Zytiga Special Precautions

Hypertension, hypokalaemia and fluid retention due to mineralocorticoid excess: ZYTIGA may cause hypertension, hypokalaemia and fluid retention (see Adverse Reactions) as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition (see Pharmacology: Pharmacodynamics: Mechanism of action under Actions). Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in the incidence and severity of these adverse reactions. Caution is required in treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalaemia or fluid retention, e.g., those with heart failure, recent myocardial infarction or ventricular arrhythmia. In postmarketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia or have underlying cardiovascular conditions while taking ZYTIGA.
ZYTIGA should be used with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with left ventricular ejection fraction (LVEF) <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 301) or NYHA Class II to IV heart failure (in Studies 3011 and 302) was not established (see Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions). Before treatment with ZYTIGA, hypertension must be controlled and hypokalemia must be corrected. Blood pressure, serum potassium and fluid retention should be monitored at least monthly.
Hepatotoxicity and hepatic impairment: Marked increases in liver enzymes leading to treatment discontinuation or dose modification occurred in controlled clinical studies (see Adverse Reactions). Serum transaminase and bilirubin levels should be measured prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment, and monthly thereafter. If clinical symptoms or signs suggestive of hepatotoxicity develop, serum transaminases should be measured immediately. If at any time the ALT rises above 5 times the upper limit of normal or the bilirubin rises above 3 times the upper limit of normal, treatment with ZYTIGA should be interrupted immediately and liver function closely monitored.
Re-treatment with ZYTIGA may only take place only after return of liver function tests to the patient's baseline and at a reduced dose level (see Dosage & Adminstration).
If patients develop severe hepatotoxicity (ALT or AST 20 times the upper limit of normal) anytime while on therapy, ZYTIGA should be discontinued and patients should not be re-treated with ZYTIGA.
There are no data on the clinical safety and efficacy of multiple doses of abiraterone acetate when administered to patients with moderate or severe hepatic impairment (Child Pugh Class B or C). No dose adjustment can be predicted. ZYTIGA should be used with caution in patients with moderate hepatic impairment only if the benefit clearly outweighs the possible risk (see Dosage & Administration and Pharmacology: Pharmacokinetics: Special populations under Actions). ZYTIGA should not be used in patients with severe hepatic impairment (see Dosage & Administration and Pharmacology: Pharmacokinetics: Special populations under Actions).
There have been rare post-marketing reports of acute liver failure and hepatitis fulminant, some with fatal outcome (see Adverse Reactions).
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 Hypertension, hypokalemia and fluid retention due to mineralocorticoid excess as previously mentioned).
In patients on prednisone or prednisolone who are subjected to unusual stress, an increased dosage of a corticosteroid may be indicated before, during and after the stressful situation.
Hypoglycemia: Cases of hypoglycemia have been reported when ZYTIGA was administered to patients with pre-existing diabetes receiving pioglitazone or repaglinide; therefore, blood sugar should be measured frequently in patients with diabetes.
Use with chemotherapy: The safety and efficacy of concomitant use of ZYTIGA with cytotoxic chemotherapy has not been established (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Combination of abiraterone and prednisone/prednisolone with Ra-223: Treatment with abiraterone and prednisone/prednisolone in combination with Ra-223 is contraindicated (see Contraindications) due to an increased risk of fractures and a trend for increased mortality among asymptomatic or mildly symptomatic prostate cancer patients as observed in clinical trials.
It is recommended that subsequent treatment with Ra-223 is not initiated for at least 5 days after the last administration of ZYTIGA in combination with prednisone/prednisolone.
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, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicinal product contains 27.2 mg (1.18 mmol) sodium per dose of four tablets, equivalent to 1.36% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Effects on Ability to Drive and Use Machines: No studies on the effects of ZYTIGA on the ability to drive or use machines have been performed. It is not anticipated that ZYTIGA will affect the ability to drive and use machines.