ZYTIGA in combination with prednisone for the treatment of patients with:

• Metastatic castration-resistant prostate cancer (CRPC)
• Metastatic high-risk castration-sensitive prostate cancer (CSPC)

Patients receiving ZYTIGA should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

ZYTIGA must be taken on an empty stomach, at least one hour before or at least two hours after a meal.

ZYTIGA plus prednisone/prednisolone is not recommended for use in combination with radium 223 dichloride outside of clinical trials.

Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with LVEF < 50% or NYHA Class III or IV heart failure in Study 1 or LVEF < 50% or NYHA Class II to IV heart failure in Study 2 was not established.

Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child Pugh Class C).

In patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of ZYTIGA to 250 mg once daily.

In postmarketing experience, there have been ZYTIGA-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure and deaths.

For patients who develop hepatotoxicity during treatment with ZYTIGA (ALT and/or AST greater than 5 x ULN or total bilirubin greater than 3 x ULN), interrupt treatment with ZYTIGA.

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 2.5 x ULN and total bilirubin less than or equal to 1.5 x 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 2.5 x ULN and total bilirubin less than or equal to 1.5 x ULN.

If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment with ZYTIGA.

Permanently discontinue ZYTIGA for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.

ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly.

Severe hypoglycemia has been reported when ZYTIGA was administered to patients with preexisting diabetes receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide.

Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. In postmarketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking ZYTIGA.

Use caution and monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress.

Avoid concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital).

Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine).

Patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA.

ZYTIGA can cause fetal harm and potential loss of pregnancy. ZYTIGA is not indicated for use in women.

GoToSource

• Use in patients under the age of 18. GoToSource 

• Use in female patients. GoToSource 

• Monotherapy. GoToSource 

• Use for earlier-stage prostate cancer. GoToSource

Fluid retention, hypertension (high blood pressure), hypokalemia (low potassium level ) and urinary tract infections. GoToSource 

Rhabdomyolysis (breakdown of muscle tissue). GoToSource

Pneumonia, dyspnea (trouble breathing), lower respiratory tract infection, liver failure, pulmonary hemorrhage, chest infection and myocardial infarction. GoToSource

Anorexia and oral mucositis (inflammation or ulceration of mucous membranes of digestive tract). GoToSource

Withdrawal syndrome. GoToSource

Migraines. GoToSource

Pulmonary edema (excess fluid in the lungs). GoToSource

Decreased cortisol levels. GoToSource

Elevated aspartate aminotransferase, elevated alanine aminotransferase, thrombocytopenia and neutropenia. GoToSource

Anemia. GoToSource 

Tachycardia (rapid heart heart) and atrial fibrillation (irregular heartbeat). GoToSource

No major injury lawsuits reported.