ABIRATERONE FRESENIUS KABI

This medicinal product should be prescribed by an appropriate healthcare professional. Posology The recommended dose is 1,000 mg (two 500 mg tablets) as a single daily dose that must not be taken with food (see “Method of administration” below).

2). Dosage of prednisolone For mHSPC, Abiraterone Fresenius Kabi is used with 5 mg prednisolone daily. For mCRPC, Abiraterone Fresenius Kabi is used with 10 mg prednisolone daily. Medical castration with luteinising hormone releasing hormone (LHRH) analogue should be continued during treatment in patients not surgically castrated.

Recommended monitoring Serum transaminases 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.

4). 0 mM. For patients who develop Grade ≥ 3 toxicities including hypertension, hypokalaemia, oedema and other non-mineralocorticoid toxicities, treatment should be withheld and appropriate medical management should be instituted. Treatment with Abiraterone Fresenius Kabi 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 Abiraterone Fresenius Kabi, prednisolone, treatment should be resumed the following day with the usual daily dose. 4). Re-treatment following return of liver function tests to the patient’s baseline may be given at a reduced dose of 500 mg (one 500 mg tablet) once daily.

For patients being re-treated, serum transaminases should be monitored at a minimum of every two weeks for three months and monthly thereafter. If hepatotoxicity recurs at the reduced dose of 500 mg daily, treatment should be discontinued.

If patients develop severe hepatotoxicity (ALT or AST 20 times the ULN) anytime while on therapy, treatment should be discontinued and patients should not be re-treated. Hepatic impairment No dose adjustment is necessary for patients with pre-existing mild hepatic impairment, Child-Pugh Class A.

2). 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.

Summary of the safety profile In an analysis of adverse reactions of composite Phase 3 studies with abiraterone acetate, adverse reactions that were observed in ≥10% of patients were peripheral oedema, hypokalaemia, hypertension, urinary tract infection, and alanine aminotransferase increased and/or aspartate aminotransferase increased.

Other important adverse reactions include, cardiac disorders, hepatotoxicity, fractures, and allergic alveolitis. Abiraterone Fresenius Kabi may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic consequence of its mechanism of action.

8%, hypertension 22% vs. 16% and fluid retention (peripheral oedema) 23% vs. 17%, respectively. 0) Grades 3 and 4 hypertension were observed in 7% versus 5%, and fluid retention (peripheral oedema) Grades 3 and 4 were observed in 1% versus 1% of patients, respectively.

Mineralocorticoid reactions generally were able to be successfully managed medically. 4). Tabulated list of adverse reactions In studies of patients with metastatic advanced prostate cancer who were using an LHRH analogue, or were previously treated with orchiectomy, abiraterone acetate was administered at a dose of 1,000 mg daily in combination with low dose prednisone or prednisolone (either 5 or 10 mg daily depending on the indication).

Adverse reactions observed during clinical studies and post-marketing experience are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000) and not known (frequency cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 5) Vascular disorders very common: hypertension Respiratory, thoracic and mediastinal disorders rare: allergic alveolitisa Gastrointestinal disorders very common: diarrhoea common: dyspepsia Hepatobiliary disorders very common: alanine aminotransferase increased and/or aspartate aminotransferase increasedb rare: hepatitis fulminant, acute hepatic failure Skin and subcutaneous tissue disorders common: rash Musculoskeletal and connective tissue disorders uncommon: myopathy, rhabdomyolysis Renal and urinary disorders common: haematuria General disorders and administration site conditions very common: oedema peripheral Injury, poisoning and procedural complications common: fractures** * Cardiac failure also includes congestive heart failure, left ventricular dysfunction and ejection fraction decreased ** Fractures includes osteoporosis and all fractures with the exception of pathological fractures a Spontaneous reports from post-marketing experience b Alanine aminotransferase increased and/or aspartate aminotransferase increased includes ALT increased, AST increased, and hepatic function abnormal.

1). Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in incidence and severity of these adverse reactions. , those with heart failure, severe or unstable angina pectoris, recent myocardial infarction or ventricular arrhythmia and those with severe renal impairment).

Abiraterone Fresenius should be used with caution in patients with a history of cardiovascular disease. The Phase 3 studies conducted with Abiraterone Fresenius excluded patients with uncontrolled hypertension, clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class (NYHA) III or IV heart failure (study 301) or Class II to IV heart failure (studies 3011 and 302) or cardiac ejection fraction measurement of < 50%.

In studies 3011 and 302, patients with atrial fibrillation, or other cardiac arrhythmia requiring medical therapy were excluded. 1). g. echocardiogram). Before treatment with Abiraterone Fresenius, cardiac failure should be treated and cardiac function optimised.

Hypertension, hypokalaemia and fluid retention should be corrected and controlled. During treatment, blood pressure, serum potassium, fluid retention (weight gain, peripheral oedema), and other signs and symptoms of congestive heart failure should be monitored every 2 weeks for 3 months, then monthly thereafter and abnormalities corrected.

QT prolongation has been observed in patients experiencing hypokalaemia in association with Abiraterone Fresenius treatment. 2). 8). 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 ULN, treatment should be interrupted immediately and liver function closely monitored.

1. 6). 2)]. - Abiraterone Fresenius with prednisone or prednisolone is contraindicated in combination with Ra-223.