Abiraterone Acetate
Abiraterone Acetate Prescribing Information
Dosage and Administration, Important Administration Instructions (Patients receiving abiraterone acetate should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. Abiraterone acetate tablets must be taken as a single dose once daily on an empty stomach. Do not eat food 2 hours before and 1 hour after taking abiraterone acetate. The tablets must be swallowed whole with water. Do not crush or chew tablets. | 8/2021 |
Warnings and Precautions, Hypoglycemia (Severe hypoglycemia has been reported when abiraterone acetate was administered to patients with pre-existing diabetes receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide [see Drug Interactions (7.2)] . Monitor blood glucose in patients with diabetes during and after discontinuation of treatment with abiraterone acetate. Assess if antidiabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia. | 10/2020 |
Abiraterone acetate is indicated in combination with prednisone for the treatment of patients with
- Metastatic castration-resistant prostate cancer (CRPC)
- Metastatic high-risk castration-sensitive prostate cancer (CSPC)
Metastatic castration-resistant prostate cancer:
- Abiraterone acetate 1,000 mg orally once daily with prednisone 5 mg orally twicedaily. ()
2.1 Recommended Dose for Metastatic CRPCThe recommended dose of abiraterone acetate is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with prednisone 5 mg orally
twicedaily.
Metastatic castration-sensitive prostate cancer:
- Abiraterone acetate 1,000 mg orally once daily with prednisone 5 mg orally oncedaily. ()
2.2 Recommended Dose for Metastatic High-risk CSPCThe recommended dose of abiraterone acetate is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with prednisone 5 mg administered orally
oncedaily.
Patients receiving abiraterone acetate should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. Abiraterone acetate tablets must be taken as a single dose once daily on an empty stomach. Do not eat food 2 hours before and 1 hour after taking abiraterone acetate. The tablets must be swallowed whole with water. Do not crush or chew tablets. (
Patients receiving abiraterone acetate should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
Dose Modification:
- For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the abiraterone acetate starting dose to 250 mg once daily. ()
2.4 Dose Modification Guidelines in Hepatic Impairment and HepatotoxicityHepatic ImpairmentIn patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of abiraterone acetate 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 5 × upper limit of normal (ULN) or total bilirubin greater than 3 × ULN occur in patients with baseline moderate hepatic impairment, discontinue abiraterone acetate and do not re-treat patients with abiraterone acetate
[see Use in Specific Populations (8.6)andClinical Pharmacology (12.3)].Do not use abiraterone acetate in patients with baseline severe hepatic impairment (Child-Pugh Class C).
HepatotoxicityFor patients who develop hepatotoxicity during treatment with abiraterone acetate (ALT and/or AST greater than 5 × ULN or total bilirubin greater than 3 × ULN), interrupt treatment with abiraterone acetate
[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 2.5 × ULN and total bilirubin less than or equal to 1.5 × 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 2.5 × ULN and total bilirubin less than or equal to 1.5 × ULN
.If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment with abiraterone acetate.
Permanently discontinue abiraterone acetate for patients who develop a concurrent elevation of ALT greater than 3 × ULN and total bilirubin greater than 2 × ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation
[see Warnings and Precautions (5.3)]. - For patients who develop hepatotoxicity during treatment, hold abiraterone acetate until recovery. Retreatment may be initiated at a reduced dose. Abiraterone acetate should be discontinued if patients develop severe hepatotoxicity. ()
2.4 Dose Modification Guidelines in Hepatic Impairment and HepatotoxicityHepatic ImpairmentIn patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of abiraterone acetate 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 5 × upper limit of normal (ULN) or total bilirubin greater than 3 × ULN occur in patients with baseline moderate hepatic impairment, discontinue abiraterone acetate and do not re-treat patients with abiraterone acetate
[see Use in Specific Populations (8.6)andClinical Pharmacology (12.3)].Do not use abiraterone acetate in patients with baseline severe hepatic impairment (Child-Pugh Class C).
HepatotoxicityFor patients who develop hepatotoxicity during treatment with abiraterone acetate (ALT and/or AST greater than 5 × ULN or total bilirubin greater than 3 × ULN), interrupt treatment with abiraterone acetate
[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 2.5 × ULN and total bilirubin less than or equal to 1.5 × 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 2.5 × ULN and total bilirubin less than or equal to 1.5 × ULN
.If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment with abiraterone acetate.
Permanently discontinue abiraterone acetate for patients who develop a concurrent elevation of ALT greater than 3 × ULN and total bilirubin greater than 2 × ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation
[see Warnings and Precautions (5.3)].
Tablets (500 mg): light purple, oval-shaped, film-coated tablets debossed with "125" on one side.
- Do not use abiraterone acetate in patients with baseline severe hepatic impairment (Child-Pugh Class C). ()
8.6 Patients with Hepatic ImpairmentThe pharmacokinetics of abiraterone were examined in subjects with baseline mild (N=8) or moderate (N=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone after a single oral 1,000 mg dose of abiraterone acetate increased by approximately 1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment, respectively compared to subjects with normal hepatic function.
In another trial, the pharmacokinetics of abiraterone were examined in subjects with baseline severe (N=8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone increased by approximately 7-fold and the fraction of free drug increased 2-fold in subjects with severe baseline hepatic impairment compared to subjects with normal hepatic function.
No dosage adjustment is necessary for patients with baseline mild hepatic impairment. In patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of abiraterone acetate to 250 mg once daily. Do not use abiraterone acetate in patients with baseline severe hepatic impairment (Child-Pugh Class C). If elevations in ALT or AST >5 × ULN or total bilirubin >3 × ULN occur in patients with baseline moderate hepatic impairment, discontinue abiraterone acetate treatment
[see Dosage and Administration (2.4)andClinical Pharmacology (12.3)].For patients who develop hepatotoxicity during treatment, interruption of treatment and dosage adjustment may be required
[see Dosage and Administration (2.4), Warnings and Precautions (5.3),andClinical Pharmacology (12.3)].
None.