Tablets shown are not actual size.
Drugs That Inhibit or Induce CYP3A4 Enzymes - Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA® treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA® dosing frequency only during the co-administration period [see Dosage and Administration (2.5)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Clinical Pharmacology (12.3)].
Effects of Abiraterone on Drug-Metabolizing Enzymes - ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, consider a dose reduction of the CYP2D6 substrate drug. In a CYP2C8 drug interaction trial in healthy subjects, the AUC of pioglitazone, a CYP2C8 substrate, was increased by 46% when administered with a single dose of ZYTIGA®.
Patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA® [see Clinical Pharmacology (12.3) and Warnings and Precautions (5.6)].
For more information on Dose Modification Guidelines in Hepatic Impairment and Hepatotoxicity and information on Dose Modification Guidelines, see When To Modify Dose.
Co-administration of Prednisone Supresses Adrenocorticotropic Hormone (ACTH) Drive, Reducing the Incidence and Severity of Mineralocorticoid-Related Adverse Reactions1
Adrenocortical Insufficiency - Adrenocortical insufficiency was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of adrenocortical insufficiency if prednisone is stopped or withdrawn, if the prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if clinically indicated, to confirm adrenocortical insufficiency. Increased dosages of corticosteroids may be used before, during, and after stressful situations [see Warnings and Precautions (5.1)].
Schedule for Required Monitoring of Patients Receiving ZYTIGA® Plus Prednisone
|Hypertension, hypokalemia, and fluid retention
|Baseline and at least once a month
|Liver function tests (ALT, AST, bilirubin)
|Baseline and every 2 weeks for the first 3 months of treatment and monthly thereafter†
* Assess more frequently as required.
† Suggested schedule for patients with no or mild baseline hepatic impairment. For patients with baseline hepatic impairment or who develop hepatotoxicity during treatment, see When to Modify Dose. Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C). Please see additional safety information below and full Prescribing Information for complete Dosage and Administration and Warnings and Precautions.
|No/Mild Hepatic Impairment
Impairment (Child-Pugh Class
B) Prior to treatment
Impairment (Child Pugh
Class C) Prior to treatment
|No dosage adjustment is
|Reduce ZYTIGA® dose to
250mg orally QD
|Do not use ZYTIGA® in patients with severe hepatic impairment (Child-Pugh Class C)
OD = once daily; BID= twice daily.
For patients with moderate hepatic impairment (Child-Pugh Class B) monitor serum transaminases (ALT [alanine aminotransferase] and AST [aspartate aminotransferase]) and bilirubin levels
If elevations in ALT and/or AST >5 x ULN (upper limit of normal) or total bilirubin >3 x ULN occur, discontinue ZYTIGA® and do not re-treat patients with ZYTIGA®.
Permanently discontinue ZYTIGA® (abiraterone acetate) for patients who develop a concurrent elevation of ALT greater than3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.
First occurrence of hepatotoxicity
Recurrence of hepatotoxicity (at 750 mg dose)
*LFT: Liver Function Test.
Recurrence of hepatotoxicity (at 500 mg dose)
The safety of ZYTIGA® re-treatment of patients who develop AST or ALT ≥20 x ULN and/or bilirubin ≥10 x ULN is unknown.
For patients taking strong CYP3A4 inducers
For patients taking CYP2D6 and CYP2C8 substrates
References:1. Attard G, Reid AHM, A’HernR, et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2009;27(23):3742-3748. 2. Attard G, Reid AHM, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 2008;26(28):4563-4571. 3. Krasner AS. Glucocorticoid-induced adrenal insufficiency. JAMA. 1999;282(7):671-676.