tine, phenobarbital) on the pharmacokinetics of abiraterone have not been eva luated, in vivo. Strong inhibitors and inducers of CYP3A4 during treatment are to be avoided, or used with caution.
4.6 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. Maternal use of a CYP17 inhibitor is expected to produce changes in hormone levels that could affect development of the foetus (see section 5.3).
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.
Pregnancy
ZYTIGA is not for use in women. Abiraterone acetate 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. It is not known if either abiraterone acetate or its metabolites are excreted in human milk.
Fertility
Reproductive toxicology studies were not conducted with abiraterone acetate. No fertility data are available.
4.7 Effects on ability to drive and use machines
ZYTIGA has no or negligible influence on the ability to drive or use machines.
4.8 Undesirable effects
Summary of the safety profile
The most common adverse reactions seen are peripheral oedema, hypokalaemia, hypertension and urinary tract infection.
ZYTIGA may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic consequence of its mechanism of action. In a phase 3 study, anticipated mineralocorticoid adverse reactions were seen more commonly in patients treated with ZYTIGA than in patients treated with placebo: hypokalaemia 17% versus 8%, hypertension 9% versus 7% and fluid retention (peripheral oedema) 25% versus 17%, respectively. In patients treated with ZYTIGA, CTCAE (version 3.0) Grades 3 and 4 hypokalaemia and CTCAE (version 3.0) Grades 3 and 4 hypertension were observed in 4% and 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 summary of adverse reactions
In studies of patients with metastatic advanced prostate cancer who were using a luteinising hormone-releasing hormone (LHRH) agonist, or were previously treated with orchiectomy, ZYTIGA was administered at a dose of 1,000 mg daily in combination with low dose prednisone or prednisolone (10 mg daily). Patients were intolerant to or had failed up to two prior chemotherapy regimens, one of which contained a taxane.
Adverse reactions observed during clinical studies 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).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 1: Adverse reactions identified in clinical studies
Infections and infestations
very common: urinary tract infection
Endocrine disorders
uncommon: adrenal insufficiency
Metabolism and nutrition disorders
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