Posology : מינונים

5 DOSAGE AND ADMINISTRATION
5.1 recommended dose for metastatic CRPC
The recommended dose of ZYTIGA 250 mg is 1,000 mg (four 250mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily.

5.2 recommended dose for metastatic High-risk mHSPC
The recommended dose of Zytiga 250 mg is 1,000 mg (four 250mg tablets) administered orally once daily in combination with prednisone 5mg administered orally once daily...

5.3 important administration instructions
Patients receiving Zytiga 250 mg should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
ZYTIGA 250 MG must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA 250 MG is taken and for at least one hour after the dose of ZYTIGA 250 MG is taken [see Method of administration (5.5)]. The tablets should be swallowed whole with water. Do not crush or chew tablets.
Serum transaminases should be measured prior to starting treatment with Zytiga 250 mg, 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 should be monitored every 2 weeks for the first three months of treatment and monthly thereafter 
In patients with pre-existing hypokalemia or those that develop hypokalemia whilst being treated with ZYTIGA 250 MG, consider maintaining the patient’s potassium level at ≥ 4.0 mM.

For patients who develop Grade ≥ 3 toxicities including hypertension, hypokalemia, oedema and other non-mineralocorticoid toxicities, treatment should be withheld and appropriate medical management should be instituted. Treatment with ZYTIGA 250 MG 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 250 MG or, prednisone, treatment should be resumed the following day with the usual daily dose.

5.4 Dose Modification Guidelines
Hepatic Impairment
In patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of ZYTIGA 250 MG to 250 mg once daily. In patients with moderate hepatic impairment monitor ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. If elevations in ALT and/or AST greater than 5X upper limit of normal (ULN) or total bilirubin greater than 3X ULN occur in patients with baseline moderate hepatic impairment, discontinue ZYTIGA 250 MG and do not re-treat patients with ZYTIGA     250 MG (see sections 5.2 and 6.2).
Do not use ZYTIGA 250 MG in patients with baseline severe hepatic impairment (Child-Pugh Class C).

Hepatotoxicity
For patients who develop hepatotoxicity during treatment with ZYTIGA 250 MG (ALT and/or AST greater than 5X ULN or total bilirubin greater than 3X ULN), interrupt] treatment with ZYTIGA 250 MG (see sections 5.2, 5.7 and 6.2).
Treatment may be restarted at a reduced dose of 750 mg once daily following return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN. For patients who resume treatment, monitor serum transaminases and bilirubin at a minimum of every two weeks for three months and monthly thereafter.
If hepatotoxicity recurs at the dose of 750 mg once daily, re-treatment may be restarted at a reduced dose of 500 mg once daily following return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN.
If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment with ZYTIGA 250 MG.

Permanently discontinue Zytiga 250 mg for patients who develop a concurrent elevation of ALT greater than 3× ULN and total bilirubin greater than 2× ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation [see Warnings and Precautions (5.7)].

Renal impairment
No dosage adjustment is necessary for patients with renal impairment

5.5 Dose Modification Guidelines for strong CYP3A4 inducers
Avoid concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during ZYTIGA 250 MG treatment.
If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA 250 MG dosing frequency to twice a day only during the co- administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day).
Reduce the dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued.
.

Paediatric population
There is no relevant use of ZYTIGA 250mg in the paediatric population.

Method of administration
ZYTIGA 250mg is for oral use.
The tablets must be taken as a single dose once daily on an empty stomach. Zytiga 250mg must be taken at least two hours after aeting and food must not be eaten for at least one hour after taking Zytiga 250mg. Zytiga 250mg tablets must be swallowed whole with water.