T rises above 5 times the upper limit of normal, 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 20 times the upper limit of normal) 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.
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Caution is advised and monitoring for adrenocortical insufficiency should occur if patients are withdrawn from prednisone or prednisolone. If ZYTIGA is continued after corticosteroids are withdrawn, patients should be monitored for symptoms of mineralocorticoid excess (see information above).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 (castration resistant 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.
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.
4.5 Interaction with other medicinal products and other forms of interaction
Administration with food significantly increases the absorption of abiraterone acetate. The efficacy and safety of ZYTIGA given with food have not been established. ZYTIGA must not be taken with food (see sections 4.2 and 5.2).
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 ZYTIGA is administered 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, flecanide, codeine, oxycodone and tramadol (the latter three products requiring CYP2D6 to form their active analgesic metabolites).
Based on in vitro data, ZYTIGA is a substrate of CYP3A4. The effects of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or inducers (e.g., phenytoin, carbamazepine, rifampicin, rifabutin, rifapen |
