Abiraterone Acetate

ABIRATERONE ACETATE- abiraterone acetate tablet
Mylan Institutional Inc.

1 INDICATIONS AND USAGE

Abiraterone acetate tablets are indicated in combination with prednisone for the treatment of patients with

  • Metastatic castration-resistant prostate cancer (CRPC)

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose for Metastatic CRPC

The recommended dose of abiraterone acetate tablets is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with prednisone 5 mg orally twice daily.

2.3 Important Administration Instructions

Patients receiving abiraterone acetate tablets should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. Abiraterone acetate tablets must be taken on an empty stomach, at least one hour before or at least two hours after a meal [see Clinical Pharmacology (12.3)] . The tablets should be swallowed whole with water. Do not crush or chew tablets.

2.4 Dose Modification Guidelines in Hepatic Impairment and Hepatotoxicity

Hepatic Impairment

In patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of abiraterone acetate tablets to 250 mg once daily. 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 abiraterone acetate tablets and do not re-treat patients with abiraterone acetate tablets [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)] .

Do not use abiraterone acetate tablets in patients with baseline severe hepatic impairment (Child-Pugh Class C).

Hepatotoxicity

For patients who develop hepatotoxicity during treatment with abiraterone acetate tablets (ALT and/or AST greater than 5X ULN or total bilirubin greater than 3X ULN), interrupt treatment with abiraterone acetate tablets [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 abiraterone acetate tablets.

Permanently discontinue abiraterone acetate tablets for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation [see Warnings and Precautions (5.3)] .

2.5 Dose Modification Guidelines for Strong CYP3A4 Inducers

Avoid concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during abiraterone acetate tablets treatment.

If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate tablets dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day). Reduce the dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)] .

3 DOSAGE FORMS AND STRENGTHS

Abiraterone Acetate Tablets, USP are available containing 250 mg of abiraterone acetate, USP.

250 mg film-coated tablets: The 250 mg tablets are white, film-coated, oval, unscored tablets debossed with M on one side of the tablet and AB250 on the other side.

250 mg uncoated tablets: The 250 mg tablets are white to off-white, oval, unscored tablets debossed with M on one side of the tablet and AB250 on the other side.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions Due to Mineralocorticoid Excess

Abiraterone acetate tablets may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition . Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with abiraterone acetate tablets. Abiraterone acetate tablets may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1)] . Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with abiraterone acetate tablets.

In the combined data from 4 placebo-controlled trials using prednisone 5 mg twice daily in combination with 1000 mg abiraterone acetate daily, grades 3-4 hypokalemia were detected in 4% of patients on the abiraterone acetate tablets arm and 2% of patients on the placebo arm. Grades 3-4 hypertension were observed in 2% of patients each arm and grades 3-4 fluid retention in 1% of patients each arm. In the combined data from 4 placebo-controlled trials using prednisone 5 mg twice daily in combination with 1000 mg abiraterone acetate daily, grades 3-4 hypokalemia were detected in 4% of patients on the abiraterone acetate tablets arm and 2% of patients on the placebo arm. Grades 3-4 hypertension were observed in 2% of patients each arm and grades 3-4 fluid retention in 1% of patients each arm.

Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. In postmarketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking abiraterone acetate tablets.

The safety of abiraterone acetate tablets in patients with left ventricular ejection fraction < 50% or New York Heart Association (NYHA) Class III or IV heart failure (in COU-AA-301) or NYHA Class II to IV heart failure (in COU-AA-302) has not been established because these patients were excluded from these randomized clinical trials . The safety of abiraterone acetate tablets in patients with left ventricular ejection fraction < 50% or New York Heart Association (NYHA) Class III or IV heart failure (in COU-AA-301) or NYHA Class II to IV heart failure (in COU-AA-302) has not been established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14)] .

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