No dosage adjustment is necessary for patients with renal impairment.
Human experience of overdose with ZYTIGA® is limited. There is no specific antidote. In the event of an overdose, stop ZYTIGA® and undertake general supportive measures, including monitoring for arrhythmias and cardiac failure, and assess liver function.
Patients receiving GnRH agonists should be informed that they need to maintain this treatment during the course of treatment with ZYTIGA® + prednisone. The two pivotal Phase 3, randomized placebo-controlled, multicenter clinical studies enrolled patients who had mCRPC and who were using a GnRH agonist or were previously treated with orchiectomy.
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 (2.3)]. 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.
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, exercise caution and 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®.
Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C). ZYTIGA® is not indicated for use in women. ZYTIGA® can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant. Safety and efficacy in pediatric patients have not been established.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Based on its mechanism of action, ZYTIGA® may harm a developing fetus. Therefore, women who are pregnant or women who may be pregnant should not handle ZYTIGA® 250 mg uncoated tablets without protection, eg, gloves.