Prescribing information For Healthcare Professionals Only

ACTIVE INGREDIENT(S):

Abiraterone acetate

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

INDICATION(S):

Taken with prednisone or prednisolone for treatment of adult men with:

• newly diagnosed high risk metastatic hormone sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy
• metastatic castration resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated
• mCRPC whose disease has progressed on or after a docetaxel-based chemotherapy regimen.

DOSAGE & ADMINISTRATION:

Adults: 1000 mg (two 500mg tablets) single daily dose on an empty stomach.
Not with food as this increases the systemic exposure (Zytiga must be taken at least two hours after eating and food must not be eaten for at least one hour after taking Zytiga). Swallow whole with water. Take with prednisone or prednisolone: for mHSPC, 5mg daily; for mCRPC, 10 mg daily. Continue medical castration with LHRH analogue during treatment in patients not surgically castrated.
Children: No relevant use.
Hypokalaemia: In patients with pre-existing, or who develop hypokalaemia during treatment with Zytiga®, consider maintaining potassium level at ≥4.0 mM. Patients who develop Grade ≥ 3 toxicities (hypertension, hypokalaemia, oedema and other non-mineralocorticoid toxicities) stop treatment and start appropriate medical management. Do not restart Zytiga® until symptoms of the toxicity have resolved to Grade 1 or baseline.
Renal impairment: No dose adjustment, however no experience in patients with prostate cancer and severe renal impairment; caution advised.
Hepatotoxicity: If hepatotoxicity develops (ALT or AST > 5x upper limit of normal - ULN), stop treatment immediately until liver function returns to baseline; restart Zytiga® at 500 mg (one tablet) once daily and monitor serum transaminases at least every 2 weeks for 3 months and monthly thereafter (see Special Warnings & Precautions). If hepatotoxicity recurs on reduced dose, stop treatment. If severe hepatotoxicity develops (ALT or AST 20xULN), discontinue Zytiga® and do not restart.
Hepatic impairment: Mild (Child-Pugh class A) - no dose adjustment required. Moderate (Child-Pugh class B) - approximately 4x increased systemic exposure after single oral doses of 1,000 mg. Moderate/Severe (Child-Pugh class B or C) – no clinical data for multiple doses. Use with caution in moderate impairment, benefit should clearly outweigh risk.

CONTRAINDICATIONS:

Pregnancy or potential to be pregnant. Hypersensitivity to active substance or any excipients. Severe hepatic impairment (Child-Pugh Class C). Zytiga plus prednisolone/ prednisone, in combination with Ra-223.

SPECIAL WARNINGS & PRECAUTIONS:

Zytiga® may cause hypertension, hypokalaemia and fluid retention due to increased mineralocorticoid levels.
Cardiovascular: Caution in patients with history of cardiovascular disease. In patients with significant risk for congestive heart failure (history of cardiac failure, uncontrolled hypertension, ischaemic heart disease) consider an assessment of cardiac function before treating (echocardiogram). Safety not established in patients with left ventricular ejection fraction < 50% or NYHA Class II to IV (pre-chemotherapy) and III or IV (post-chemotherapy) heart failure. Before treatment cardiac failure should be treated and cardiac function optimised. Correct and control hypertension, hypokalaemia and fluid retention pre-treatment. Caution in patients whose medical conditions might be compromised by hypertension, hypokalaemia or fluid retention e.g. heart failure, severe or unstable angina pectoris, recent myocardial infarction or ventricular arrhythmia, severe renal impairment. Monitor blood pressure, serum potassium and fluid retention and other signs/symptoms of congestive heart failure before treatment, then every two weeks for 3 months, and monthly thereafter. QT prolongation observed in patients experiencing hypokalaemia with Zytiga® treatment. Consider discontinuation if clinically significant decrease in cardiac function.

Hepatotoxicity & hepatic impairment: Measure serum transaminases pre-treatment and every two weeks for first three months, then monthly. If symptoms/signs suggest hepatotoxicity, immediately measure serum transaminases. If ALT or AST > 5x ULN, stop treatment and monitor liver function. Restart treatment after liver function returns to baseline; use reduced dose (see Dosage and Administration). No clinical data in patients with active or symptomatic viral hepatitis. Rare reports of acute liver failure and hepatitis fulminant, some fatal.
Corticosteroid withdrawal: Monitor for adrenocortical insufficiency if prednisone or prednisolone withdrawn. Monitor for mineralocorticoid excess if Zytiga® continued after corticosteroids withdrawn.
Bone density: Decreased bone density may be accentuated by Zytiga® plus glucocorticoid.
Prior use of ketoconazole: Lower response rates may occur in patients previously treated with ketoconazole for prostate cancer.
Hyperglycaemia: Use of glucocorticoids could increase hyperglycaemia. 

Hypoglycaemia: Cases reported in patients with pre-existing diabetes receiving pioglitazone or repaglinide. Monitor blood sugar in patients with diabetes.
Use with chemotherapy: Safety/efficacy of concomitant use of with cytotoxic chemotherapy not established.
Intolerance to excipients: Not to be taken by patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Take sodium content into account for those on controlled sodium diet.
Potential risks: Anaemia and sexual dysfunction may occur in men with metastatic prostate cancer.
Skeletal muscle effects: Cases of myopathy and rhabdomyolysis reported. Caution recommended in patients concomitantly treated with drugs associated with myopathy/rhabdomyolysis. 
Interactions: Combination of Zytiga and prednisone/prednisolone with Radium 223 contraindicated due to increased risk of fractures and trend for increased mortality among asymptomatic/mildly symptomatic prostate cancer patients. Recommended subsequent treatment with Ra-223 not initiated for at least 5 days after the last administration of Zytiga with prednisone/prednisolone.

SIDE EFFECTS:

Very common: urinary tract infection, hypokalaemia, hypertension, diarrhoea, increased alanine aminotransferase, increased aspartate aminotransferase, peripheral oedema.
Common:sepsis, hypertriglyceridaemia, cardiac failure (including congestive heart failure, left ventricular dysfunction and decreased ejection fraction), angina pectoris, atrial fibrillation, tachycardia, dyspepsia, rash, haematuria, fractures (all fractures, except pathological fracture).
Other side effects: adrenal insufficiency, myocardial infarction, QT prolongation, other arrhythmias, allergic alveolitis, hepatitis fulminant, acute hepatic failure, myopathy, rhabdomyolysis, anaphylactic reactions.

Refer to SmPC for other side effects.

FERTILITY/PREGNANCY/LACTATION:

Not for use in women. Not known if abiraterone or its metabolites are present in semen. Condom is required if patient is engaged in sexual activity with a pregnant woman. If the patient is engaged in sexual activity with a woman of childbearing potential, condom is required along with another effective contraceptive method. Studies have shown that abiraterone acetate affected fertility in male and female rats, but these effects were fully reversible.

INTERACTIONS:

Caution with drugs activated or metabolised by CYP2D6 particularly when there is a narrow therapeutic index (e.g. metoprolol, propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecanide, codeine, oxycodone and tramadol); consider dose reduction. Avoid strong inducers of CYP3A4 (e.g. phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, St John’s wort). Zytiga is a CYP2C8 inhibitor. Monitor for signs of toxicity if combined with drugs with a narrow therapeutic index eliminated predominately by CYP2C8, include pioglitazone and repaglinide. May increase concentrations of drugs eliminated by OATP1B1. Food (see Dosage & Administration).
Caution with medicines known to prolong QT interval or induce Torsade de pointes (e.g. quinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, antiarrhythmic medicinal products, methadone, moxifloxacin and antipsychotics). Use of Zytiga with spironolactone not recommended.

Refer to SmPC for full details of interactions.

LEGAL CATEGORY: POM

MARKETING AUTHORISATION HOLDER: 

UK (Northern Ireland): JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.

UK (Great Britain): JANSSEN-CILAG LIMITED, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK

FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK.

Prescribing information last revised: July 2021