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ZYTIGA® 500mg film-coated tablets PRESCRIBING INFORMATION

ACTIVE INGREDIENT(S):

Abiraterone acetate

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

The ZYTIGA® SmPCs are available at: 

Please click the following product name to access the full SmPC
ZYTIGA® 500 mg Tablets

INDICATION(S):

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

DOSAGE & ADMINISTRATION:

Adults: 1000 mg (two 500mg tablets) single daily dose.
Not with food as this increases the systemic exposure (take dose at least two hours after eating; no food for at least one hour post-dose). Swallow whole with water. Take with prednisone or prednisolone: for mHSPC, 5mg daily; for mCRPC, 10 mg daily. Medical castration with LHRH analogue should be continued 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).

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 a 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 and 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 there is a 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 is 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, measure blood sugar frequently in patients with diabetes.
Use with chemotherapy: Safety and efficacy of concomitant use of Zytiga with cytotoxic chemotherapy not established.
Intolerance to excipients: Not to be taken by patients with galactose intolerance, Lapp 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 including those taking Zytiga.
Skeletal muscle effects: Cases of myopathy reported. Some patients had rhabdomyolysis with renal failure. Caution is recommended in patients concomitantly treated with drugs known to be associated with myopathy/rhabdomyolysis.

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 (includes all fractures, with the exception of pathological fracture).
Other side effects: adrenal insufficiency, myocardial infarction, QT prolongation, other arrhythmias, allergic alveolitis, hepatitis fulminant, acute hepatic failure, myopathy, rhabdomyolysis.

Refer to SmPC for other side effects.

FERTILITY/PREGNANCY/LACTATION:

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

INTERACTIONS:

Caution with drugs activated by 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, dose reduction should be considered. 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. 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 is not recommended.

Refer to SmPC for full details of interactions.

LEGAL CATEGORY: POM

PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBERS & BASIC NHS COSTS

PRESENTATIONS PACK SIZES MARKETING AUTHORISATION NUMBER(S) BASIC NHS COSTS
Blister pack 56 tablets EU/1/11/714/002 £2735

MARKETING AUTHORISATION HOLDER: JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.

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

Prescribing information last revised: November 2017

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Janssen-Cilag Limited on 01494 567447 or at dsafety@its.jnj.com.