1,000 mg, 
the mean plasma AUC∞ of abiraterone was decreased by 55%.

Strong inducers of CYP3A4 (e.g., phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, 
phenobarbital, St John's wort [Hypericum perforatum]) during treatment are to be avoided, unless 
there is no therapeutic alternative.

In a separate clinical pharmacokinetic interaction study of healthy subjects, co-administration of 
ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the 
pharmacokinetics of abiraterone.

Potential to affect exposures to other medicinal products
Abiraterone is an inhibitor of the hepatic drug-metabolising enzymes CYP2D6 and CYP2C8.
In a study to determine the effects of abiraterone acetate (plus prednisone) on a single dose of the 
CYP2D6 substrate dextromethorphan, the systemic exposure (AUC) of dextromethorphan was 
increased approximately 2.9 fold. The AUC24 for dextrorphan, the active metabolite of 
dextromethorphan, increased approximately 33%.

Caution is advised when administering with medicinal products activated by or metabolised by 
CYP2D6, particularly with medicinal products that have a narrow therapeutic index. Dose reduction of 
medicinal products with a narrow therapeutic index that are metabolised by CYP2D6 should be 
considered. Examples of medicinal products metabolised by CYP2D6 include metoprolol, 
propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecainide, codeine, 
oxycodone and tramadol (the latter three medicinal products requiring CYP2D6 to form their active 
analgesic metabolites).

In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone was increased by 
46% and the AUCs for M-III and M-IV, the active metabolites of pioglitazone, each decreased by 10% 
when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Patients 
should be monitored for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic 
index if used concomitantly. Examples of medicinal products metabolised by CYP2C8 include 
pioglitazone and repaglinide (see section 4.4).

In vitro, the major metabolites abiraterone sulphate and N-oxide abiraterone sulphate were shown to 
inhibit the hepatic uptake transporter OATP1B1 and as a consequence it may increase the 
concentrations of medicinal products eliminated by OATP1B1. There are no clinical data available to 
confirm transporter based interaction.

Use with products known to prolong QT interval
Since androgen deprivation treatment may prolong the QT interval, caution is advised when 
administering ZYTIGA with medicinal products known to prolong the QT interval or medicinal 
products able to induce torsades de pointes such as class IA (e.g. quinidine, disopyramide) or class III 
(e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, 
moxifloxacin, antipsychotics, etc.



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Use with Spironolactone
Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels. 
Use with ZYTIGA is not recommended (see section 5.1).

4.6 Fertility, pregnancy and lactation

Women of childbearing potential
There are no human data on the use of ZYTIGA in pregnancy and this medicinal product is not for use 
in women of childbearing potential.

Contraception in males and females
It is not known whether abiraterone or its metabolites are present in semen. A condom is required if 
the patient is engaged in sexual activity with a pregnant woman. If the patient is engaged in sex with a 
woman of childbearing potential, a condom is required along with another effective contraceptive 
method. Studies in animals have shown reproductive toxicity (see section 5.3).

Pregnancy
ZYTIGA is not for use in women and 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.

Fertility
Abiraterone affected fertility in male and female rats, but these effects were fully reversible (see 
section 5.3).

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

Summary of the safety profile
In an analysis of adverse reactions of composite Phase 3 studies with ZYTIGA, adverse reactions that 
were observed in ≥10% of patients were peripheral oedema, hypokalaemia, hypertension, urinary tract 
infection, and alanine aminotransferase increased and/or aspartate aminotransferase increased.
Other important adverse reactions include, cardiac disorders, hepatotoxicity, fractures, and allergic 
alveolitis.

ZYTIGA may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic 
consequence of its mechanism of action. In Phase 3 studies, anticipated mineralocorticoid adverse 
reactions were seen more commonly in patients treated with abiraterone acetate than in patients treated 
with placebo: hypokalaemia 18% vs. 8%, hypertension 22% vs. 16% and fluid retention (peripheral 
oedema) 23% vs. 17%, respectively. In patients treated with abiraterone acetate versus patients treated 
with placebo: CTCAE (version 4.0) Grades 3 and 4 hypokalaemia were observed in 6% versus 1%, 
CTCAE (version 4.0) Grades 3 and 4 hypertension were observed in 7% versus 5%, and fluid 
retention (peripheral oedema) Grades 3 and 4 were observed in 1% versus 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 list of adverse reactions
In studies of patients with metastatic advanced prostate cancer who were using an LHRH analogue, or 
were previously treated with orchiectomy, ZYTIGA was administered at a dose of 1,000 mg daily in 



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combination with low dose prednisone or prednisolone (either 5 or 10 mg daily depending on the 
indication).

Adverse reactions observed during clinical studies and post-marketing experience 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) and not known (frequency cannot be estimated from the available data).

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

Table 1: Adverse reactions identified in clinical studies and post-marketing
System Organ Class Adverse reaction and frequency
Infections and infestations very common: urinary tract infection

common: sepsis
Immune system disorders not known: anaphylactic reactions
Endocrine disorders uncommon: adrenal insufficiency
Metabolism and nutrition disorders very common: hypokalaemia

common: hypertriglyceridaemia
Cardiac disorders common: cardiac failure*, angina pectoris, 

atrial fibrillation, tachycardia
uncommon: other arrhythmias
not known: myocardial infarction,
QT prolongation (see sections 4.4 and 4.5)

Vascular disorders very common: hypertension
Respiratory, thoracic and mediastinal 
disorders

rare: allergic alveolitisa

Gastrointestinal disorders very common: diarrhoea
common: dyspepsia

Hepatobiliary disorders very common: alanine aminotransferase 
increased and/or aspartate aminotransferase 
increased b

rare: hepatitis fulminant, acute hepatic failure
Skin and subcutaneous tissue disorders common: rash
Musculoskeletal and connective tissue 
disorders

uncommon: myopathy, rhabdomyolysis

Renal and urinary disorders common: haematuria
General disorders and administration site 
conditions

very common: oedema peripheral

Injury, poisoning and procedural 
complications

common: fractures**

* Cardiac failure also includes congestive heart failure, left ventricular dysfunction and ejection fraction decreased
** Fractures includes osteoporosis and all fractures with the exception of pathological fractures
a Spontaneous reports from post-marketing experience
b Alanine aminotransferase increased and/or aspartate aminotransferase increased includes ALT increased, AST 

increased, and hepatic function abnormal.

The following CTCAE (version 4.0) Grade 3 adverse reactions occurred in patients treated with 
abiraterone acetate: hypokalaemia 5%; urinary tract infection 2%; alanine aminotransferase increased
and/or aspartate aminotransferase increased 4%; hypertension 6%; fractures 2%; peripheral oedema, 
cardiac failure, and atrial fibrillation 1% each. CTCAE (version 4.0) Grade 3 hypertriglyceridaemia 
and angina pectoris occurred in < 1% of patients. CTCAE (version 4.0) Grade 4 urinary tract infection, 
alanine aminotransferase increased and/or aspartate aminotransferase increased, hypokalemia, cardiac 
failure, atrial fibrillation, and fractures occurred in < 1% of patients.

A higher incidence of hypertension and hypokalemia was observed in the hormone sensitive 
population (study 3011). Hypertension was reported in 36.7% of patients in the hormone sensitive 
population (study 3011) compared to 11.8% and 20.2% in studies 301 and 302, respectively. 



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Hypokalemia was observed in 20.4% of patients in the hormone sensitive population (study 3011) 
compared to 19.2% and 14.9% in 301 and 302, respectively). 

The incidence and severity of adverse events was higher in the subgroup of patients with baseline 
ECOG2 performance status grade and also in elderly patients (≥75 years).

Description of selected adverse reactions
Cardiovascular reactions
The three Phase 3 studies 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 NYHA Class 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%. All patients enrolled 
(both active and placebo-treated patients) were concomitantly treated with androgen deprivation 
therapy, predominantly with the use of LHRH analogues, which has been associated with diabetes, 
myocardial infarction, cerebrovascular accident and sudden cardiac death. The incidence of 
cardiovascular adverse reactions in the Phase 3 studies in patients taking abiraterone acetate versus 
patients taking placebo were as follows: atrial fibrillation 2.6% vs. 2.0%, tachycardia 1.9% vs. 1.0%, 
angina pectoris 1.7% vs. 0.8%, cardiac failure 0.7% vs. 0.2%, and arrhythmia 0.7% vs. 0.5%.

Hepatotoxicity
Hepatotoxicity with elevated ALT, AST and total bilirubin has been reported in patients treated with 
abiraterone acetate. Across Phase 3 clinical studies, hepatotoxicity grades 3 and 4 (e.g., ALT or AST 
increases of > 5 x ULN or bilirubin increases > 1.5 x ULN) were reported in approximately 6% of 
patients who received abiraterone acetate, typically during the first 3 months after starting treatment. 
In Study 3011, grade 3 or 4 hepatotoxicity was observed in 8.4% of patients treated with ZYTIGA.
Ten patients who received ZYTIGA were discontinued because of hepatotoxicity; two had Grade 2 
hepatotoxicity, six had Grade 3 hepatotoxicity, and two had Grade 4 hepatotoxicity. No patient died of 
hepatotoxicity in Study 3011. In the Phase 3 clinical studies, patients whose baseline ALT or AST 
were elevated were more likely to experience liver function test elevations than those beginning with 
normal values. When elevations of either ALT or AST > 5 x ULN, or elevations in bilirubin 
> 3 x ULN were observed, abiraterone acetate was withheld or discontinued. In two instances marked 
increases in liver function tests occurred (see section 4.4). These two patients with normal baseline 
hepatic function, experienced ALT or AST elevations 15 to 40 x ULN and bilirubin elevations 2 to 
6 x ULN. Upon discontinuation of treatment, both patients had normalisation of their liver function 
tests and one patient was re-treated without recurrence of the elevations. In study 302, Grade 3 or 4 
ALT or AST elevations were observed in 35 (6.5%) patients treated with abiraterone acetate. 
Aminotransferase elevations resolved in all but 3 patients (2 with new multiple liver metastases and 1 
with AST elevation approximately 3 weeks after the last dose of abiraterone acetate). In Phase 3 
clinical studies, treatment discontinuations due to ALT and AST increases or abnormal hepatic 
function were reported in 1.1% of patients treated with abiraterone acetate and 0.6% of patients treated 
with placebo; no deaths were reported due to hepatotoxicity events.

In clinical trials, the risk for hepatotoxicity was mitigated by exclusion of patients with baseline 
hepatitis or significant abnormalities of liver function tests. In the 3011 trial, patients with baseline 
ALT and AST > 2.5 X ULN, bilirubin > 1.5 X ULN or those with active or symptomatic viral 
hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction were
excluded. In the 301 trial, patients with baseline ALT and AST ≥ 2.5 x ULN in the absence of liver 
metastases and > 5 x ULN in the presence of liver metastases were excluded. In the 302 trial, patients 
with liver metastases were not eligible and patients with baseline ALT and AST ≥ 2.5 x ULN were 
excluded. Abnormal liver function tests developing in patients participating in clinical trials were 
vigorously managed by requiring treatment interruption and permitting re-treatment only after return 
of liver function tests to the patient’s baseline (see section 4.2). Patients with elevations of ALT or 
AST > 20 x ULN were not re-treated. The safety of re-treatment in such patients is unknown. The 
mechanism for hepatotoxicity is not understood.



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Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

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.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: endocrine therapy, other hormone antagonists and related agents, ATC 
code: L02BX03

Mechanism of action
Abiraterone acetate (ZYTIGA) is converted in vivo to abiraterone, an androgen biosynthesis inhibitor. 
Specifically, abiraterone selectively inhibits the enzyme 17α-hydroxylase/C17,20-lyase (CYP17). This 
enzyme is expressed in and is required for androgen biosynthesis in testicular, adrenal and prostatic 
tumour tissues. CYP17 catalyses the conversion of pregnenolone and progesterone into testosterone 
precursors, DHEA and androstenedione, respectively, by 17α-hydroxylation and cleavage of the 
C17,20 bond. CYP17 inhibition also results in increased mineralocorticoid production by the adrenals 
(see section 4.4).

Androgen-sensitive prostatic carcinoma responds to treatment that decreases androgen levels. 
Androgen deprivation therapies, such as treatment with LHRH analogues or orchiectomy, decrease 
androgen production in the testes but do not affect androgen production by the adrenals or in the 
tumour. Treatment with ZYTIGA decreases serum testosterone to undetectable levels (using 
commercial assays) when given with LHRH analogues (or orchiectomy).

Pharmacodynamic effects
ZYTIGA decreases serum testosterone and other androgens to levels lower than those achieved by the 
use of LHRH analogues alone or by orchiectomy. This results from the selective inhibition of the 
CYP17 enzyme required for androgen biosynthesis. PSA serves as a biomarker in patients with 
prostate cancer. In a Phase 3 clinical study of patients who failed prior chemotherapy with taxanes, 
38% of patients treated with abiraterone acetate, versus 10% of patients treated with placebo, had at 
least a 50% decline from baseline in PSA levels.

Clinical efficacy and safety
Efficacy was established in three randomised placebo-controlled multicentre Phase 3 clinical studies
(studies 3011, 302 and 301) of patients with mHSPC and mCRPC. Study 3011 enrolled patients who 
were newly diagnosed (within 3 months of randomization) mHSPC who had high-risk prognostic 
factors. High-risk prognosis was defined as having at least 2 of the following 3 risk factors: (1) 
Gleason score of ≥8; (2) presence of 3 or more lesions on bone scan; (3) presence of measurable 
visceral (excluding lymph node disease) metastasis. In the active arm, ZYTIGA was administered at a 
dose of 1000 mg daily in combination with low dose prednisone 5 mg once daily in addition to ADT 
(LHRH agonist or orchiectomy), which was the standard of care treatment. Patients in the control arm 
received ADT and placebos for both ZYTIGA and prednisone. Study 302 enrolled docetaxel naïve 
patients; whereas, study 301 enrolled patients who had received prior docetaxel. Patients were using 
an LHRH analogue or were previously treated with orchiectomy. In the active treatment arm, 

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ZYTIGA was administered at a dose of 1,000 mg daily in combination with low dose prednisone or 
prednisolone 5 mg twice daily. Control patients received placebo and low dose prednisone or 
prednisolone 5 mg twice daily.

Changes in PSA serum concentration independently do not always predict clinical benefit. Therefore, 
in all studies it was recommended that patients be maintained on their study treatments until 
discontinuation criteria were met as specified below for each study.

In all studies spironolactone use was not allowed as spironolactone binds to the androgen receptor and 
may increase PSA levels.

Study 3011 (patients with newly diagnosed high risk mHSPC)
In Study 3011, (n=1199) the median age of enrolled patients was 67 years. The number of patients 
treated with ZYTIGA by racial group was Caucasian 832 (69.4%), Asian 246 (20.5%), Black or 
African American 25 (2.1%), other 80 (6.7%), unknown/not reported 13 (1.1%), and American Indian 
or Alaska Native 3 (0.3%). The ECOG performance status was 0 or 1 for 97% of patients. Patients 
with known brain metastasis, uncontrolled hypertension, significant heart disease, or NYHA Class II-
IV heart failure were excluded. Patients that were treated with prior pharmacotherapy, radiation 
therapy, or surgery for metastatic prostate cancer were excluded with the exception of up to 3 months 
of ADT or 1 course of palliative radiation or surgical therapy to treat symptoms resulting from 
metastatic disease. Co-primary efficacy endpoints were overall survival (OS) and radiographic 
progression-free survival (rPFS). The median baseline pain score, as measured by the Brief Pain 
Inventory Short Form (BPI-SF) was 2.0 in both the treatment and Placebo groups. In addition to the 
co-primary endpoint measures, benefit was also assessed using time to skeletal-related event (SRE), 
time to subsequent therapy for prostate cancer, time to initiation of chemotherapy, time to pain 
progression, and time to PSA progression. Treatment continued until disease progression, withdrawal 
of consent, the occurrence of unacceptable toxicity, or death.

Radiographic progression-free survival was defined as the time from randomization to the occurrence 
of radiographic progression or death from any cause. Radiographic progression included progression 
by bone scan (according to modified PCWG2) or progression of soft tissue lesions by CT or MRI 
(according to RECIST 1.1).

A significant difference in rPFS between treatment groups was observed (see Table 2 and Figure 1).

Table 2: Radiographic Progression-Free Survival – Stratified Analysis; Intent-to-treat Population 
(Study PCR3011)

AA-P Placebo
Subjects randomised 597 602

Event 239 (40.0%) 354 (58.8%)
Censored 358 (60.0%) 248 (41.2%)

Time to Event (months)
Median (95% CI) 33.02 (29.57, NE) 14.78 (14.69, 18.27)
Range (0.0+, 41.0+) (0.0+, 40.6+)

p valuea < 0.0001
Hazard ratio (95% CI)b 0.466 (0.394, 0.550)

Note: += censored observation, NE=not estimable. The radiographic progression and death are considered in 
defining the rPFS event. AA-P= subjects who received abiraterone acetate and prednisone.
a p value is from a log-rank test stratified by ECOG PS score (0/1 or 2) and visceral lesion (absent or present).
b Hazard ratio is from stratified proportional hazards model. Hazard ratio <1 favors AA-P.



12

Figure 1: Kaplan-Meier Plot of Radiographic Progression-free Survival; Intent-to-treat Population (Study 
PCR3011)

A statistically significant improvement in OS in favor of AA-P plus ADT was observed with a 34% 
reduction in the risk of death compared to Placebo plus ADT (HR=0.66; 95% CI: 0.56, 0.78; 
p<0.0001), (see Table 3 and Figure 2).

Table 3: Overall Survival of Patients Treated with Either ZYTIGA or Placebos in Study PCR3011
(Intent-to-Treat Analysis)

Overall Survival ZYTIGA with 
Prednisone

(N=597)

Placebos
(N=602)

Deaths (%) 275 (46%) 343 (57%)

Median survival (months)

(95% CI)

53.3 

(48.2, NE)

36.5 

(33.5, 40.0)

Hazard ratio (95% CI)1 0.66 (0.56, 0.78)
NE=Not estimable
1 Hazard Ratio is derived from a stratified proportional hazards model. Hazard ratio 1 favors ZYTIGA with 

prednisone.



13

Figure 2: Kaplan-Meier Plot of Overall Survival; Intent-to-treat Population in Study PCR3011 Analysis

Subgroup analyses consistently favor treatment with ZYTIGA. The treatment effect of AA-P on rPFS 
and OS across the pre-specified subgroups was favorable and consistent with the overall study 
population, except for the subgroup of ECOG score of 2 where no trend towards benefit was observed, 
however the small sample size (n=40) limits drawing any meaningful conclusion.

In addition to the observed improvements in overall survival and rPFS, benefit was demonstrated for 
ZYTIGA vs. placebo treatment in all prospectively-defined secondary endpoints.

Study 302 (chemotherapy naïve patients)
This study enrolled chemotherapy naïve patients who were asymptomatic or mildly symptomatic and 
for whom chemotherapy was not yet clinically indicated. A score of 0-1 on Brief Pain Inventory-Short 
Form (BPI-SF) worst pain in last 24 hours was considered asymptomatic, and a score of 2-3 was 
considered mildly symptomatic.

In study 302, (n = 1,088) the median age of enrolled patients was 71 years for patients treated with 
ZYTIGA plus prednisone or prednisolone and 70 years for patients treated with placebo plus 
prednisone or prednisolone. The number of patients treated with ZYTIGA by racial group was 
Caucasian 520 (95.4%), Black 15 (2.8%), Asian 4 (0.7%) and other 6 (1.1%). The Eastern Cooperative 
Oncology Group (ECOG) performance status was 0 for 76% of patients, and 1 for 24% of patients in 
both arms. Fifty percent of patients had only bone metastases, an additional 31% of patients had bone 
and soft tissue or lymph node metastases and 19% of patients had only soft tissue or lymph node 
metastases. Patients with visceral metastases were excluded. Co-primary efficacy endpoints were 
overall survival and radiographic progression-free survival (rPFS). In addition to the co-primary 
endpoint measures, benefit was also assessed using time to opiate use for cancer pain, time to initiation 
of cytotoxic chemotherapy, time to deterioration in ECOG performance score by ≥ 1 point and time to 
PSA progression based on Prostate Cancer Working Group-2 (PCWG2) criteria. Study treatments 
were discontinued at the time of unequivocal clinical progression. Treatments could also be 
discontinued at the time of confirmed radiographic progression at the discretion of the investigator.



14

Radiographic progression free survival (rPFS) was assessed with the use of sequential imaging studies 
as defined by PCWG2 criteria (for bone lesions) and modified Response Evaluation Criteria In Solid 
Tumors (RECIST) criteria (for soft tissue lesions). Analysis of rPFS utilised centrally-reviewed 
radiographic assessment of progression.

At the planned rPFS analysis there were 401 events, 150 (28%) of patients treated with ZYTIGA and 
251 (46%) of patients treated with placebo had radiographic evidence of progression or had died. A 
significant difference in rPFS between treatment groups was observed (see Table 4 and Figure 3).

Table 4: Study 302: Radiographic progression-free survival of patients treated with either 
ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH 
analogues or prior orchiectomy

ZYTIGA
(N = 546)

Placebo
(N = 542)

Radiographic 
Progression-free Survival 

(rPFS)
Progression or death 150 (28%) 251 (46%)

Median rPFS in months
(95% CI)

Not reached
(11.66; NE)

8.3
(8.12; 8.54)

p-value* < 0.0001
Hazard ratio** (95% CI) 0.425 (0.347; 0.522)

NE = Not estimated
* p-value is derived from a log-rank test stratified by baseline ECOG score (0 or 1)
** Hazard ratio < 1 favours ZYTIGA

Figure 3: Kaplan Meier curves of radiographic progression-free survival in patients treated 
with either ZYTIGA or placebo in combination with prednisone or prednisolone 
plus LHRH analogues or prior orchiectomy

AA = ZYTIGA

However, subject data continued to be collected through the date of the second interim analysis of 
Overall survival (OS). The investigator radiographic review of rPFS performed as a follow up 
sensitivity analysis is presented in Table 5 and Figure 4.



15

Six hundred and seven (607) subjects had radiographic progression or died: 271 (50%) in the 
abiraterone acetate group and 336 (62%) in the placebo group. Treatment with abiraterone acetate 
decreased the risk of radiographic progression or death by 47% compared with placebo 
(HR = 0.530; 95% CI: [0.451; 0.623], p < 0.0001). The median rPFS was 16.5 months in the 
abiraterone acetate group and 8.3 months in the placebo group.

Table 5: Study 302: Radiographic progression-free survival of patients treated with either 
ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH 
analogues or prior orchiectomy (At second interim analysis of OS-Investigator 
Review)

ZYTIGA
(N = 546)

Placebo
(N = 542)

Radiographic 
Progression-free Survival 

(rPFS)
Progression or death 271 (50%) 336 (62%)

Median rPFS in months
(95% CI)

16.5
(13.80; 16.79)

8.3
(8.05; 9.43)

p-value* < 0.0001
Hazard ratio**

(95% CI)
0.530 (0.451; 0.623)

* p-value is derived from a log-rank test stratified by baseline ECOG score (0 or 1)
** Hazard ratio < 1 favours ZYTIGA

Figure 4: Kaplan Meier curves of radiographic progression-free survival in patients treated 
with either ZYTIGA or placebo in combination with prednisone or prednisolone 
plus LHRH analogues or prior orchiectomy (At second interim analysis of 
OS-Investigator Review)

AA = ZYTIGA

A planned interim analysis (IA) for OS was conducted after 333 deaths were observed. The study was 
unblinded based on the magnitude of clinical benefit observed and patients in the placebo group were 
offered treatment with ZYTIGA. Overall survival was longer for ZYTIGA than placebo with a 25% 



16

reduction in risk of death (HR = 0.752; 95% CI: [0.606; 0.934], p = 0.0097), but OS was not mature 
and interim results did not meet the pre-specified stopping boundary for statistical significance (see 
Table 4). Survival continued to be followed after this IA.

The planned final analysis for OS was conducted after 741 deaths were observed (median follow up of 
49 months). Sixty-five percent (354 of 546) of patients treated with ZYTIGA, compared with 71% 
(387 of 542) of patients treated with placebo, had died. A statistically significant OS benefit in favour 
of the ZYTIGA-treated group was demonstrated with a 19.4% reduction in risk of death 
(HR = 0.806; 95% CI: [0.697; 0.931], p = 0.0033) and an improvement in median OS of 4.4 months 
(ZYTIGA 34.7 months, placebo 30.3 months) (see Table 6 and Figure 5). This improvement was 
demonstrated even though 44% of patients in the placebo arm received ZYTIGA as subsequent 
therapy.

Table 6: Study 302: Overall survival of patients treated with either ZYTIGA or placebo in 
combination with prednisone or prednisolone plus LHRH analogues or prior 
orchiectomy

ZYTIGA
(N = 546)

Placebo
(N = 542)

Interim survival analysis
Deaths (%) 147 (27%) 186 (34%)

Median survival (months)
(95% CI)

Not reached
(NE; NE)

27.2
(25.95; NE)

p-value* 0.0097
Hazard ratio** (95% CI) 0.752 (0.606; 0.934)
Final survival analysis

Deaths 354 (65%) 387 (71%)
Median overall survival in 

months (95% CI)
34.7 (32.7; 36.8) 30.3 (28.7; 33.3)

p-value* 0.0033
Hazard ratio** (95% CI) 0.806 (0.697; 0.931)

NE = Not Estimated
* p-value is derived from a log-rank test stratified by baseline ECOG score (0 or 1)
** Hazard ratio < 1 favours ZYTIGA



17

Figure 5: Kaplan Meier survival curves of patients treated with either ZYTIGA or placebo in 
combination with prednisone or prednisolone plus LHRH analogues or prior 
orchiectomy, final analysis

AA = ZYTIGA

In addition to the observed improvements in overall survival and rPFS, benefit was demonstrated for 
ZYTIGA vs. placebo treatment in all secondary endpoint measures as follows:

Time to PSA progression based on PCWG2 criteria: The median time to PSA progression was 
11.1 months for patients receiving ZYTIGA and 5.6 months for patients receiving placebo 
(HR = 0.488; 95% CI: [0.420; 0.568], p < 0.0001). The time to PSA progression was approximately 
doubled with ZYTIGA treatment (HR = 0.488). The proportion of subjects with a confirmed PSA 
response was greater in the ZYTIGA group than in the placebo group (62% vs. 24%; p < 0.0001). In 
subjects with measurable soft tissue disease, significantly increased numbers of complete and partial 
tumor responses were seen with ZYTIGA treatment.

Time to opiate use for cancer pain: The median time to opiate use for prostate cancer pain at the time 
of final analysis was 33.4 months for patients receiving ZYTIGA and was 23.4 months for patients 
receiving placebo (HR = 0.721; 95% CI: [0.614; 0.846], p < 0.0001).

Time to initiation of cytotoxic chemotherapy: The median time to initiation of cytotoxic chemotherapy 
was 25.2 months for patients receiving ZYTIGA and 16.8 months for patients receiving placebo 
(HR = 0.580; 95% CI: [0.487; 0.691], p < 0.0001).

Time to deterioration in ECOG performance score by ≥ 1 point: The median time to deterioration in 
ECOG performance score by ≥ 1 point was 12.3 months for patients receiving ZYTIGA and 
10.9 months for patients receiving placebo (HR = 0.821; 95% CI: [0.714; 0.943], p = 0.0053).

The following study endpoints demonstrated a statistically significant advantage in favour of ZYTIGA 
treatment:



18

Objective response: Objective response was defined as the proportion of subjects with measurable 
disease achieving a complete or partial response according to RECIST criteria (baseline lymph node 
size was required to be ≥ 2 cm to be considered a target lesion). The proportion of subjects with 
measurable disease at baseline who had an objective response was 36% in the ZYTIGA group and 
16% in the placebo group (p < 0.0001).

Pain: Treatment with ZYTIGA significantly reduced the risk of average pain intensity progression by 
18% compared with placebo (p = 0.0490). The median time to progression was 26.7 months in the 
ZYTIGA group and 18.4 months in the placebo group.

Time to degradation in the FACT-P (Total Score): Treatment with ZYTIGA decreased the risk of 
FACT-P (Total Score) degradation by 22% compared with placebo (p = 0.0028). The median time to 
degradation in FACT-P (Total Score) was 12.7 months in the ZYTIGA group and 8.3 months in the 
placebo group.

Study 301 (patients who had received prior chemotherapy)
Study 301 enrolled patients who had received prior docetaxel. Patients were not required to show 
disease progression on docetaxel, as toxicity from this chemotherapy may have led to discontinuation.
Patients were maintained on study treatments until there was PSA progression (confirmed 25% 
increase over the patient’s baseline/nadir) together with protocol-defined radiographic progression and 
symptomatic or clinical progression. Patients with prior ketoconazole treatment for prostate cancer 
were excluded from this study. The primary efficacy endpoint was overall survival.

The median age of enrolled patients was 69 years (range 39-95). The number of patients treated with 
ZYTIGA by racial group was Caucasian 737 (93.2%), Black 28 (3.5%), Asian 11 (1.4%) and other 14 
(1.8%). Eleven percent of patients enrolled had an ECOG performance score of 2; 70% had 
radiographic evidence of disease progression with or without PSA progression; 70% had received one 
prior cytotoxic chemotherapy and 30% received two. Liver metastasis was present in 11% of patients 
treated with ZYTIGA.

In a planned analysis conducted after 552 deaths were observed, 42% (333 of 797) of patients treated 
with ZYTIGA compared with 55% (219 of 398) of patients treated with placebo, had died. A 
statistically significant improvement in median overall survival was seen in patients treated with 
ZYTIGA (see Table 7).

Table 7: Overall survival of patients treated with either ZYTIGA or placebo in 
combination with prednisone or prednisolone plus LHRH analogues or prior 
orchiectomy

ZYTIGA
(N = 797)

Placebo
(N = 398)

Primary Survival Analysis
Deaths (%) 333 (42%) 219 (55%)

Median survival (months)
(95% CI)

14.8 (14.1; 15.4) 10.9 (10.2; 12.0)

p-valuea < 0.0001
Hazard ratio (95% CI)b 0.646 (0.543; 0.768)

Updated Survival Analysis
Deaths (%) 501 (63%) 274 (69%)

Median survival (months)
(95% CI)

15.8 (14.8; 17.0) 11.2 (10.4; 13.1)

Hazard ratio (95% CI)b 0.740 (0.638; 0.859)
a p-value is derived from a log-rank test stratified by ECOG performance status score (0-1 vs. 2), pain score (absent vs. 

present), number of prior chemotherapy regimens (1 vs. 2), and type of disease progression (PSA only vs. 
radiographic).

b Hazard ratio is derived from a stratified proportional hazards model. Hazard ratio < 1 favours ZYTIGA



19

At all evaluation time points after the initial few months of treatment, a higher proportion of patients 
treated with ZYTIGA remained alive, compared with the proportion of patients treated with placebo
(see Figure 6).

Figure 6: Kaplan Meier survival curves of patients treated with either ZYTIGA or placebo in 
combination with prednisone or prednisolone plus LHRH analogues or prior 
orchiectomy

AA = ZYTIGA



20

Subgroup survival analyses showed a consistent survival benefit for treatment with ZYTIGA (see 
Figure 7).

Figure 7: Overall survival by subgroup: hazard ratio and 95% confidence interval

AA = ZYTIGA; BPI = Brief Pain Inventory; C.I. = confidence interval; ECOG = Eastern Cooperative Oncology Group 
performance score; HR = hazard ratio; NE = not evaluable

In addition to the observed improvement in overall survival, all secondary study endpoints favoured 
ZYTIGA and were statistically significant after adjusting for multiple testing as follows:

Patients receiving ZYTIGA demonstrated a significantly higher total PSA response rate (defined as a 
≥ 50% reduction from baseline), compared with patients receiving placebo, 38% vs. 10%, p < 0.0001.

The median time to PSA progression was 10.2 months for patients treated with ZYTIGA and 
6.6 months for patients treated with placebo (HR = 0.580; 95% CI: [0.462; 0.728], p < 0.0001).

The median radiographic progression-free survival was 5.6 months for patients treated with ZYTIGA 
and 3.6 months for patients who received placebo (HR = 0.673; 95% CI: [0.585; 0.776], p < 0.0001).

Pain
The proportion of patients with pain palliation was statistically significantly higher in the ZYTIGA 
group than in the placebo group (44% vs. 27%, p = 0.0002). A responder for pain palliation was 
defined as a patient who experienced at least a 30% reduction from baseline in the BPI-SF worst pain 
intensity score over the last 24 hours without any increase in analgesic usage score observed at 
two consecutive evaluations four weeks apart. Only patients with a baseline pain score of ≥ 4 and at 
least one post-baseline pain score were analysed (N = 512) for pain palliation.

A lower proportion of patients treated with ZYTIGA had pain progression compared to patients taking 
placebo at 6 (22% vs. 28%), 12 (30% vs. 38%) and 18 months (35% vs. 46%). Pain progression was 
defined as an increase from baseline of ≥ 30% in the BPI-SF worst pain intensity score over the 
previous 24 hours without a decrease in analgesic usage score observed at two consecutive visits, or an 
increase of ≥ 30% in analgesic usage score observed at two consecutive visits. The time to pain 
progression at the 25th percentile was 7.4 months in the ZYTIGA group, versus 4.7 months in the 
placebo group.



21

Skeletal-related events
A lower proportion of patients in the ZYTIGA group had skeletal-related events compared with the 
placebo group at 6 months (18% vs. 28%), 12 months (30% vs. 40%), and 18 months (35% vs. 40%). 
The time to first skeletal-related event at the 25th percentile in the ZYTIGA group was twice that of the 
control group at 9.9 months versus 4.9 months. A skeletal-related event was defined as a pathological 
fracture, spinal cord compression, palliative radiation to bone, or surgery to bone.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with 
ZYTIGA in all subsets of the paediatric population in advanced prostate cancer. See section 4.2 for 
information on paediatric use.

5.2 Pharmacokinetic properties

Following administration of abiraterone acetate, the pharmacokinetics of abiraterone and abiraterone 
acetate have been studied in healthy subjects, patients with metastatic advanced prostate cancer and 
subjects without cancer with hepatic or renal impairment. Abiraterone acetate is rapidly converted in 
vivo to abiraterone, an androgen biosynthesis inhibitor (see section 5.1).

Absorption
Following oral administration of abiraterone acetate in the fasting state, the time to reach maximum 
plasma abiraterone concentration is approximately 2 hours.

Administration of abiraterone acetate with food, compared with administration in a fasted state, results 
in up to a 10-fold (AUC) and up to a 17-fold (Cmax) increase in mean systemic exposure of abiraterone, 
depending on the fat content of the meal. Given the normal variation in the content and composition of 
meals, taking ZYTIGA with meals has the potential to result in highly variable exposures. Therefore, 
ZYTIGA must not be taken with food. It should be taken at least one hour before or at least two hours 
after eating. The tablets should be swallowed whole with water (see section 4.2).

Distribution
The plasma protein binding of 14C-abiraterone in human plasma is 99.8%. The apparent volume of 
distribution is approximately 5,630 l, suggesting that abiraterone extensively distributes to peripheral 
tissues.

Biotransformation
Following oral administration of 14C-abiraterone acetate as capsules, abiraterone acetate is hydrolysed 
to abiraterone, which then undergoes metabolism including sulphation, hydroxylation and oxidation 
primarily in the liver. The majority of circulating radioactivity (approximately 92%) is found in the 
form of metabolites of abiraterone. Of 15 detectable metabolites, 2 main metabolites, abiraterone 
sulphate and N-oxide abiraterone sulphate, each represents approximately 43% of total radioactivity.

Elimination
The mean half-life of abiraterone in plasma is approximately 15 hours based on data from healthy 
subjects. Following oral administration of 14C-abiraterone acetate 1,000 mg, approximately 88% of the 
radioactive dose is recovered in faeces and approximately 5% in urine. The major compounds present 
in faeces are unchanged abiraterone acetate and abiraterone (approximately 55% and 22% of the 
administered dose, respectively).

Hepatic impairment
The pharmacokinetics of abiraterone acetate was examined in subjects with pre-existing mild or 
moderate hepatic impairment (Child-Pugh Class A and B, respectively) and in healthy control 
subjects. Systemic exposure to abiraterone after a single oral 1,000 mg dose increased by 
approximately 11% and 260% in subjects with mild and moderate pre-existing hepatic impairment, 
respectively. The mean half-life of abiraterone is prolonged to approximately 18 hours in subjects with 
mild hepatic impairment and to approximately 19 hours in subjects with moderate hepatic impairment.



22

In another trial, the pharmacokinetics of abiraterone were examined in subjects with pre-existing 
severe (n = 8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal 
hepatic function. The AUC to abiraterone increased by approximately 600% and the fraction of free 
drug increased by 80% in subjects with severe hepatic impairment compared to subjects with normal 
hepatic function.

No dose adjustment is necessary for patients with pre-existing mild hepatic impairment.
The use of abiraterone acetate 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 4.4). 
abiraterone acetate should not be used in patients with severe hepatic impairment (see sections 4.2, 4.3 
and 4.4).

For patients who develop hepatotoxicity during treatment, suspension of treatment and dose 
adjustment may be required (see sections 4.2 and 4.4).

Renal impairment
The pharmacokinetics of abiraterone acetate was compared in patients with end-stage renal disease on 
a stable haemodialysis schedule versus matched control subjects with normal renal function. Systemic 
exposure to abiraterone after a single oral 1,000 mg dose did not increase in subjects with end-stage 
renal disease on dialysis. Administration in patients with renal impairment, including severe renal 
impairment, does not require dose reduction (see section 4.2). However, there is no clinical experience 
in patients with prostate cancer and severe renal impairment. Caution is advised in these patients.

5.3 Preclinical safety data

In all animal toxicity studies, circulating testosterone levels were significantly reduced. As a result, 
reduction in organ weights and morphological and/or histopathological changes in the reproductive 
organs, and the adrenal, pituitary and mammary glands were observed. All changes showed complete 
or partial reversibility. The changes in the reproductive organs and androgen-sensitive organs are 
consistent with the pharmacology of abiraterone. All treatment-related hormonal changes reversed or 
were shown to be resolving after a 4-week recovery period.

In fertility studies in both male and female rats, abiraterone acetate reduced fertility, which was 
completely reversible in 4 to 16 weeks after abiraterone acetate was stopped.

In a developmental toxicity study in the rat, abiraterone acetate affected pregnancy including reduced 
foetal weight and survival. Effects on the external genitalia were observed though abiraterone acetate 
was not teratogenic.

In these fertility and developmental toxicity studies performed in the rat, all effects were related to the 
pharmacological activity of abiraterone.

Aside from reproductive organ changes seen in all animal toxicology studies, non-clinical data reveal 
no special hazard for humans based on conventional studies of safety pharmacology, repeated dose 
toxicity, genotoxicity and carcinogenic potential. Abiraterone acetate was not carcinogenic in a 
6-month study in the transgenic (Tg.rasH2) mouse. In a 24-month carcinogenicity study in the rat, 
abiraterone acetate increased the incidence of interstitial cell neoplasms in the testes. This finding is 
considered related to the pharmacological action of abiraterone and rat specific. Abiraterone acetate 
was not carcinogenic in female rats.

The active substance, abiraterone, shows an environmental risk for the aquatic environment, especially 
to fish.



23

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose
Croscarmellose sodium
Lactose monohydrate
Magnesium stearate
Povidone (K29/K32)
Colloidal anhydrous silica
Sodium laurilsulfate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

6.4 Special precautions for storage

This medicinal product does not require special storage conditions.

6.5 Nature and contents of container

Round white HDPE bottles fitted with a polypropylene child-resistant closure containing 120 tablets. 
Each pack contains one bottle.

6.6 Special precautions for disposal and other handling

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).

7. MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/714/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 05 September 2011

Date of latest renewal: 26 May 2016



24

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

http://www.ema.europa.eu/


25

1. NAME OF THE MEDICINAL PRODUCT

ZYTIGA 500 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 500 mg of abiraterone acetate.

Excipients with known effect
Each film-coated tablet contains 253.2 mg of lactose and 13.5 mg of sodium.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet
Purple, oval-shaped, film-coated tablets (20 mm long by 10 mm wide), debossed with “AA” on one 
side and “500” on the other side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

ZYTIGA is indicated with prednisone or prednisolone for:
 the treatment of newly diagnosed high risk metastatic hormone sensitive prostate cancer 

(mHSPC) in adult men in combination with androgen deprivation therapy (ADT) (see section 
5.1)

 the treatment of metastatic castration resistant prostate cancer (mCRPC) in adult men who are 
asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom 
chemotherapy is not yet clinically indicated (see section 5.1)

 the treatment of mCRPC in adult men whose disease has progressed on or after a 
docetaxel-based chemotherapy regimen.

4.2 Posology and method of administration

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

Posology
The recommended dose is 1,000 mg (two 500 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 



26

should 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 (one tablet) 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.

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
- Women who are or may potentially be pregnant (see section 4.6).
- Severe hepatic impairment [Child-Pugh Class C (see sections 4.2, 4.4 and 5.2)].
- ZYTIGA with prednisone or prednisolone is contraindicated in combination with Ra-223.



27

4.4 Special warnings and precautions for use

Hypertension, hypokalaemia, fluid retention and cardiac failure due to mineralocorticoid excess
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).

ZYTIGA should be used with caution in patients with a history of cardiovascular disease. The Phase 3 
studies 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 (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 4.8 and 5.1).

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, 
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 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 4.2).

Hepatotoxicity and hepatic impairment
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 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 4.2).

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 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 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 4.2, 4.3 and 5.2).

There have been rare post-marketing reports of acute liver failure and hepatitis fulminant, some with 
fatal outcome (see section 4.8).



28

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

In patients on prednisone or prednisolone 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 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 plus prednisone/prednisolone 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 with cytotoxic chemotherapy has not been 
established (see section 5.1).

Intolerance to excipients
This medicinal product contains lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicine. This medicinal product also contains more than 1.18 mmol (or 27 mg) sodium per dose of 
two tablets. To be taken into consideration by patients on a controlled sodium diet.

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

Skeletal muscle effects
Cases of myopathy and rhabdomyolysis have been reported in patients treated with ZYTIGA. Most 
cases developed within the first 6 months of treatment and recovered after ZYTIGA 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 4.5).

Combination of abiraterone and prednisone/prednisolone with Ra-223
Treatment with abiraterone and prednisone/prednisolone in combination with Ra-223 is 
contraindicated (see section 4.3) 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.



29

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

4.5 Interaction with other medicinal products and other forms of interaction

Effect of food on abiraterone acetate
Administration with food significantly increases the absorption of abiraterone acetate. The efficacy 
and safety when given with food have not been established therefore this medicinal product must not 
be taken with food (see sections 4.2 and 5.2).

Interactions with other medicinal products
Potential for other medicinal products to affect abiraterone exposures
In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 
inducer rifampicin, 600 mg daily for 6 days followed by a single dose of abiraterone acetate 1,000 mg, 
the mean plasma AUC∞ of abiraterone was decreased by 55%.

Strong inducers of CYP3A4 (e.g., phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, 
phenobarbital, St John’s wort [Hypericum perforatum]) during treatment are to be avoided, unless 
there is no therapeutic alternative.

In a separate clinical pharmacokinetic interaction study of healthy subjects, co-administration of 
ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the 
pharmacokinetics of abiraterone.

Potential to affect exposures to other medicinal products
Abiraterone is an inhibitor of the hepatic drug-metabolising enzymes CYP2D6 and CYP2C8.
In a study to determine the effects of abiraterone acetate (plus prednisone) on a single dose of the 
CYP2D6 substrate dextromethorphan, the systemic exposure (AUC) of dextromethorphan was 
increased approximately 2.9 fold. The AUC24 for dextrorphan, the active metabolite of 
dextromethorphan, increased approximately 33%.

Caution is advised when administering with medicinal products activated by or metabolised by 
CYP2D6, particularly with medicinal products that have a narrow therapeutic index. Dose reduction of 
medicinal products with a narrow therapeutic index that are metabolised by CYP2D6 should be 
considered. Examples of medicinal products metabolised by CYP2D6 include metoprolol, 
propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecainide, codeine, 
oxycodone and tramadol (the latter three medicinal products requiring CYP2D6 to form their active 
analgesic metabolites).

In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone was increased by 
46% and the AUCs for M-III and M-IV, the active metabolites of pioglitazone, each decreased by 10% 
when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Patients 
should be monitored for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic 
index if used concomitantly. Examples of medicinal products metabolised by CYP2C8 include 
pioglitazone and repaglinide (see section 4.4).

In vitro, the major metabolites abiraterone sulphate and N-oxide abiraterone sulphate were shown to 
inhibit the hepatic uptake transporter OATP1B1 and as a consequence it may increase the 
concentrations of medicinal products eliminated by OATP1B1. There are no clinical data available to 
confirm transporter based interaction.

Use with products known to prolong QT interval
Since androgen deprivation treatment may prolong the QT interval, caution is advised when 
administering ZYTIGA with medicinal products known to prolong the QT interval or medicinal 
products able to induce torsades de pointes such as class IA (e.g. quinidine, disopyramide) or class III 
(e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, 
moxifloxacin, antipsychotics, etc.



30

Use with Spironolactone
Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels. 
Use with ZYTIGA is not recommended (see section 5.1).

4.6 Fertility, pregnancy and lactation

Women of childbearing potential
There are no human data on the use of ZYTIGA in pregnancy and this medicinal product is not for use 
in women of childbearing potential.

Contraception in males and females
It is not known whether abiraterone or its metabolites are present in semen. A condom is required if 
the patient is engaged in sexual activity with a pregnant woman. If the patient is engaged in sex with a 
woman of childbearing potential, a condom is required along with another effective contraceptive 
method. Studies in animals have shown reproductive toxicity (see section 5.3).

Pregnancy
ZYTIGA is not for use in women and 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.

Fertility
Abiraterone affected fertility in male and female rats, but these effects were fully reversible (see 
section 5.3).

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

Summary of the safety profile
In an analysis of adverse reactions of composite Phase 3 studies with ZYTIGA, adverse reactions that 
were observed in ≥10% of patients were peripheral oedema, hypokalaemia, hypertension urinary tract 
infection, and alanine aminotransferase increased and/or aspartate aminotransferase increased.
Other important adverse reactions include, cardiac disorders, hepatotoxicity, fractures, and allergic 
alveolitis.

ZYTIGA may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic 
consequence of its mechanism of action. In Phase 3 studies, anticipated mineralocorticoid adverse 
reactions were seen more commonly in patients treated with abiraterone acetate than in patients treated 
with placebo: hypokalaemia 18% vs. 8%, hypertension 22% vs. 16% and fluid retention (peripheral 
oedema) 23% vs. 17%, respectively. In patients treated with abiraterone acetate versus patients treated 
with placebo: CTCAE (version 4.0) Grades 3 and 4 hypokalaemia were observed in 6% versus 1%, 
CTCAE (version 4.0) Grades 3 and 4 hypertension were observed in 7% versus 5%, and fluid 
retention (peripheral oedema) Grades 3 and 4 were observed in 1% versus 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 list of adverse reactions
In studies of patients with metastatic advanced prostate cancer who were using an LHRH analogue, or 
were previously treated with orchiectomy, ZYTIGA was administered at a dose of 1,000 mg daily in 



31

combination with low dose prednisone or prednisolone (either 5 or 10 mg daily depending on the 
indication).

Adverse reactions observed during clinical studies and post-marketing experience 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) and not known (frequency cannot be estimated from the available data).

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

Table 1: Adverse reactions identified in clinical studies and post-marketing
System Organ Class Adverse reaction and frequency
Infections and infestations very common: urinary tract infection

common: sepsis
Immune system disorders not known: anaphylactic reactions
Endocrine disorders uncommon: adrenal insufficiency
Metabolism and nutrition disorders very common: hypokalaemia

common: hypertriglyceridaemia
Cardiac disorders common: cardiac failure*, angina pectoris, 

atrial fibrillation, tachycardia
uncommon: other arrhythmias
not known: myocardial infarction, 
QT prolongation (see sections 4.4 and 4.5)

Vascular disorders very common: hypertension
Respiratory, thoracic and mediastinal 
disorders

rare: allergic alveolitisa

Gastrointestinal disorders very common: diarrhoea
common: dyspepsia

Hepatobiliary disorders very common: alanine aminotransferase
increased and/or aspartate aminotransferase 
increased b

rare: hepatitis fulminant, acute hepatic failure
Skin and subcutaneous tissue disorders common: rash
Musculoskeletal and connective tissue 
disorders

uncommon: myopathy, rhabdomyolysis

Renal and urinary disorders common: haematuria
General disorders and administration site 
conditions

very common: oedema peripheral

Injury, poisoning and procedural 
complications

common: fractures**

* Cardiac failure also includes congestive heart failure, left ventricular dysfunction and ejection fraction decreased
** Fractures includes osteoporosis and all fractures with the exception of pathological fractures
a Spontaneous reports from post-marketing experience
b Alanine aminotransferase increased and/or aspartate aminotransferase increased includes ALT increased, AST 

increased, and hepatic function abnormal.

The following CTCAE (version 4.0) Grade 3 adverse reactions occurred in patients treated with 
abiraterone acetate: hypokalaemia 5%; urinary tract infection 2%; alanine aminotransferase increased
and/or aspartate aminotransferase increased 4%; hypertension 6%; fractures 2%; peripheral oedema, 
cardiac failure, and atrial fibrillation 1% each. CTCAE (version 4.0) Grade 3 hypertriglyceridaemia 
and angina pectoris occurred in < 1% of patients. CTCAE (version 4.0) Grade 4 urinary tract infection,
alanine aminotransferase increased and/or aspartate aminotransferase increased, hypokalemia, cardiac 
failure, atrial fibrillation, and fractures occurred in < 1% of patients.

A higher incidence of hypertension and hypokalemia was observed in the hormone sensitive 
population (study 3011). Hypertension was reported in 36.7% of patients in the hormone sensitive 
population (study 3011) compared to 11.8% and 20.2% in studies 301 and 302, respectively. 



32

Hypokalemia was observed in 20.4% of patients in the hormone sensitive population (study 3011) 
compared to 19.2% and 14.9% in 301 and 302, respectively).

The incidence and severity of adverse events was higher in the subgroup of patients with baseline 
ECOG2 performance status grade and also in elderly patients (≥75 years ).

Description of selected adverse reactions
Cardiovascular reactions
The three Phase 3 studies 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 NYHA Class 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%. All patients enrolled 
(both active and placebo-treated patients) were concomitantly treated with androgen deprivation 
therapy, predominantly with the use of LHRH analogues, which has been associated with diabetes, 
myocardial infarction, cerebrovascular accident and sudden cardiac death. The incidence of 
cardiovascular adverse reactions in the Phase 3 studies in patients taking abiraterone acetate versus 
patients taking placebo were as follows: atrial fibrillation 2.6% vs. 2.0%, tachycardia 1.9% vs. 1.0%, 
angina pectoris 1.7% vs. 0.8%, cardiac failure 0.7% vs. 0.2%, and arrhythmia 0.7% vs. 0.5%.

Hepatotoxicity
Hepatotoxicity with elevated ALT, AST and total bilirubin has been reported in patients treated with 
abiraterone acetate. Across Phase 3 clinical studies, hepatotoxicity grades 3 and 4 (e.g., ALT or AST 
increases of > 5 x ULN or bilirubin increases > 1.5 x ULN) were reported in approximately 6% of 
patients who received abiraterone acetate, typically during the first 3 months after starting treatment. 
In Study 3011, grade 3 or 4 hepatotoxicity was observed in 8.4% of patients treated with ZYTIGA. 
Ten patients who received ZYTIGA were discontinued because of hepatotoxicity; two had Grade 2 
hepatotoxicity, six had Grade 3 hepatotoxicity, and two had Grade 4 hepatotoxicity. No patient died of 
hepatotoxicity in Study 3011. In the Phase 3 clinical studies, patients whose baseline ALT or AST 
were elevated were more likely to experience liver function test elevations than those beginning with 
normal values. When elevations of either ALT or AST > 5 x ULN, or elevations in bilirubin 
> 3 x ULN were observed, abiraterone acetate was withheld or discontinued. In two instances marked 
increases in liver function tests occurred (see section 4.4). These two patients with normal baseline 
hepatic function, experienced ALT or AST elevations 15 to 40 x ULN and bilirubin elevations 2 to 
6 x ULN. Upon discontinuation of treatment, both patients had normalisation of their liver function 
tests and one patient was re-treated without recurrence of the elevations. In study 302, Grade 3 or 4 
ALT or AST elevations were observed in 35 (6.5%) patients treated with abiraterone acetate. 
Aminotransferase elevations resolved in all but 3 patients (2 with new multiple liver metastases and 1 
with AST elevation approximately 3 weeks after the last dose of abiraterone acetate). In Phase 3 
clinical studies, treatment discontinuations due to ALT and AST increases or abnormal hepatic 
function were reported in 1.1% of patients treated with abiraterone acetate and 0.6% of patients treated 
with placebo; no deaths were reported due to hepatotoxicity events.

In clinical trials, the risk for hepatotoxicity was mitigated by exclusion of patients with baseline 
hepatitis or significant abnormalities of liver function tests. In the 3011 trial, patients with baseline 
ALT and AST > 2.5 X ULN, bilirubin > 1.5 X ULN or those with active or symptomatic viral 
hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction were
excluded. In the 301 trial, patients with baseline ALT and AST ≥ 2.5 x ULN in the absence of liver 
metastases and > 5 x ULN in the presence of liver metastases were excluded. In the 302 trial, patients 
with liver metastases were not eligible and patients with baseline ALT and AST ≥ 2.5 x ULN were 
excluded. Abnormal liver function tests developing in patients participating in clinical trials were 
vigorously managed by requiring treatment interruption and permitting re-treatment only after return 
of liver function tests to the patient’s baseline (see section 4.2). Patients with elevations of ALT or 
AST > 20 x ULN were not re-treated. The safety of re-treatment in such patients is unknown. The 
mechanism for hepatotoxicity is not understood.



33

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

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.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: endocrine therapy, other hormone antagonists and related agents, ATC 
code: L02BX03

Mechanism of action
Abiraterone acetate (ZYTIGA) is converted in vivo to abiraterone, an androgen biosynthesis inhibitor. 
Specifically, abiraterone selectively inhibits the enzyme 17α-hydroxylase/C17,20-lyase (CYP17). This 
enzyme is expressed in and is required for androgen biosynthesis in testicular, adrenal and prostatic 
tumour tissues. CYP17 catalyses the conversion of pregnenolone and progesterone into testosterone 
precursors, DHEA and androstenedione, respectively, by 17α-hydroxylation and cleavage of the 
C17,20 bond. CYP17 inhibition also results in increased mineralocorticoid production by the adrenals 
(see section 4.4).

Androgen-sensitive prostatic carcinoma responds to treatment that decreases androgen levels. 
Androgen deprivation therapies, such as treatment with LHRH analogues or orchiectomy, decrease 
androgen production in the testes but do not affect androgen production by the adrenals or in the 
tumour. Treatment with ZYTIGA decreases serum testosterone to undetectable levels (using 
commercial assays) when given with LHRH analogues (or orchiectomy).

Pharmacodynamic effects
ZYTIGA decreases serum testosterone and other androgens to levels lower than those achieved by the 
use of LHRH analogues alone or by orchiectomy. This results from the selective inhibition of the 
CYP17 enzyme required for androgen biosynthesis. PSA serves as a biomarker in patients with 
prostate cancer. In a Phase 3 clinical study of patients who failed prior chemotherapy with taxanes, 
38% of patients treated with abiraterone acetate, versus 10% of patients treated with placebo, had at 
least a 50% decline from baseline in PSA levels.

Clinical efficacy and safety
Efficacy was established in three randomised placebo-controlled multicentre Phase 3 clinical studies 
(studies 3011, 302 and 301) of patients with mHSPC and mCRPC. Study 3011 enrolled patients who 
were newly diagnosed (within 3 months of randomization) mHSPC who had high-risk prognostic 
factors. High-risk prognosis was defined as having at least 2 of the following 3 risk factors: (1) 
Gleason score of ≥8; (2) presence of 3 or more lesions on bone scan; (3) presence of measurable 
visceral (excluding lymph node disease) metastasis. In the active arm, ZYTIGA was administered at a 
dose of 1000 mg daily in combination with low dose prednisone 5 mg once daily in addition to ADT 
(LHRH agonist or orchiectomy), which was the standard of care treatment. Patients in the control arm 
received ADT and placebos for both ZYTIGA and prednisone. Study 302 enrolled docetaxel naïve 
patients; whereas, study 301 enrolled patients who had received prior docetaxel. Patients were using 
an LHRH analogue or were previously treated with orchiectomy. In the active treatment arm, 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


34

ZYTIGA was administered at a dose of 1,000 mg daily in combination with low dose prednisone or 
prednisolone 5 mg twice daily. Control patients received placebo and low dose prednisone or 
prednisolone 5 mg twice daily.

Changes in PSA serum concentration independently do not always predict clinical benefit. Therefore, 
in all studies it was recommended that patients be maintained on their study treatments until 
discontinuation criteria were met as specified below for each study.

In all studies spironolactone use was not allowed as spironolactone binds to the androgen receptor and 
may increase PSA levels.

Study 3011 (patients with newly diagnosed high risk mHSPC)
In Study 3011, (n=1199) the median age of enrolled patients was 67 years. The number of patients 
treated with ZYTIGA by racial group was Caucasian 832 (69.4%), Asian 246 (20.5%), Black or 
African American 25 (2.1%), other 80 (6.7%), unknown/not reported 13 (1.1%), and American Indian 
or Alaska Native 3 (0.3%). The ECOG performance status was 0 or 1 for 97% of patients. Patients 
with known brain metastasis, uncontrolled hypertension, significant heart disease, or NYHA Class II-
IV heart failure were excluded. Patients that were treated with prior pharmacotherapy, radiation 
therapy, or surgery for metastatic prostate cancer were excluded with the exception of up to 3 months 
of ADT or 1 course of palliative radiation or surgical therapy to treat symptoms resulting from 
metastatic disease. Co-primary efficacy endpoints were overall survival (OS) and radiographic 
progression-free survival (rPFS). The median baseline pain score, as measured by the Brief Pain 
Inventory Short Form (BPI-SF) was 2.0 in both the treatment and Placebo groups. In addition to the 
co-primary endpoint measures, benefit was also assessed using time to skeletal-related event (SRE), 
time to subsequent therapy for prostate cancer, time to initiation of chemotherapy, time to pain 
progression, and time to PSA progression. Treatment continued until disease progression, withdrawal 
of consent, the occurrence of unacceptable toxicity, or death.

Radiographic progression-free survival was defined as the time from randomization to the occurrence 
of radiographic progression or death from any cause. Radiographic progression included progression 
by bone scan (according to modified PCWG2) or progression of soft tissue lesions by CT or MRI 
(according to RECIST 1.1).

A significant difference in rPFS between treatment groups was observed (see Table 2 and Figure 1).

Table 2: Radiographic Progression-Free Survival - Stratified Analysis; Intent-to-treat Population 
(Study PCR3011)

AA-P Placebo
Subjects randomised 597 602

Event 239 (40.0%) 354 (58.8%)
Censored 358 (60.0%) 248 (41.2%)

Time to Event (months)
Median (95% CI) 33.02 (29.57, NE) 14.78 (14.69, 18.27)
Range (0.0+, 41.0+) (0.0+, 40.6+)

p valuea < 0.0001
Hazard ratio (95% CI)b 0.466 (0.394, 0.550)

Note: += censored observation, NE=not estimable. The radiographic progression and death are considered in 
defining the rPFS event. AA-P= subjects who received abiraterone acetate and prednisone.
a p value is from a log-rank test stratified by ECOG PS score (0/1 or 2) and visceral lesion (absent or present).
b Hazard ratio is from stratified proportional hazards model. Hazard ratio <1 favors AA-P.



35

Figure 1: Kaplan-Meier Plot of Radiographic Progression-free Survival; Intent-to-treat Population (Study 
PCR3011)

A statistically significant improvement in OS in favor of AA-P plus ADT was observed with a 34% 
reduction in the risk of death compared to Placebo plus ADT (HR=0.66; 95% CI: 0.56, 0.78; 
p<0.0001, (see Table 3 and Figure 2).

Table 3: Overall Survival of Patients Treated with Either ZYTIGA or Placebos in Study PCR3011
(Intent-to-Treat Analysis)

Overall Survival ZYTIGA with Prednisone
(N=597)

Placebos
(N=602)

Deaths (%) 275 (46%) 343 (57%)
Median survival (months)

(95% CI)
53.3

(48.2, NE)
36.5

(33.5, 40.0)
Hazard ratio (95% CI)1 0.66 (0.56, 0.78)

NE=Not estimable
1 Hazard Ratio is derived from a stratified proportional hazards model. Hazard ratio 1 favors ZYTIGA 
with prednisone.



36

Figure 2: Kaplan-Meier Plot of Overall Survival; Intent-to-treat Population in Study PCR3011 Analysis

Subgroup analyses consistently favor treatment with ZYTIGA. The treatment effect of AA-P on rPFS 
and OS across the pre-specified subgroups was favorable and consistent with the overall study 
population, except for the subgroup of ECOG score of 2 where no trend towards benefit was observed, 
however the small sample size (n=40) limits drawing any meaningful conclusion.

In addition to the observed improvements in overall survival and rPFS, benefit was demonstrated for 
ZYTIGA vs. placebo treatment in all prospectively-defined secondary endpoints.

Study 302 (chemotherapy naïve patients)
This study enrolled chemotherapy naïve patients who were asymptomatic or mildly symptomatic and 
for whom chemotherapy was not yet clinically indicated. A score of 0-1 on Brief Pain Inventory-Short 
Form (BPI-SF) worst pain in last 24 hours was considered asymptomatic, and a score of 2-3 was 
considered mildly symptomatic.

In study 302, (n = 1,088) the median age of enrolled patients was 71 years for patients treated with 
ZYTIGA plus prednisone or prednisolone and 70 years for patients treated with placebo plus 
prednisone or prednisolone. The number of patients treated with ZYTIGA by racial group was 
Caucasian 520 (95.4%), Black 15 (2.8%), Asian 4 (0.7%) and other 6 (1.1%). The Eastern Cooperative 
Oncology Group (ECOG) performance status was 0 for 76% of patients, and 1 for 24% of patients in 
both arms. Fifty percent of patients had only bone metastases, an additional 31% of patients had bone 
and soft tissue or lymph node metastases and 19% of patients had only soft tissue or lymph node 
metastases. Patients with visceral metastases were excluded. Co-primary efficacy endpoints were 
overall survival and radiographic progression-free survival (rPFS). In addition to the co-primary 
endpoint measures, benefit was also assessed using time to opiate use for cancer pain, time to initiation 
of cytotoxic chemotherapy, time to deterioration in ECOG performance score by ≥ 1 point and time to 
PSA progression based on Prostate Cancer Working Group-2 (PCWG2) criteria. Study treatments 
were discontinued at the time of unequivocal clinical progression. Treatments could also be 
discontinued at the time of confirmed radiographic progression at the discretion of the investigator.

Radiographic progression free survival (rPFS) was assessed with the use of sequential imaging studies 
as defined by PCWG2 criteria (for bone lesions) and modified Response Evaluation Criteria In Solid 



37

Tumors (RECIST) criteria (for soft tissue lesions). Analysis of rPFS utilised centrally-reviewed 
radiographic assessment of progression.

At the planned rPFS analysis there were 401 events, 150 (28%) of patients treated with ZYTIGA and 
251 (46%) of patients treated with placebo had radiographic evidence of progression or had died. A 
significant difference in rPFS between treatment groups was observed (see Table 4 and Figure 3).

Table 4: Study 302: Radiographic progression-free survival of patients treated with either 
ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH 
analogues or prior orchiectomy

ZYTIGA
(N = 546)

Placebo
(N = 542)

Radiographic 
Progression-free Survival 

(rPFS)
Progression or death 150 (28%) 251 (46%)

Median rPFS in months
(95% CI)

Not reached
(11.66; NE)

8.3
(8.12; 8.54)

p-value* < 0.0001
Hazard ratio** (95% CI) 0.425 (0.347; 0.522)

NE = Not estimated
* p-value is derived from a log-rank test stratified by baseline ECOG score (0 or 1)
** Hazard ratio < 1 favours ZYTIGA

Figure 3: Kaplan Meier curves of radiographic progression-free survival in patients treated 
with either ZYTIGA or placebo in combination with prednisone or prednisolone 
plus LHRH analogues or prior orchiectomy

AA = ZYTIGA

However, subject data continued to be collected through the date of the second interim analysis of 
Overall survival (OS). The investigator radiographic review of rPFS performed as a follow up 
sensitivity analysis is presented in Table 5 and Figure 4.

Six hundred and seven (607) subjects had radiographic progression or died: 271 (50%) in the 
abiraterone acetate group and 336 (62%) in the placebo group. Treatment with abiraterone acetate 



38

decreased the risk of radiographic progression or death by 47% compared with placebo 
(HR = 0.530; 95% CI: [0.451; 0.623], p < 0.0001). The median rPFS was 16.5 months in the 
abiraterone acetate group and 8.3 months in the placebo group.

Table 5: Study 302: Radiographic progression-free survival of patients treated with either 
ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH 
analogues or prior orchiectomy (At second interim analysis of OS-Investigator 
Review)

ZYTIGA
(N = 546)

Placebo
(N = 542)

Radiographic 
Progression-free Survival 

(rPFS)
Progression or death 271 (50%) 336 (62%)

Median rPFS in months
(95% CI)

16.5
(13.80; 16.79)

8.3
(8.05; 9.43)

p-value* < 0.0001
Hazard ratio**

(95% CI)
0.530 (0.451; 0.623)

* p-value is derived from a log-rank test stratified by baseline ECOG score (0 or 1)
** Hazard ratio < 1 favours ZYTIGA

Figure 4: Kaplan Meier curves of radiographic progression-free survival in patients treated 
with either ZYTIGA or placebo in combination with prednisone or prednisolone 
plus LHRH analogues or prior orchiectomy (At second interim analysis of 
OS-Investigator Review)

AA = ZYTIGA

A planned interim analysis (IA) for OS was conducted after 333 deaths were observed. The study was 
unblinded based on the magnitude of clinical benefit observed and patients in the placebo group were 
offered treatment with ZYTIGA. Overall survival was longer for ZYTIGA than placebo with a 25%
reduction in risk of death (HR = 0.752; 95% CI: [0.606; 0.934], p = 0.0097), but OS was not mature 



39

and interim results did not meet the pre-specified stopping boundary for statistical significance (see 
Table 4). Survival continued to be followed after this IA.

The planned final analysis for OS was conducted after 741 deaths were observed (median follow up of 
49 months). Sixty-five percent (354 of 546) of patients treated with ZYTIGA, compared with 71% 
(387 of 542) of patients treated with placebo, had died. A statistically significant OS benefit in favour 
of the ZYTIGA-treated group was demonstrated with a 19.4% reduction in risk of death 
(HR = 0.806; 95% CI: [0.697; 0.931], p = 0.0033) and an improvement in median OS of 4.4 months 
(ZYTIGA 34.7 months, placebo 30.3 months) (see Table 6 and Figure 5). This improvement was 
demonstrated even though 44% of patients in the placebo arm received ZYTIGA as subsequent 
therapy.

Table 6: Study 302: Overall survival of patients treated with either ZYTIGA or placebo in
combination with prednisone or prednisolone plus LHRH analogues or prior 
orchiectomy

ZYTIGA
(N = 546)

Placebo
(N = 542)

Interim survival analysis
Deaths (%) 147 (27%) 186 (34%)

Median survival (months)
(95% CI)

Not reached
(NE; NE)

27.2
(25.95; NE)

p-value* 0.0097
Hazard ratio** (95% CI) 0.752 (0.606; 0.934)
Final survival analysis

Deaths 354 (65%) 387 (71%)
Median overall survival in 

months (95% CI)
34.7 (32.7; 36.8) 30.3 (28.7; 33.3)

p-value* 0.0033
Hazard ratio** (95% CI) 0.806 (0.697; 0.931)

NE = Not Estimated
* p-value is derived from a log-rank test stratified by baseline ECOG score (0 or 1)
** Hazard ratio < 1 favours ZYTIGA



40

Figure 5: Kaplan Meier survival curves of patients treated with either ZYTIGA or placebo in 
combination with prednisone or prednisolone plus LHRH analogues or prior 
orchiectomy, final analysis

AA = ZYTIGA

In addition to the observed improvements in overall survival and rPFS, benefit was demonstrated for 
ZYTIGA vs. placebo treatment in all secondary endpoint measures as follows:

Time to PSA progression based on PCWG2 criteria: The median time to PSA progression was 
11.1 months for patients receiving ZYTIGA and 5.6 months for patients receiving placebo 
(HR = 0.488; 95% CI: [0.420; 0.568], p < 0.0001). The time to PSA progression was approximately 
doubled with ZYTIGA treatment (HR = 0.488). The proportion of subjects with a confirmed PSA 
response was greater in the ZYTIGA group than in the placebo group (62% vs. 24%; p < 0.0001). In 
subjects with measurable soft tissue disease, significantly increased numbers of complete and partial 
tumor responses were seen with ZYTIGA treatment.

Time to opiate use for cancer pain: The median time to opiate use for prostate cancer pain at the time 
of final analysis was 33.4 months for patients receiving ZYTIGA and was 23.4 months for patients 
receiving placebo (HR = 0.721; 95% CI: [0.614; 0.846], p < 0.0001).

Time to initiation of cytotoxic chemotherapy: The median time to initiation of cytotoxic chemotherapy 
was 25.2 months for patients receiving ZYTIGA and 16.8 months for patients receiving placebo 
(HR = 0.580; 95% CI: [0.487; 0.691], p < 0.0001).

Time to deterioration in ECOG performance score by ≥ 1 point: The median time to deterioration in 
ECOG performance score by ≥ 1 point was 12.3 months for patients receiving ZYTIGA and 
10.9 months for patients receiving placebo (HR = 0.821; 95% CI: [0.714; 0.943], p = 0.0053).

The following study endpoints demonstrated a statistically significant advantage in favour of ZYTIGA 
treatment:



41

Objective response: Objective response was defined as the proportion of subjects with measurable 
disease achieving a complete or partial response according to RECIST criteria (baseline lymph node 
size was required to be ≥ 2 cm to be considered a target lesion). The proportion of subjects with 
measurable disease at baseline who had an objective response was 36% in the ZYTIGA group and 
16% in the placebo group (p < 0.0001).

Pain: Treatment with ZYTIGA significantly reduced the risk of average pain intensity progression by 
18% compared with placebo (p = 0.0490). The median time to progression was 26.7 months in the 
ZYTIGA group and 18.4 months in the placebo group.

Time to degradation in the FACT-P (Total Score): Treatment with ZYTIGA decreased the risk of 
FACT-P (Total Score) degradation by 22% compared with placebo (p = 0.0028). The median time to 
degradation in FACT-P (Total Score) was 12.7 months in the ZYTIGA group and 8.3 months in the 
placebo group.

Study 301 (patients who had received prior chemotherapy)
Study 301 enrolled patients who had received prior docetaxel. Patients were not required to show 
disease progression on docetaxel, as toxicity from this chemotherapy may have led to discontinuation.
Patients were maintained on study treatments until there was PSA progression (confirmed 25% 
increase over the patient’s baseline/nadir) together with protocol-defined radiographic progression and 
symptomatic or clinical progression. Patients with prior ketoconazole treatment for prostate cancer 
were excluded from this study. The primary efficacy endpoint was overall survival.

The median age of enrolled patients was 69 years (range 39-95). The number of patients treated with 
ZYTIGA by racial group was Caucasian 737 (93.2%), Black 28 (3.5%), Asian 11 (1.4%) and other 14 
(1.8%). Eleven percent of patients enrolled had an ECOG performance score of 2; 70% had 
radiographic evidence of disease progression with or without PSA progression; 70% had received one 
prior cytotoxic chemotherapy and 30% received two. Liver metastasis was present in 11% of patients 
treated with ZYTIGA.

In a planned analysis conducted after 552 deaths were observed, 42% (333 of 797) of patients treated 
with ZYTIGA compared with 55% (219 of 398) of patients treated with placebo, had died. A 
statistically significant improvement in median overall survival was seen in patients treated with 
ZYTIGA (see Table 7).

Table 7: Overall survival of patients treated with either ZYTIGA or placebo in 
combination with prednisone or prednisolone plus LHRH analogues or prior 
orchiectomy

ZYTIGA
(N = 797)

Placebo
(N = 398)

Primary Survival Analysis
Deaths (%) 333 (42%) 219 (55%)

Median survival (months)
(95% CI)

14.8 (14.1; 15.4) 10.9 (10.2; 12.0)

p-valuea < 0.0001
Hazard ratio (95% CI)b 0.646 (0.543; 0.768)

Updated Survival Analysis
Deaths (%) 501 (63%) 274 (69%)

Median survival (months)
(95% CI)

15.8 (14.8; 17.0) 11.2 (10.4; 13.1)

Hazard ratio (95% CI)b 0.740 (0.638; 0.859)
a p-value is derived from a log-rank test stratified by ECOG performance status score (0-1 vs. 2), pain score (absent vs. 

present), number of prior chemotherapy regimens (1 vs. 2), and type of disease progression (PSA only vs. 
radiographic).

b Hazard ratio is derived from a stratified proportional hazards model. Hazard ratio < 1 favours ZYTIGA



42

At all evaluation time points after the initial few months of treatment, a higher proportion of patients 
treated with ZYTIGA remained alive, compared with the proportion of patients treated with placebo
(see Figure 6).

Figure 6: Kaplan Meier survival curves of patients treated with either ZYTIGA or placebo in 
combination with prednisone or prednisolone plus LHRH analogues or prior 
orchiectomy

AA = ZYTIGA



43

Subgroup survival analyses showed a consistent survival benefit for treatment with ZYTIGA (see 
Figure 7).

Figure 7: Overall survival by subgroup: hazard ratio and 95% confidence interval

AA = ZYTIGA; BPI = Brief Pain Inventory; C.I. = confidence interval; ECOG = Eastern Cooperative Oncology Group 
performance score; HR = hazard ratio; NE = not evaluable

In addition to the observed improvement in overall survival, all secondary study endpoints favoured 
ZYTIGA and were statistically significant after adjusting for multiple testing as follows:

Patients receiving ZYTIGA demonstrated a significantly higher total PSA response rate (defined as a 
≥ 50% reduction from baseline), compared with patients receiving placebo, 38% vs. 10%, p < 0.0001.

The median time to PSA progression was 10.2 months for patients treated with ZYTIGA and 
6.6 months for patients treated with placebo (HR = 0.580; 95% CI: [0.462; 0.728], p < 0.0001).

The median radiographic progression-free survival was 5.6 months for patients treated with ZYTIGA 
and 3.6 months for patients who received placebo (HR = 0.673; 95% CI: [0.585; 0.776], p < 0.0001).

Pain
The proportion of patients with pain palliation was statistically significantly higher in the ZYTIGA 
group than in the placebo group (44% vs. 27%, p = 0.0002). A responder for pain palliation was 
defined as a patient who experienced at least a 30% reduction from baseline in the BPI-SF worst pain 
intensity score over the last 24 hours without any increase in analgesic usage score observed at 
two consecutive evaluations four weeks apart. Only patients with a baseline pain score of ≥ 4 and at 
least one post-baseline pain score were analysed (N = 512) for pain palliation.

A lower proportion of patients treated with ZYTIGA had pain progression compared to patients taking 
placebo at 6 (22% vs. 28%), 12 (30% vs. 38%) and 18 months (35% vs. 46%). Pain progression was 
defined as an increase from baseline of ≥ 30% in the BPI-SF worst pain intensity score over the 
previous 24 hours without a decrease in analgesic usage score observed at two consecutive visits, or an 
increase of ≥ 30% in analgesic usage score observed at two consecutive visits. The time to pain 
progression at the 25th percentile was 7.4 months in the ZYTIGA group, versus 4.7 months in the 
placebo group.



44

Skeletal-related events
A lower proportion of patients in the ZYTIGA group had skeletal-related events compared with the 
placebo group at 6 months (18% vs. 28%), 12 months (30% vs. 40%), and 18 months (35% vs. 40%). 
The time to first skeletal-related event at the 25th percentile in the ZYTIGA group was twice that of the 
control group at 9.9 months versus 4.9 months. A skeletal-related event was defined as a pathological 
fracture, spinal cord compression, palliative radiation to bone, or surgery to bone.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with 
ZYTIGA in all subsets of the paediatric population in advanced prostate cancer. See section 4.2 for 
information on paediatric use.

5.2 Pharmacokinetic properties

Following administration of abiraterone acetate, the pharmacokinetics of abiraterone and abiraterone 
acetate have been studied in healthy subjects, patients with metastatic advanced prostate cancer and 
subjects without cancer with hepatic or renal impairment. Abiraterone acetate is rapidly converted in 
vivo to abiraterone, an androgen biosynthesis inhibitor (see section 5.1).

Absorption
Following oral administration of abiraterone acetate in the fasting state, the time to reach maximum 
plasma abiraterone concentration is approximately 2 hours.

Administration of abiraterone acetate with food, compared with administration in a fasted state, results 
in up to a 10-fold (AUC) and up to a 17-fold (Cmax) increase in mean systemic exposure of abiraterone, 
depending on the fat content of the meal. Given the normal variation in the content and composition of 
meals, taking ZYTIGA with meals has the potential to result in highly variable exposures. Therefore, 
ZYTIGA must not be taken with food. It should be taken at least one hour before or at least two hours 
after eating. The tablets should be swallowed whole with water (see section 4.2).

Distribution
The plasma protein binding of 14C-abiraterone in human plasma is 99.8%. The apparent volume of 
distribution is approximately 5,630 l, suggesting that abiraterone extensively distributes to peripheral 
tissues.

Biotransformation
Following oral administration of 14C-abiraterone acetate as capsules, abiraterone acetate is hydrolysed 
to abiraterone, which then undergoes metabolism including sulphation, hydroxylation and oxidation 
primarily in the liver. The majority of circulating radioactivity (approximately 92%) is found in the 
form of metabolites of abiraterone. Of 15 detectable metabolites, 2 main metabolites, abiraterone 
sulphate and N-oxide abiraterone sulphate, each represents approximately 43% of total radioactivity.

Elimination
The mean half-life of abiraterone in plasma is approximately 15 hours based on data from healthy 
subjects. Following oral administration of 14C-abiraterone acetate 1,000 mg, approximately 88% of the 
radioactive dose is recovered in faeces and approximately 5% in urine. The major compounds present 
in faeces are unchanged abiraterone acetate and abiraterone (approximately 55% and 22% of the 
administered dose, respectively).

Hepatic impairment
The pharmacokinetics of abiraterone acetate was examined in subjects with pre-existing mild or 
moderate hepatic impairment (Child-Pugh Class A and B, respectively) and in healthy control 
subjects. Systemic exposure to abiraterone after a single oral 1,000 mg dose increased by 
approximately 11% and 260% in subjects with mild and moderate pre-existing hepatic impairment, 
respectively. The mean half-life of abiraterone is prolonged to approximately 18 hours in subjects with 
mild hepatic impairment and to approximately 19 hours in subjects with moderate hepatic impairment.



45

In another trial, the pharmacokinetics of abiraterone were examined in subjects with pre-existing 
severe (n = 8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal 
hepatic function. The AUC to abiraterone increased by approximately 600% and the fraction of free 
drug increased by 80% in subjects with severe hepatic impairment compared to subjects with normal 
hepatic function.

No dose adjustment is necessary for patients with pre-existing mild hepatic impairment.
The use of abiraterone acetate 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 4.4). 
abiraterone acetate should not be used in patients with severe hepatic impairment (see sections 4.2, 4.3 
and 4.4).

For patients who develop hepatotoxicity during treatment, suspension of treatment and dose 
adjustment may be required (see sections 4.2 and 4.4).

Renal impairment
The pharmacokinetics of abiraterone acetate was compared in patients with end-stage renal disease on 
a stable haemodialysis schedule versus matched control subjects with normal renal function. Systemic 
exposure to abiraterone after a single oral 1,000 mg dose did not increase in subjects with end-stage 
renal disease on dialysis. Administration in patients with renal impairment, including severe renal 
impairment, does not require dose reduction (see section 4.2). However, there is no clinical experience 
in patients with prostate cancer and severe renal impairment. Caution is advised in these patients.

5.3 Preclinical safety data

In all animal toxicity studies, circulating testosterone levels were significantly reduced. As a result, 
reduction in organ weights and morphological and/or histopathological changes in the reproductive 
organs, and the adrenal, pituitary and mammary glands were observed. All changes showed complete 
or partial reversibility. The changes in the reproductive organs and androgen-sensitive organs are 
consistent with the pharmacology of abiraterone. All treatment-related hormonal changes reversed or 
were shown to be resolving after a 4-week recovery period.

In fertility studies in both male and female rats, abiraterone acetate reduced fertility, which was 
completely reversible in 4 to 16 weeks after abiraterone acetate was stopped.

In a developmental toxicity study in the rat, abiraterone acetate affected pregnancy including reduced 
foetal weight and survival. Effects on the external genitalia were observed though abiraterone acetate 
was not teratogenic.

In these fertility and developmental toxicity studies performed in the rat, all effects were related to the 
pharmacological activity of abiraterone.

Aside from reproductive organ changes seen in all animal toxicology studies, non-clinical data reveal 
no special hazard for humans based on conventional studies of safety pharmacology, repeated dose 
toxicity, genotoxicity and carcinogenic potential. Abiraterone acetate was not carcinogenic in a 
6-month study in the transgenic (Tg.rasH2) mouse. In a 24-month carcinogenicity study in the rat, 
abiraterone acetate increased the incidence of interstitial cell neoplasms in the testes. This finding is 
considered related to the pharmacological action of abiraterone and rat specific. Abiraterone acetate 
was not carcinogenic in female rats.

The active substance, abiraterone, shows an environmental risk for the aquatic environment, especially 
to fish.



46

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core
Microcrystalline cellulose (silicified)
Croscarmellose sodium
Hypromellose 2910 (15 mPa.S)
Lactose monohydrate
Magnesium stearate
Colloidal anhydrous silica
Sodium laurilsulfate

Film-coat
Iron oxide black (E172)
Iron oxide red (E172)
Macrogol 3350
Polyvinyl alcohol
Talc
Titanium dioxide

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVdC/PE/PVC/aluminum blister of 14 film-coated tablets in a cardboard wallet. Each carton contains 
(56 film-coated tablets) 4 wallets.
PVdC/PE/PVC/aluminum blister of 12 film-coated tablets in a cardboard wallet. Each carton contains 
(60 film-coated tablets) 5 wallets.

6.6 Special precautions for disposal

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).

7. MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/714/002 - 56 film-coated tablets (4 wallet packs of 14)



47

EU/1/11/714/003 - 60 film-coated tablets (5 wallet packs of 12)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 05 September 2011

Date of latest renewal: 26 May 2016

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

http://www.ema.europa.eu/


48

ANNEX II

A. MANUFACTURER OF THE BIOLOGIVAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT



49

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Janssen-Cilag SpA
Via C. Janssen
IT-04100 Borgo San Michele
Latina
Italy

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any
subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation
and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.



50

ANNEX III

LABELLING AND PACKAGE LEAFLET



51

A. LABELLING



52

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON 250 mg

1. NAME OF THE MEDICINAL PRODUCT

ZYTIGA 250 mg tablets
abiraterone acetate

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 250 mg abiraterone acetate.

3. LIST OF EXCIPIENTS

Contains lactose and sodium.
See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

120 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Take ZYTIGA at least one hour before or at least two hours after eating.
Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Women who are or may be pregnant should not handle ZYTIGA without gloves.

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



53

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Discard unused contents appropriately in accordance with local requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/714/001

13. BATCH NUMBER

BN

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

ZYTIGA 250 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



54

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING

BOTTLE LABEL 250 mg

1. NAME OF THE MEDICINAL PRODUCT

ZYTIGA 250 mg tablets
abiraterone acetate

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 250 mg abiraterone acetate.

3. LIST OF EXCIPIENTS

Contains lactose and sodium.
See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

120 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Take ZYTIGA at least one hour before or at least two hours after eating.
Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Women who are or may be pregnant should not handle ZYTIGA without gloves.

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



55

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Discard unused contents appropriately in accordance with local requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/714/001

13. BATCH NUMBER

BN

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE



56

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON 500 mg

1. NAME OF THE MEDICINAL PRODUCT

ZYTIGA 500 mg film-coated tablets
abiraterone acetate

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains 500 mg abiraterone acetate.

3. LIST OF EXCIPIENTS

Contains lactose and sodium.
See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

56 film-coated tablets
60 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Take ZYTIGA at least one hour before or at least two hours after eating.
Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



57

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Discard unused contents appropriately in accordance with local requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/714/002 (56 film-coated tablets)
EU/1/11/714/003 (60 film-coated tablets)

13. BATCH NUMBER

BN

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

ZYTIGA 500 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



58

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING

WALLET 500 mg (30 days)

1. NAME OF THE MEDICINAL PRODUCT

ZYTIGA 500 mg film-coated tablets
abiraterone acetate

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains 500 mg abiraterone acetate.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

12 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Fill in your weekdays

Start date:

Day

Read the package leaflet before use.
Take ZYTIGA at least one hour before or at least two hours after eating.
Swallow the tablets whole with water.
Do not break the tablets.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



59

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Discard unused contents appropriately in accordance with local requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/714/003

13. BATCH NUMBER

BN

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

ZYTIGA 500 mg



60

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING

WALLET 500 mg (28 days)

1. NAME OF THE MEDICINAL PRODUCT

ZYTIGA 500 mg film-coated tablets
abiraterone acetate

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains 500 mg abiraterone acetate.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

14 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Take ZYTIGA at least one hour before or at least two hours after eating.
Swallow the tablets whole with water.

Do not break the tablets.

Monday
Tuesday
Wednesday
Thursday
Friday
Saturday
Sunday

Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



61

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Discard unused contents appropriately in accordance with local requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/714/002

13. BATCH NUMBER

BN

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

ZYTIGA 500 mg



62

PARTICULARS TO APPEAR ON BLISTERS or STRIPS

BLISTER 500 mg

1. NAME OF THE MEDICINAL PRODUCT

ZYTIGA 500 mg film-coated tablets
abiraterone acetate

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV

3. EXPIRY DATE

EXP

4. BATCH NUMBER

BN

5. OTHER



63

B. PACKAGE LEAFLET



64

Package leaflet: Information for the user

ZYTIGA 250 mg tablets
abiraterone acetate

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet:
1. What ZYTIGA is and what it is used for
2. What you need to know before you take ZYTIGA
3. How to take ZYTIGA
4. Possible side effects
5. How to store ZYTIGA
6. Contents of the pack and other information

1. What ZYTIGA is and what it is used for

ZYTIGA contains a medicine called abiraterone acetate. It is used to treat prostate cancer in adult men 
that has spread to other parts of the body. ZYTIGA stops your body from making testosterone; this can 
slow the growth of prostate cancer.

When ZYTIGA is prescribed for the early stage of disease where it is still responding to hormone 
therapy, it is used with a treatment that lowers testosterone (androgen deprivation therapy). 

When you take this medicine your doctor will also prescribe another medicine called prednisone or 
prednisolone. This is to lower your chances of getting high blood pressure, having too much water in 
your body (fluid retention), or having reduced levels of a chemical known as potassium in your blood.

2. What you need to know before you take ZYTIGA

Do not take ZYTIGA
- if you are allergic to abiraterone acetate or any of the other ingredients of this medicine (listed 

in section 6).
- if you are a woman, especially if pregnant. ZYTIGA is for use in male patients only.
- if you have severe liver damage.
- in combination with Ra-223 (which is used to treat prostate cancer).

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before taking this medicine.

Warnings and precautions
Talk to your doctor or pharmacist before taking this medicine:
- if you have liver problems
- if you have been told you have high blood pressure or heart failure or low blood potassium (low 

blood potassium may increase the risk of heart rhythm problems)
- if you have had other heart or blood vessel problems
- if you have an irregular or rapid heart rate
- if you have shortness of breath



65

- if you have gained weight rapidly
- if you have swelling in the feet, ankles, or legs
- if you have taken a medicine known as ketoconazole in the past for prostate cancer
- about the need to take this medicine with prednisone or prednisolone
- about possible effects on your bones
- if you have high blood sugar.

Tell your doctor if you have been told you have any heart or blood vessel conditions, including heart 
rhythm problems (arrhythmia), or are being treated with medicines for these conditions.

Tell your doctor if you have yellowing of the skin or eyes, darkening of the urine, or severe nausea or 
vomiting, as these could be signs or symptoms of liver problems. Rarely, failure of the liver to 
function (called acute liver failure) may occur, which can lead to death.

Decrease in red blood cells, reduced sex drive (libido), muscle weakness and/or muscle pain may
occur.

ZYTIGA must not be given in combination with Ra-223 due to a possible increase in the risk of bone 
fracture or death. 

If you plan to take Ra-223 following treatment with ZYTIGA and prednisone/prednisolone, you must
wait 5 days before starting treatment with Ra-223.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking this 
medicine.

Blood monitoring
ZYTIGA may affect your liver, and you may not have any symptoms. When you are taking this 
medicine, your doctor will check your blood periodically to look for any effects on your liver.

Children and adolescents
This medicine is not for use in children and adolescents. If ZYTIGA is accidentally ingested by a child 
or adolescent, go to the hospital immediately and take the package leaflet with you to show to the 
emergency doctor.

Other medicines and ZYTIGA
Ask your doctor or pharmacist for advice before taking any medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This is important because ZYTIGA may increase the effects of a number of medicines 
including heart medicines, tranquilisers, some medicines for diabetes, herbal medicines (e.g., 
St John’s wort) and others. Your doctor may want to change the dose of these medicines. Also, some 
medicines may increase or decrease the effects of ZYTIGA. This may lead to side effects or to 
ZYTIGA not working as well as it should.

Androgen deprivation treatment may increase the risk of heart rhythm problems. Tell your doctor if 
you are receiving medicine
- used to treat heart rhythm problems (e.g. quinidine, procainamide, amiodarone and sotalol);
- known to increase the risk of heart rhythm problems [e.g. methadone (used for pain relief and 

part of drug addiction detoxification), moxifloxacin (an antibiotic), antipsychotics (used for 
serious mental illnesses)].

Tell your doctor if you are taking any of the medicines listed above.

ZYTIGA with food
- This medicine must not be taken with food (see section 3, “Taking this medicine”).
- Taking ZYTIGA with food may cause side effects.



66

Pregnancy and breast-feeding
ZYTIGA is not for use in women.
- This medicine may cause harm to the unborn child if it is taken by women who are 

pregnant.
- Women who are pregnant or who may be pregnant should wear gloves if they need to 

touch or handle ZYTIGA.
- If you are having sex with a woman who can become pregnant, use a condom and another 

effective birth control method.
- If you are having sex with a pregnant woman, use a condom to protect the unborn child.

Driving and using machines
This medicine is not likely to affect your being able to drive and use any tools or machines.

ZYTIGA contains lactose and sodium
- ZYTIGA contains lactose (a type of sugar). If you have been told by your doctor that you have 

an intolerance to some sugars, contact your doctor before taking this medicine.
- This medicine also contains approximately 27 mg of sodium in a four tablet daily dose. To be 

taken into consideration by patients on a controlled sodium diet.

3. How to take ZYTIGA

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.

How much to take
The recommended dose is 1,000 mg (four tablets) once a day.

Taking this medicine
- Take this medicine by mouth.
- Do not take ZYTIGA with food.
- Take ZYTIGA at least one hour before or at least two hours after eating (see section 2, 

“ZYTIGA with food”).
- Swallow the tablets whole with water.
- Do not break the tablets.
- ZYTIGA is taken with a medicine called prednisone or prednisolone. Take the prednisone or 

prednisolone exactly as your doctor has told you.
- You need to take prednisone or prednisolone every day while you are taking ZYTIGA.
- The amount of prednisone or prednisolone you take may need to change if you have a medical 

emergency. Your doctor will tell you if you need to change the amount of prednisone or 
prednisolone you take. Do not stop taking prednisone or prednisolone unless your doctor tells 
you to.

Your doctor may also prescribe other medicines while you are taking ZYTIGA and prednisone or 
prednisolone.

If you take more ZYTIGA than you should
If you take more than you should, talk to your doctor or go to a hospital immediately.

If you forget to take ZYTIGA
- If you forget to take ZYTIGA or prednisone or prednisolone, take your usual dose the following 

day.
- If you forget to take ZYTIGA or prednisone or prednisolone for more than one day, talk to your 

doctor without delay.



67

If you stop taking ZYTIGA
Do not stop taking ZYTIGA or prednisone or prednisolone unless your doctor tells you to.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking ZYTIGA and see a doctor immediately if you notice any of the following:
- Muscle weakness, muscle twitches or a pounding heart beat (palpitations). These may be signs 

that the level of potassium in your blood is low.

Other side effects include:
Very common (may affect more than 1 in 10 people):
Fluid in your legs or feet, low blood potassium, liver function test increases, high blood pressure, 
urinary tract infection, diarrhoea.
Common (may affect up to 1 in 10 people):
High fat levels in your blood, chest pain, irregular heart beat (atrial fibrillation), heart failure, rapid 
heart rate, severe infections called sepsis, bone fractures, indigestion, blood in urine, rash.
Uncommon (may affect up to 1 in 100 people):
Adrenal gland problems (related to salt and water problems), abnormal heart rhythm (arrhythmia), 
muscle weakness and/or muscle pain
Rare (may affect up to 1 in 1,000 people):
Lung irritation (also called allergic alveolitis).
Failure of the liver to function (also called acute liver failure).
Not known (frequency cannot be estimated from the available data):
Heart attack, changes in ECG - electrocardiogram (QT prolongation), and serious allergic reactions 
with difficulty swallowing or breathing, swollen face, lips, tongue or throat, or an itchy rash.

Bone loss may occur in men treated for prostate cancer. ZYTIGA in combination with prednisone or 
prednisolone may increase bone loss.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store ZYTIGA

- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the carton and the bottle label. 

The expiry date refers to the last day of that month.
- This medicinal product does not require any special storage conditions.
- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 

how to throw away medicines you no longer use. These measures will help to protect the 
environment.

6. Contents of the pack and other information

What ZYTIGA contains
- The active substance is abiraterone acetate. Each tablet contains 250 mg abiraterone acetate.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


68

- The other ingredients are microcrystalline cellulose, croscarmellose sodium, lactose 
monohydrate, magnesium stearate, povidone (K29/K32), colloidal anhydrous silica, and sodium 
laurilsulfate (see section 2, “ZYTIGA contains lactose and sodium”).

What ZYTIGA looks like and contents of the pack
- ZYTIGA tablets are white to off-white, oval shaped (15.9 mm long x 9.5 mm wide), with 

“AA250” written on one side.
- The tablets are provided in a plastic bottle with a child-resistant closure. Each bottle contains 

120 tablets. Each carton contains one bottle.

Marketing Authorisation Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen-Cilag SpA
Via C. Janssen
Borgo San Michele
I-04100 Latina, Italy

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Janssen-Cilag NV
janssen@jacbe.jnj.com
Tel/Tél: +32 14 64 94 11

Lietuva
UAB "JOHNSON & JOHNSON"
lt@its.jnj.com
Tel: +370 5 278 68 88

България
„Джонсън & Джонсън България” ЕООД
jjsafety@its.jnj.com
Тел.: +359 2 489 94 00

Luxembourg/Luxemburg
Janssen-Cilag NV
janssen@jacbe.jnj.com
Tel/Tél: +32 14 64 94 11

Česká republika
Janssen-Cilag s.r.o.
Tel. +420 227 012 227

Magyarország
Janssen-Cilag Kft.
janssenhu@its.jnj.com
Tel.: +36 1 884 2858

Danmark
Janssen-Cilag A/S
jacdk@its.jnj.com
Tlf: +45 45 94 82 82

Malta
AM MANGION LTD.
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
jancil@its.jnj.com
Tel: +49 2137 955 955

Nederland
Janssen-Cilag B.V.
janssen@jacnl.jnj.com
Tel: +31 76 711 1111

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
ee@its.jnj.com
Tel: +372 617 7410

Norge
Janssen-Cilag AS
jacno@its.jnj.com
Tlf: +47 24 12 65 00

mailto:janssenhu@its.jnj.com


69

Ελλάδα
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
contacto@its.jnj.com
Tel: +34 91 722 81 00

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.+48 22 237 60 00

France
Janssen-Cilag
medisource@its.jnj.com
Tél: 0 800 25 50 75 / +33 1 55 00 40 03

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
jjsafety@JNJCR.JNJ.com
Tel: +385 1 6610 700

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: +353 1 800 709 122

Slovenija
Johnson & Johnson d.o.o.
Janssen_safety_slo@its.jnj.com
Tel: +386 1 401 18 00

Ísland
Janssen-Cilag AB
c/o Vistor hf.
janssen@vistor.is
Sími: +354 535 7000

Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400

Italia
Janssen-Cilag SpA
janssenita@its.jnj.com
Tel: 800.688.777 / +39 02 2510 1

Suomi/Finland
Janssen-Cilag Oy
jacfi@its.jnj.com
Puh/Tel: +358 207 531 300

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
jacse@its.jnj.com
Tel: +46 8 626 50 00

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
lv@its.jnj.com
Tel: +371 678 93561

United Kingdom
Janssen-Cilag Ltd.
Tel: +44 1 494 567 444

This leaflet was last revised in

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.

http://www.ema.europa.eu/
mailto:contacto@its.jnj.com


70

Package leaflet: Information for the user

ZYTIGA 500 mg film-coated tablets
abiraterone acetate

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet:
1. What ZYTIGA is and what it is used for
2. What you need to know before you take ZYTIGA
3. How to take ZYTIGA
4. Possible side effects
5. How to store ZYTIGA
6. Contents of the pack and other information

1. What ZYTIGA is and what it is used for

ZYTIGA contains a medicine called abiraterone acetate. It is used to treat prostate cancer in adult men 
that has spread to other parts of the body. ZYTIGA stops your body from making testosterone; this can 
slow the growth of prostate cancer.

When ZYTIGA is prescribed for the early stage of disease where it is still responding to hormone 
therapy, it is used with a treatment that lowers testosterone (androgen deprivation therapy ).

When you take this medicine your doctor will also prescribe another medicine called prednisone or 
prednisolone. This is to lower your chances of getting high blood pressure, having too much water in 
your body (fluid retention), or having reduced levels of a chemical known as potassium in your blood.

2. What you need to know before you take ZYTIGA

Do not take ZYTIGA
- if you are allergic to abiraterone acetate or any of the other ingredients of this medicine (listed 

in section 6).
- if you are a woman, especially if pregnant. ZYTIGA is for use in male patients only.
- if you have severe liver damage.
- in combination with Ra-223 (which is used to treat prostate cancer).

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before taking this medicine.

Warnings and precautions
Talk to your doctor or pharmacist before taking this medicine:
- if you have liver problems
- if you have been told you have high blood pressure or heart failure or low blood potassium (low 

blood potassium may increase the risk of heart rhythm problems)
- if you have had other heart or blood vessel problems
- if you have an irregular or rapid heart rate



71

- if you have shortness of breath
- if you have gained weight rapidly
- if you have swelling in the feet, ankles, or legs
- if you have taken a medicine known as ketoconazole in the past for prostate cancer
- about the need to take this medicine with prednisone or prednisolone
- about possible effects on your bones
- if you have high blood sugar.

Tell your doctor if you have been told you have any heart or blood vessel conditions, including heart 
rhythm problems (arrhythmia), or are being treated with medicines for these conditions.

Tell your doctor if you have yellowing of the skin or eyes, darkening of the urine, or severe nausea or 
vomiting, as these could be signs or symptoms of liver problems. Rarely, failure of the liver to 
function (called acute liver failure) may occur, which can lead to death.

Decrease in red blood cells, reduced sex drive (libido), muscle weakness and/or muscle pain may 
occur.

ZYTIGA must not be given in combination with Ra-223 due to a possible increase in the risk of bone 
fracture or death. 

If you plan to take Ra-223 following treatment with ZYTIGA and prednisone/prednisolone, you must 
wait 5 days before starting treatment with Ra-223.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking this 
medicine.

Blood monitoring
ZYTIGA may affect your liver, and you may not have any symptoms. When you are taking this 
medicine, your doctor will check your blood periodically to look for any effects on your liver.

Children and adolescents
This medicine is not for use in children and adolescents. If ZYTIGA is accidentally ingested by a child 
or adolescent, go to the hospital immediately and take the package leaflet with you to show to the 
emergency doctor.

Other medicines and ZYTIGA
Ask your doctor or pharmacist for advice before taking any medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This is important because ZYTIGA may increase the effects of a number of medicines 
including heart medicines, tranquilisers, some medicines for diabetes, herbal medicines (e.g., 
St John’s wort) and others. Your doctor may want to change the dose of these medicines. Also, some 
medicines may increase or decrease the effects of ZYTIGA. This may lead to side effects or to 
ZYTIGA not working as well as it should.

Androgen deprivation treatment may increase the risk of heart rhythm problems. Tell your doctor if 
you are receiving medicine
- used to treat heart rhythm problems (e.g. quinidine, procainamide, amiodarone and sotalol);
- known to increase the risk of heart rhythm problems [e.g. methadone (used for pain relief and 

part of drug addiction detoxification), moxifloxacin (an antibiotic), antipsychotics (used for 
serious mental illnesses)].

Tell your doctor if you are taking any of the medicines listed above.

ZYTIGA with food
- This medicine must not be taken with food (see section 3, “Taking this medicine”).



72

- Taking ZYTIGA with food may cause side effects.

Pregnancy and breast-feeding
ZYTIGA is not for use in women.
- This medicine may cause harm to the unborn child if it is taken by women who are 

pregnant.
- If you are having sex with a woman who can become pregnant, use a condom and another 

effective birth control method.
- If you are having sex with a pregnant woman, use a condom to protect the unborn child.

Driving and using machines
This medicine is not likely to affect your being able to drive and use any tools or machines.

ZYTIGA contains lactose and sodium
- ZYTIGA contains lactose (a type of sugar). If you have been told by your doctor that you have 

an intolerance to some sugars, contact your doctor before taking this medicine.
- This medicine also contains approximately 27 mg of sodium in a two tablet daily dose. To be 

taken into consideration by patients on a controlled sodium diet.

3. How to take ZYTIGA

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.

How much to take
The recommended dose is 1,000 mg (two tablets) once a day.

Taking this medicine
- Take this medicine by mouth.
- Do not take ZYTIGA with food.
- Take ZYTIGA at least one hour before or at least two hours after eating (see section 2, 

“ZYTIGA with food”).
- Swallow the tablets whole with water.
- Do not break the tablets.
- ZYTIGA is taken with a medicine called prednisone or prednisolone. Take the prednisone or 

prednisolone exactly as your doctor has told you.
- You need to take prednisone or prednisolone every day while you are taking ZYTIGA.
- The amount of prednisone or prednisolone you take may need to change if you have a medical 

emergency. Your doctor will tell you if you need to change the amount of prednisone or 
prednisolone you take. Do not stop taking prednisone or prednisolone unless your doctor tells 
you to.

Your doctor may also prescribe other medicines while you are taking ZYTIGA and prednisone or 
prednisolone.

If you take more ZYTIGA than you should
If you take more than you should, talk to your doctor or go to a hospital immediately.

If you forget to take ZYTIGA
- If you forget to take ZYTIGA or prednisone or prednisolone, take your usual dose the following 

day.
- If you forget to take ZYTIGA or prednisone or prednisolone for more than one day, talk to your 

doctor without delay.

If you stop taking ZYTIGA
Do not stop taking ZYTIGA or prednisone or prednisolone unless your doctor tells you to.



73

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking ZYTIGA and see a doctor immediately if you notice any of the following:
- Muscle weakness, muscle twitches or a pounding heart beat (palpitations). These may be signs 

that the level of potassium in your blood is low.

Other side effects include:
Very common (may affect more than 1 in 10 people):
Fluid in your legs or feet, low blood potassium, liver function test increases, high blood pressure, 
urinary tract infection, diarrhoea.
Common (may affect up to 1 in 10 people):
High fat levels in your blood, chest pain, irregular heart beat (atrial fibrillation), heart failure, rapid 
heart rate, severe infections called sepsis, bone fractures, indigestion, blood in urine, rash.
Uncommon (may affect up to 1 in 100 people):
Adrenal gland problems (related to salt and water problems), abnormal heart rhythm (arrhythmia), 
muscle weakness and/or muscle pain
Rare (may affect up to 1 in 1,000 people):
Lung irritation (also called allergic alveolitis).
Failure of the liver to function (also called acute liver failure).
Not known (frequency cannot be estimated from the available data):
Heart attack, changes in ECG - electrocardiogram (QT prolongation), and serious allergic reactions 
with difficulty swallowing or breathing, swollen face, lips, tongue or throat, or an itchy rash.

Bone loss may occur in men treated for prostate cancer. ZYTIGA in combination with prednisone or 
prednisolone may increase bone loss.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store ZYTIGA

- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the carton, cardboard wallet, 

and the blister. The expiry date refers to the last day of that month.
- This medicinal product does not require any special storage conditions.
- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 

how to throw away medicines you no longer use. These measures will help to protect the 
environment.

6. Contents of the pack and other information

What ZYTIGA contains
- The active substance is abiraterone acetate. Each film-coated tablet contains 500 mg abiraterone 

acetate.
- The other ingredients are microcrystalline cellulose (silicified); croscarmellose sodium; 

hypromellose 2910 (15 mPa.S); lactose monohydrate; magnesium stearate; colloidal anhydrous

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


74

silica; and sodium laurilsulfate (see section 2, “ZYTIGA contains lactose and sodium”) The 
film-coating contains iron oxide black (E172); iron oxide red (E172); macrogol 3350; polyvinyl 
alcohol; talc; and titanium dioxide.

What ZYTIGA looks like and contents of the pack
- ZYTIGA tablets are purple, oval-shaped, film-coated (20 mm long by 10 mm wide) with “AA” 

written on one side and “500” on the other side.
Each 28 day carton contains 56 film-coated tablets in 4 cardboard wallets of 14 film-coated 
tablets each.
Each 30 day carton contains 60 film-coated tablets in 5 cardboard wallets of 12 film-coated 
tablets each.

Marketing Authorisation Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen-Cilag SpA
Via C. Janssen
Borgo San Michele
I-04100 Latina, Italy

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Janssen-Cilag NV
janssen@jacbe.jnj.com
Tel/Tél: +32 14 64 94 11

Lietuva
UAB "JOHNSON & JOHNSON"
lt@its.jnj.com
Tel: +370 5 278 68 88

България
„Джонсън & Джонсън България” ЕООД
jjsafety@its.jnj.com
Тел.: +359 2 489 94 00

Luxembourg/Luxemburg
Janssen-Cilag NV
janssen@jacbe.jnj.com
Tel/Tél: +32 14 64 94 11

Česká republika
Janssen-Cilag s.r.o.
Tel. +420 227 012 227

Magyarország
Janssen-Cilag Kft.
janssenhu@its.jnj.com
Tel.: +36 1 884 2858

Danmark
Janssen-Cilag A/S
jacdk@its.jnj.com
Tlf: +45 45 94 82 82

Malta
AM MANGION LTD.
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
jancil@its.jnj.com
Tel: +49 2137 955 955

Nederland
Janssen-Cilag B.V.
janssen@jacnl.jnj.com
Tel: +31 76 711 1111

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
ee@its.jnj.com
Tel: +372 617 7410

Norge
Janssen-Cilag AS
jacno@its.jnj.com
Tlf: +47 24 12 65 00

mailto:janssenhu@its.jnj.com


75

Ελλάδα
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
contacto@its.jnj.com
Tel: +34 91 722 81 00

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.+48 22 237 60 00

France
Janssen-Cilag
medisource@its.jnj.com
Tél: 0 800 25 50 75 / +33 1 55 00 40 03

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
jjsafety@JNJCR.JNJ.com
Tel: +385 1 6610 700

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: +353 1 800 709 122

Slovenija
Johnson & Johnson d.o.o.
Janssen_safety_slo@its.jnj.com
Tel: +386 1 401 18 00

Ísland
Janssen-Cilag AB
c/o Vistor hf.
janssen@vistor.is
Sími: +354 535 7000

Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400

Italia
Janssen-Cilag SpA
janssenita@its.jnj.com
Tel: 800.688.777 / +39 02 2510 1

Suomi/Finland
Janssen-Cilag Oy
jacfi@its.jnj.com
Puh/Tel: +358 207 531 300

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
jacse@its.jnj.com
Tel: +46 8 626 50 00

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
lv@its.jnj.com
Tel: +371 678 93561

United Kingdom
Janssen-Cilag Ltd.
Tel: +44 1 494 567 444

This leaflet was last revised in

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.

http://www.ema.europa.eu/
mailto:contacto@its.jnj.com

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET