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ZYTIGA(abiraterone acetate) tablet

2014-06-12 14:57:16 来源: 作者: 【大中小】浏览:347次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ZYTIGA safely and effectively. See full prescribing information for ZYTIGA. ZYTIGA™ (abiraterone acetate) Tablets For Oral Administration Initial U.S. Approval – 2011
INDICATIONS AND USAGE
ZYTIGA is a CYP17 inhibitor indicated for use in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel. (1)
DOSAGE AND ADMINISTRATION
Recommended dose: ZYTIGA 1,000 mg administered orally once daily in combination with prednisone 5 mg administered orally twice daily. ZYTIGA must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. (2.1) For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the ZYTIGA starting dose to 250 mg once daily. (2.2) For patients who develop hepatotoxicity during treatment, hold ZYTIGA until recovery. Retreatment may be initiated at a reduced dose. ZYTIGA should be discontinued if patients develop severe hepatotoxicity. (2.2)
DOSAGE FORMS AND STRENGTHS
Tablet 250 mg (3)
CONTRAINDICATIONS
ZYTIGA is contraindicated in women who are or may become pregnant. (4.1)
WARNINGS AND PRECAUTIONS
Mineralocorticoid excess: Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with LVEF < 50% or NYHA Class III or IV heart failure is not established. Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly. (5.1) Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations. (5.2) Hepatotoxicity: Increases in liver enzymes have led to drug interruption, dose modification and/or discontinuation. Monitor liver function and modify, interrupt, or discontinue ZYTIGA dosing as recommended. (5.3) Food Effect: ZYTIGA must be taken on an empty stomach. Exposure (area under the curve) of abiraterone increases up to 10 fold when abiraterone acetate is taken with meals. (5.4)
ADVERSE REACTIONS
The most common adverse reactions (≥ 5%) are joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, and upper respiratory tract infection. (6) To report SUSPECTED ADVERSE REACTIONS, contact Centocor Ortho Biotech Inc. at 800-457-6399 and www.centocororthobiotech.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration of ZYTIGA with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate. (7)
USE IN SPECIFIC POPULATIONS
Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C). (8.6)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling
Revised: 04/2011

Back to Highlights and Tabs

FULL PRESCRIBING INFORMATION: CONTENTS*

*Sections or subsections omitted from the full prescribing information are not listed

1INDICATIONS AND USAGE

2DOSAGE AND ADMINISTRATION

2.1Recommended Dosage

2.2Dose Modification Guidelines

3DOSAGE FORMS AND STRENGTHS

4CONTRAINDICATIONS

4.1Pregnancy

5WARNINGS AND PRECAUTIONS

5.1Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess

5.2Adrenocortical Insufficiency

5.3Hepatotoxicity

5.4Food Effect

6ADVERSE REACTIONS

6.1Clinical Trial Experience

7DRUG INTERACTIONS

7.1Effects of Abiraterone on Drug Metabolizing Enzymes

7.2Drugs that Inhibit or Induce CYP3A4 Enzymes

8USE IN SPECIFIC POPULATIONS

8.1Pregnancy

8.3Nursing Mothers

8.4Pediatric Use

8.5Geriatric Use

8.6Patients with Hepatic Impairment

8.7Patients with Renal Impairment

10OVERDOSAGE

11DESCRIPTION

12CLINICAL PHARMACOLOGY

12.1Mechanism of Action

12.3Pharmacokinetics

12.4QT Prolongation

13NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, and Impairment of Fertility

13.2Animal Toxicology and/or Pharmacology

14CLINICAL STUDIES

16HOW SUPPLIED/STORAGE AND HANDLING

17PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1INDICATIONS AND USAGE

ZYTIGA in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) who have received prior chemotherapy containing docetaxel.

2DOSAGE AND ADMINISTRATION

2.1Recommended Dosage

The recommended dose of ZYTIGA is 1,000 mg administered orally once daily in combination with prednisone 5 mg administered orally twice daily. ZYTIGA must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken [see Clinical Pharmacology (12.3)]. The tablets should be swallowed whole with water.

2.2Dose Modification Guidelines

Hepatic Impairment

In patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of ZYTIGA to 250 mg once daily. A once daily dose of 250 mg in patients with moderate hepatic impairment is predicted to result in an area under the concentration curve (AUC) similar to the AUC seen in patients with normal hepatic function receiving 1,000 mg once daily. However, there are no clinical data at the dose of 250 mg once daily in patients with moderate hepatic impairment and caution is advised. In patients with moderate hepatic impairment monitor ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. If elevations in ALT and/or AST greater than 5X upper limit of normal (ULN) or total bilirubin greater than 3X ULN occur in patients with baseline moderate hepatic impairment, discontinue ZYTIGA and do not re-treat patients with ZYTIGA [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Avoid ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C), as ZYTIGA has not been studied in this population, and no dose adjustment can be predicted.

Hepatotoxicity

For patients who develop hepatotoxicity during treatment with ZYTIGA (ALT and/or AST greater than 5X ULN or total bilirubin greater than 3X ULN), interrupt treatment with ZYTIGA [see Warnings and Precautions (5.3)]. Treatment may be restarted at a reduced dose of 750 mg once daily following return of liver function tests to the patient's baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN. For patients who resume treatment, monitor serum transaminases and bilirubin at a minimum of every two weeks for three months and monthly thereafter.

If hepatotoxicity recurs at the dose of 750 mg once daily, re-treatment may be restarted at a reduced dose of 500 mg once daily following return of liver function tests to the patient's baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN.

If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment with ZYTIGA. The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.