Zytiga

Q: What are the side effects of Zytiga?

The following are discussed in more detail in other sections of the labeling: Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess [see Warnings and Precautions (5.1) ] . Adrenocortical Insufficiency [see Warnings and Precautions (5.2) ] . Hepatotoxicity [see Warnings and Precautions (5.3) ] . Increased Fractures and Mortality in Combination with… See the full label for the complete list.

Abiraterone acetate · Tablet, Film Coated · Oral

Prescription (Rx) Cytochrome P450 17A1 Inhibitor

Uses

1 INDICATIONS AND USAGE ZYTIGA 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) ZYTIGA is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). ( 1 ) metastatic high-risk castration-sensitive prostate cancer (CSPC). ( 1 )

Dosage and administration

Metastatic castration-resistant prostate cancer: ZYTIGA 1,000 mg orally once daily with prednisone 5 mg orally twice daily. ( 2.1 ) Metastatic castration-sensitive prostate cancer: ZYTIGA 1,000 mg orally once daily with prednisone 5 mg orally once daily. ( 2.2 ) Patients receiving ZYTIGA should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. ZYTIGA 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 ZYTIGA. The tablets must be swallowed whole with water. Do not crush or chew tablets. ( 2.3 ) Dose Modification: For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the ZYTIGA starting dose to 250 mg once daily. ( 2.4 ) 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. ( 2.4 ) 2.1 Recommended Dose for Metastatic CRPC The recommended dose of ZYTIGA is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with prednisone 5 mg orally twice daily. 2.2 Recommended Dose for Metastatic High-risk CSPC The recommended dose of ZYTIGA is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with prednisone 5 mg administered orally once daily. 2.3 Important Administration Instructions Patients receiving ZYTIGA should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. ZYTIGA 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 ZYTIGA. The tablets must 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 ZYTIGA 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 ZYTIGA and do not re-treat patients with ZYTIGA [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C). Hepatotoxicity For patients who develop hepatotoxicity during treatment with ZYTIGA (ALT and/or AST greater than 5 × ULN or total bilirubin greater than 3 × 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 2.5 × 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 ZYTIGA. Permanently discontinue ZYTIGA 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) ] . 2.5 Dose Modification Guidelines for Strong CYP3A4 Inducers Avoid concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA 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) ] .

Dosage forms and strengths

Tablets (500 mg): purple, oval-shaped, film-coated tablets debossed with "AA" one side and "500" on the other side. Tablets (250 mg): white to off-white, oval-shaped tablets debossed with "AA250" on one side. Film-Coated Tablet 500 mg ( 3 ) Uncoated Tablet 250 mg ( 3 )

Contraindications

None. None ( 4 )

Warnings and precautions

Mineralocorticoid excess: Closely monitor patients with cardiovascular disease. 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: Can be severe and fatal. Monitor liver function and modify, interrupt, or discontinue ZYTIGA dosing as recommended. ( 5.3 ) Increased fractures and mortality in combination with radium Ra 223 dichloride: Use of ZYTIGA plus prednisone/prednisolone in combination with radium Ra 223 dichloride is not recommended. ( 5.4 ) Embryo-Fetal Toxicity: ZYTIGA can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception. ( 5.5 , 8.1 , 8.3 ) Hypoglycemia: Severe hypoglycemia has been reported in patients with pre-existing diabetes who are taking medications containing thiazolidinediones (including pioglitazone) or repaglinide. Monitor blood glucose in patients with diabetes and assess if antidiabetic agent dose modifications are required. ( 5.6 ) 5.1 Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess ZYTIGA 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 ZYTIGA. In the combined data from 4 placebo-controlled trials using prednisone 5 mg twice daily in combination with 1,000 mg abiraterone acetate daily, grades 3–4 hypokalemia were detected in 4% of patients on the ZYTIGA 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 LATITUDE (a randomized placebo-controlled, multicenter clinical trial), which used prednisone 5 mg daily in combination with 1,000 mg abiraterone acetate daily, grades 3–4 hypokalemia were detected in 10% of patients on the ZYTIGA arm and 1% of patients on the placebo arm, grades 3–4 hypertension were observed in 20% of patients on the ZYTIGA arm and 10% of patients on the placebo arm. Grades 3–4 fluid retention occurred in 1% of patients each arm [see Adverse Reactions (6) ] . 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 ZYTIGA. The safety of ZYTIGA 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 and LATITUDE) has not been established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14) ] . 5.2 Adrenocortical Insufficiency Adrenal insufficiency occurred in 0.3% of 2230 patients taking ZYTIGA and in 0.1% of 1763 patients taking placebo in the combined data of the 5 randomized, placebo-controlled clinical studies. Adrenocortical insufficiency was reported in patients receiving ZYTIGA in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations [see Warnings and Precautions (5.1) ]. 5.3 Hepatotoxicity In postmarketing experience, there have been ZYTIGA-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure and deaths [see Adverse Reactions (6.2) ] . In the combined data of 5 randomized clinical trials, grade 3–4 ALT or AST increases (at least 5 × ULN) were reported in 6% of 2230 patients who received ZYTIGA, typically during the first 3 months after starting treatment. Patients whose baseline ALT or AST were elevated were more likely to experience liver test elevation than those beginning with normal values. Treatment discontinuation due to ALT and AST increases or abnormal hepatic function occurred in 1.1% of 2230 patients taking ZYTIGA. In these clinical trials, no deaths clearly related to ZYTIGA were reported due to hepatotoxicity events. Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure 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. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient's baseline should prompt more frequent monitoring.

Side effects

The following are discussed in more detail in other sections of the labeling: Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess [see Warnings and Precautions (5.1) ] . Adrenocortical Insufficiency [see Warnings and Precautions (5.2) ] . Hepatotoxicity [see Warnings and Precautions (5.3) ] . Increased Fractures and Mortality in Combination with Radium Ra 223 Dichloride [see Warnings and Precautions (5.4) ]. The most common adverse reactions (≥10%) are fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. ( 6.1 ) The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Two randomized placebo-controlled, multicenter clinical trials (COU-AA-301 and COU-AA-302) enrolled patients who had metastatic CRPC in which ZYTIGA was administered orally at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to patients on the control arm. A third randomized placebo-controlled, multicenter clinical trial (LATITUDE) enrolled patients who had metastatic high-risk CSPC in which ZYTIGA was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg once daily. Placebos were administered to patients in the control arm. Additionally, two other randomized, placebo-controlled trials were conducted in patients with metastatic CRPC. The safety data pooled from 2230 patients in the 5 randomized controlled trials constitute the basis for the data presented in the Warnings and Precautions, Grade 1–4 adverse reactions, and Grade 1–4 laboratory abnormalities. In all trials, a gonadotropin-releasing hormone (GnRH) analog or prior orchiectomy was required in both arms. In the pooled data, median treatment duration was 11 months (0.1, 43) for ZYTIGA-treated patients and 7.2 months (0.1, 43) for placebo-treated patients. The most common adverse reactions (≥10%) that occurred more commonly (>2%) in the ZYTIGA arm were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. The most common laboratory abnormalities (>20%) that occurred more commonly (≥2%) in the ZYTIGA arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia. Grades 3–4 adverse events were reported for 53% of patients in the ZYTIGA arm and 46% of patients in the placebo arm. Treatment discontinuation was reported in 14% of patients in the ZYTIGA arm and 13% of patients in the placebo arm. The common adverse events (≥1%) resulting in discontinuation of ZYTIGA and prednisone were hepatotoxicity and cardiac disorders. Deaths associated with treatment-emergent adverse events were reported for 7.5% of patients in the ZYTIGA arm and 6.6% of patients in the placebo arm. Of the patients in the ZYTIGA arm, the most common cause of death was disease progression (3.3%). Other reported causes of death in ≥5 patients included pneumonia, cardio-respiratory arrest, death (no additional information), and general physical health deterioration. COU-AA-301: Metastatic CRPC Following Chemotherapy COU-AA-301 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. Patients were not eligible if AST and/or ALT ≥2.5 × ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5 × ULN. Table 1 shows adverse reactions on the ZYTIGA arm in COU-AA-301 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with ZYTIGA with prednisone was 8 months. Table 1: Adverse Reactions due to ZYTIGA in COU-AA-301 ZYTIGA with Prednisone (N=791) Placebo with Prednisone (N=394) System/Organ Class All Grades Adverse events graded according to CTCAE version 3.0. Grade 3–4 All Grades Grade 3–4 Adverse reaction % % % % Musculoskeletal and connective tissue disorders Joint swelling/discomfort Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. 30 4.2 23 4.1 Muscle discomfort Includes terms Muscle spasms, Musculoskeletal pain, Myalgia, Musculoskeletal discomfort, and Musculoskeletal stiffness. 26 3.0 23 2.3 General disorders Edema Includes terms Edema, Edema peripheral, Pitting edema, and Generalized edema. 27 1.9 18 0.8 Vascular disorders Hot flush 19 0.3 17 0.3 Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disorders Diarrhea 18 0.6 14 1.3 Dyspepsia 6.1 0 3.3 0 Infections and infestations Urinary tract infection 12 2.1 7.1 0.5 Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinal disorders Cough 11 0 7.6 0 Renal and urinary disorders Urinary frequency 7.2 0.3 5.1 0.3 Nocturia 6.2 0 4.1 0 Injury, poisoning and procedural complications Fractures Includes all fractures with the exception of pathological fracture. 5.9 1.4 2.3 0 Cardiac disorders Arrhythmia Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia. 7.2 1.1 4.6 1.0 Chest pain or chest discomfort Includes terms Angina pectoris, Chest pain, and Angina unstable.

Drug interactions

7 DRUG INTERACTIONS CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency. ( 2.5 , 7.1 ) CYP2D6 Substrates: 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. ( 7.2 ) 7.1 Drugs that Inhibit or Induce CYP3A4 Enzymes Based on in vitro data, ZYTIGA is a substrate of CYP3A4. In a dedicated 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 [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . 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 [see Clinical Pharmacology (12.3) ] . 7.2 Effects of Abiraterone on Drug Metabolizing Enzymes ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In a CYP2D6 drug-drug interaction trial, the C max and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3) ] . In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, 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) ] .

Use in specific populations

Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C). ( 8.6 ) 8.1 Pregnancy Risk Summary The safety and efficacy of ZYTIGA have not been established in females. Based on findings from animal studies and the mechanism of action, ZYTIGA can cause fetal harm and potential loss of pregnancy. There are no human data on the use of ZYTIGA in pregnant women. In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥ 0.03 times the human exposure (AUC) at the recommended dose (see Data ). Data Animal Data In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6–17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients. 8.2 Lactation Risk Summary The safety and efficacy of ZYTIGA have not been established in females. There is no information available on the presence of abiraterone in human milk, or on the effects on the breastfed child or milk production. 8.3 Females and Males of Reproductive Potential Contraception Males Based on findings in animal reproduction studies and its mechanism of action, advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks after the final dose of ZYTIGA [see Use in Specific Populations (8.1) ] . Infertility Based on animal studies, ZYTIGA may impair reproductive function and fertility in males of reproductive potential [see Nonclinical Toxicology (13.1) ]. 8.4 Pediatric Use Safety and effectiveness of ZYTIGA in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of patients receiving ZYTIGA in randomized clinical trials, 70% of patients were 65 years and over and 27% were 75 years and over. No overall differences in safety or effectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Patients with Hepatic Impairment The 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 ZYTIGA 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 ZYTIGA to 250 mg once daily. Do not use ZYTIGA 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 ZYTIGA treatment [see Dosage and Administration (2.4) and Clinical 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) , and Clinical Pharmacology (12.3) ]. 8.7 Patients with Renal Impairment No dosage adjustment is necessary for patients with renal impairment [see Clinical Pharmacology (12.3) ] .

Pregnancy

8.1 Pregnancy Risk Summary The safety and efficacy of ZYTIGA have not been established in females. Based on findings from animal studies and the mechanism of action, ZYTIGA can cause fetal harm and potential loss of pregnancy. There are no human data on the use of ZYTIGA in pregnant women. In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥ 0.03 times the human exposure (AUC) at the recommended dose (see Data ). Data Animal Data In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6–17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of ZYTIGA in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Of the total number of patients receiving ZYTIGA in randomized clinical trials, 70% of patients were 65 years and over and 27% were 75 years and over. No overall differences in safety or effectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Overdosage

Human experience of overdose with ZYTIGA is limited. There is no specific antidote. In the event of an overdose, stop ZYTIGA, undertake general supportive measures, including monitoring for arrhythmias and cardiac failure and assess liver function.

Description

Abiraterone acetate, the active ingredient of ZYTIGA ® is the acetyl ester of abiraterone. Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains either 250 mg or 500 mg of abiraterone acetate. Abiraterone acetate is designated chemically as (3β)-17-(3-pyridinyl) androsta-5,16-dien-3-yl acetate and its structure is: Abiraterone acetate is a white to off-white, non-hygroscopic, crystalline powder. Its molecular formula is C 26 H 33 NO 2 and it has a molecular weight of 391.55. Abiraterone acetate is a lipophilic compound with an octanol-water partition coefficient of 5.12 (Log P) and is practically insoluble in water. The pKa of the aromatic nitrogen is 5.19. ZYTIGA tablets are available in 500 mg film-coated tablets and 250 mg uncoated tablets with the following inactive ingredients: 500 mg film-coated tablets: colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, silicified microcrystalline cellulose, and sodium lauryl sulfate. The coating, Opadry ® II Purple, contains iron oxide black, iron oxide red, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. 250 mg uncoated tablets: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium lauryl sulfate. Chemical Structure

Mechanism of action

12.1 Mechanism of Action Abiraterone acetate (ZYTIGA) is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by 17α-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals [see Warnings and Precautions (5.1) ] . Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. ZYTIGA decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of ZYTIGA on serum testosterone levels. Changes in serum prostate specific antigen (PSA) levels may be observed but have not been shown to correlate with clinical benefit in individual patients.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING ZYTIGA ® (abiraterone acetate) Tablets are available in the strengths and packages listed below: ZYTIGA ® 500 mg film-coated Tablets Purple, oval-shaped tablets debossed with "AA" one side and "500" on the other side. NDC 57894-195-06, 60 tablets available in child-resistant high-density polyethylene bottles ZYTIGA ® 250 mg uncoated Tablets White to off-white, oval-shaped tablets debossed with "AA250" on one side. NDC 57894-150-12, 120 tablets available in child-resistant high-density polyethylene bottles Storage and Handling Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted in the range from 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature] . Keep out of reach of children. Based on its mechanism of action, ZYTIGA may harm a developing fetus. Women who are pregnant or women who may be pregnant should not handle ZYTIGA 250 mg uncoated tablets or other ZYTIGA tablets if broken, crushed, or damaged without protection, e.g., gloves [see Use in Specific Populations (8.1) ] .

Storage

Storage and Handling Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted in the range from 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature] . Keep out of reach of children. Based on its mechanism of action, ZYTIGA may harm a developing fetus. Women who are pregnant or women who may be pregnant should not handle ZYTIGA 250 mg uncoated tablets or other ZYTIGA tablets if broken, crushed, or damaged without protection, e.g., gloves [see Use in Specific Populations (8.1) ] .

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information) Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions Inform patients that ZYTIGA is associated with hypertension, hypokalemia, and peripheral edema that may lead to QT prolongation and Torsades de Pointes in patients who develop hypokalemia while taking ZYTIGA. Advise patients that their blood pressure, serum potassium and signs and symptoms of fluid retention will be monitored clinically at least monthly. Advise patients to adhere to corticosteroids and to report symptoms of hypertension, hypokalemia, or edema to their healthcare provider [see Warnings and Precautions (5.1) ] . Adrenocortical Insufficiency Inform patients that ZYTIGA with prednisone is associated with adrenal insufficiency. Advise patients to report symptoms of adrenocortical insufficiency to their healthcare provider [see Warnings and Precautions (5.2) ] . Hepatotoxicity Inform patients that ZYTIGA is associated with severe hepatotoxicity. Inform patients that their liver function will be monitored using blood tests. Advise patients to immediately report symptoms of hepatotoxicity to their healthcare provider [see Warnings and Precautions (5.3) ] . Hypoglycemia Inform patients that severe hypoglycemia has been reported when ZYTIGA was administered to patients with pre-existing diabetes who were receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide, antidiabetic drugs. Advise patients with diabetes to monitor glucose levels during and after treatment with ZYTIGA [see Warnings and Precautions (5.6) and Drug Interactions (7.2) ]. Use in Combination with Radium Ra 223 Dichloride Advise patients that radium Ra 223 dichloride showed an increase in mortality and an increased rate of fracture when used in combination with ZYTIGA plus prednisone/prednisolone. Inform patients to speak with their healthcare provider about any other medications or treatment they are currently taking for prostate cancer [see Warnings and Precautions (5.4) ] . Dosing and Administration Inform patients that ZYTIGA is taken once daily with prednisone (once or twice daily according to their healthcare provider's instructions) and to not interrupt or stop either of these medications without consulting their healthcare provider. Inform patients receiving GnRH therapy that they need to maintain this treatment during the course of treatment with ZYTIGA. Instruct patients to take ZYTIGA tablets as a single dose once daily on an empty stomach . Instruct patients to not eat food 2 hours before and 1 hour after taking ZYTIGA. ZYTIGA taken with food causes increased exposure and may result in adverse reactions. Instruct patients to swallow tablets whole with water and not to crush or chew the tablets [see Dosage and Administration (2.3) ] . Inform patients that if they miss a dose of ZYTIGA or prednisone, they should take their normal dose the following day. If more than one daily dose is skipped, inform patients to contact their healthcare provider [see Dosage and Administration (2.3) ] . Embryo-Fetal Toxicity Inform patients that ZYTIGA may harm a developing fetus and can cause loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks after the final dose of ZYTIGA [see Use in Specific Populations (8.1) ] . Advise females who are pregnant or women who may be pregnant not to handle ZYTIGA 250 mg uncoated tablets or other ZYTIGA tablets if broken, crushed, or damaged without protection, e.g., gloves [see Use in Specific Populations (8.1) and How Supplied/Storage and Handling (16) ] . Infertility Advise male patients that ZYTIGA may impair fertility [see Use in Specific Populations (8.3) ] .

Label text from the FDA structured product label by Janssen Biotech, Inc. (revised Mar 28, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Abiraterone Acetate in 2 products

Zytiga NDC products (2)

NDC	Strength & form	Labeler	Type
57894-150	Abiraterone Acetate 250 mg/1 Tablet	Janssen Biotech, Inc.	NDA
57894-195	Abiraterone Acetate 500 mg/1 Tablet, Film Coated	Janssen Biotech, Inc.	NDA

Frequently asked questions

What is Zytiga used for?

What are the side effects of Zytiga?

Who makes Zytiga?

Zytiga is listed by 1 labeler in the FDA NDC directory, including Janssen Biotech, Inc..