ZYTIGA

What it is

ZYTIGA contains 250 mg of the active ingredient abiraterone acetate. The 250 mg tablets are white to off-white, oval-shaped film coated tablets, debossed with Teva on one side and "1125" on the other side. Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor that selectively inhibits the enzyme 17α hydroxylase/C17,20-lyase (CYP17).

Approved indications

ZYTIGA is indicated in combination with prednisolone for the treatment of: — newly diagnosed high-risk metastatic hormone sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) — patients with metastatic advanced prostate cancer (castration resistant prostate cancer, mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy (ADT) — patients with mCRPC who have received prior chemotherapy containing a taxane

Dosing overview

The recommended dosage of ZYTIGA is 1 g (four 250 mg tablets) as a single daily dose that must not be taken with food. ZYTIGA tablets must be taken as a single dose once daily on an empty stomach, at least two hours after eating and food must not be eaten for at least one hour after taking ZYTIGA. Serum transaminases and bilirubin 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.

Key safety warnings

Abiraterone should be used with caution in patients with a history of cardiovascular disease. Before treatment, hypertension must be controlled and hypokalaemia must be corrected. Abiraterone may cause hypertension, hypokalaemia and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. In postmarketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalaemia or have underlying cardiovascular conditions while taking abiraterone. Marked increases in liver enzymes leading to drug discontinuation or dosage modification occurred in controlled clinical studies. Very rarely hepatitis fulminant and hepatic failure has been seen. Serum transaminase and bilirubin levels should be measured prior to starting treatment, every two weeks for the first three months of treatment, and monthly thereafter. For patients who develop hepatotoxicity during treatment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) increases above 5 times the upper limit of normal or bilirubin increases above 3 times the upper limit of normal) treatment should be withheld immediately until liver function tests normalise. The use of glucocorticoids could increase hyperglycaemia, therefore blood sugar should be measured frequently in patients with diabetes. Blood glucose should be monitored in patients with diabetes. Isolated cases of hypoglycaemia have been reported when abiraterone acetate plus prednisolone was administered to patients with pre-existing diabetes receiving pioglitazone or repaglinide.

Contraindications

ZYTIGA is contraindicated in women who are or may potentially be pregnant. ZYTIGA is contraindicated in patients with severe hepatic impairment [Child Pugh Class C]. ZYTIGA plus prednisolone is contraindicated in combination with XOFIGO (radium 223 dichloride).

PBS listing

Tablets containing abiraterone acetate 250 mg and 500 mg are each listed on the PBS with authority required restriction, with an ex-manufacturer price of A$775.46.

Regulatory history

ZYTIGA abiraterone acetate 250 mg tablets were first listed on the ARTG on 2012-03-01, and the 500 mg film-coated tablets were first listed on 2017-02-17. In November 2014, the PBAC recommended extending the listing of abiraterone acetate for metastatic castration-resistant prostate cancer to include use prior to chemotherapy. In March 2017, the PBAC recommended a change to allow use with a corticosteroid rather than just prednisone or prednisolone, and in July 2017 recommended a new listing for castration resistant metastatic carcinoma of the prostate for use in combination with a corticosteroid.