Abiratred Special Precautions

Hypertension, hypokalaemia, fluid retention and cardiac failure due to mineralocorticoid excess: Abiraterone may cause hypertension, hypokalaemia and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in 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 (e.g., those on cardiac glycosides), or fluid retention (e.g., those with heart failure), severe or unstable angina pectoris, 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 abiraterone.
Abiraterone should be used with caution in patients with a history of cardiovascular disease. The safety of abiraterone 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 was not established. Before treatment with abiraterone, 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. Serum transaminase levels should be measured prior to starting treatment, 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 or AST 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.
If patients develop severe hepatotoxicity (ALT or AST 20 times the upper limit of normal) anytime while on therapy, treatment should be discontinued and patients should not be re-treated with abiraterone.
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. Abiraterone should be used with caution in patients with moderate hepatic impairment only if the benefit clearly outweighs the possible risk. Abiraterone should not be used in patients with severe hepatic impairment.
There have been rare post-marketing reports of acute liver failure and hepatitis fulminant, some with fatal outcome.
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 abiraterone is continued after corticosteroids are withdrawn, patients should be monitored for symptoms of mineralocorticoid excess.
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.
Hypoglycemia: Cases of hypoglycemia have been reported when abiraterone 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 abiraterone with cytotoxic chemotherapy has not been established.
Combination of abiraterone and prednisone/prednisolone with Ra-223: Treatment with abiraterone and prednisone/prednisolone in combination with Ra-223 is contraindicated 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 abiraterone 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 abiraterone 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: Abiraterone has no or negligible influence on the ability to drive or use machines.