(a bir A ter one AS e tate)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Zytiga: 250 mg, 500 mg
Brand Names: U.S.
- Antineoplastic Agent, Antiandrogen
Selectively and irreversibly inhibits CYP17 (17 alpha-hydroxylase/C17,20-lyase), an enzyme required for androgen biosynthesis which is expressed in testicular, adrenal, and prostatic tumor tissues. Inhibits the formation of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione.
Vdss: 19,669 ± 13,358 L
Abiraterone acetate is hydrolyzed to the active metabolite abiraterone; further metabolized to inactive metabolites abiraterone sulphate and N-oxide abiraterone sulphate via CYP3A4 and SULT2A1
Feces (~88%); urine (~5%)
Time to Peak
2 hours (Acharya 2012)
14.4 to 16.5 hours (Acharya 2012)
>99%; to albumin and alpha1-acid glycoprotein
Special Populations: Hepatic Function Impairment
Systemic exposure increased approximately 1.1- and 3.6-fold in subjects with mild and moderate hepatic impairment, respectively. Systemic exposure of abiraterone increased by 7- fold and the fraction of free drug increased by 2-fold in subjects with severe baseline hepatic impairment.
Use: Labeled Indications
Prostate cancer: Treatment of metastatic, castration-resistant prostate cancer (in combination with prednisone)
Off Label Uses
Prostate cancer, metastatic or high-risk locally advanced, castration-sensitive
Data from a large, multinational, randomized, controlled phase III study supports the use of abiraterone (in combination with prednisone and androgen-deprivation therapy [ADT]) in patients with newly diagnosed metastatic prostate cancer that is castration-sensitive.[Fizazi 2017] Data from a large, multicenter, randomized multi-stage phase II/III study also supports the use of abiraterone (in combination with prednisolone and long-term ADT) in patients with newly diagnosed metastatic or high-risk locally advanced prostate cancer.[James 2017]
Women who are or may become pregnant
Canadian labeling: Additional contraindication (not in the US labeling): Hypersensitivity to abiraterone acetate or any component of the formulation or container
Prostate cancer, metastatic, castration-resistant: Oral: 1,000 mg once daily (in combination with prednisone 5 mg twice daily)
Prostate cancer, metastatic or high-risk locally advanced, castration-sensitive (off-label use): Oral: 1,000 mg once daily (in combination with prednisone 5 mg once daily and androgen-deprivation therapy; Fizazi 2017) or 1,000 mg once daily (in combination with prednisolone 5 mg once daily and androgen-deprivation therapy; James 2017)
Dosage adjustment for concomitant strong CYP3A4 inducers: Avoid concomitant strong CYP3A4 inducers; if a strong CYP3A4 inducer must be administered concurrently, increase the abiraterone frequency to twice daily (eg, from 1,000 mg once daily to 1,000 mg twice daily). Upon discontinuation of the strong CYP3A4 inducer, reduce abiraterone back to the prior dose and frequency.
Refer to adult dosing.
Dosing: Renal Impairment
No dosage adjustment necessary.
Dosing: Hepatic Impairment
Hepatic impairment prior to treatment initiation:
Mild (Child-Pugh class A): No dosage adjustment necessary.
Moderate (Child-Pugh class B): 250 mg once daily. Permanently discontinue if ALT and/or AST >5 times the upper limit of normal (ULN) or total bilirubin >3 times ULN occur during treatment in patients with baseline moderate hepatic impairment.
Severe (Child-Pugh class C): Do not use.
Hepatotoxicity during treatment:
ALT and/or AST >5 times ULN or total bilirubin >3 times ULN: Withhold treatment until liver function tests return to baseline or ALT and AST ≤2.5 times ULN and total bilirubin ≤1.5 times ULN, then reinitiate at 750 mg once daily.
Recurrent hepatotoxicity on 750 mg/day: Withhold treatment until liver function tests return to baseline or ALT and AST ≤2.5 times ULN and total bilirubin ≤1.5 times ULN, then reinitiate at 500 mg once daily.
Recurrent hepatotoxicity on 500 mg once daily: Discontinue treatment
ALT >3 times ULN and total bilirubin >2 times ULN (in the absence of biliary obstruction or other contributing cause responsible for concurrent elevation): Permanently discontinue treatment
Dosing: Adjustment for Toxicity
Hepatotoxicity: Refer to Dosing: Hepatic Impairment.
Administer abiraterone orally on an empty stomach, at least 1 hour before and 2 hours after food. Note: The prescribing information describes when to give food with respect to abiraterone; no food should be consumed for at least 2 hours before or for at least 1 hour after the abiraterone dose. Swallow tablets whole with water. Do not crush or chew.
Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy
Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy
Choline C 11: Antiandrogens may diminish the therapeutic effect of Choline C 11. Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy
CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Monitor therapy
CYP1A2 Substrates: Abiraterone Acetate may increase the serum concentration of CYP1A2 Substrates. Monitor therapy
CYP2C8 Substrates: Abiraterone Acetate may increase the serum concentration of CYP2C8 Substrates. Monitor therapy
CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy
CYP2D6 Substrates: Abiraterone Acetate may increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Abiraterone Acetate. Management: Avoid whenever possible. If such a combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during concomitant use. Avoid combination
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy
Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy
Indium 111 Capromab Pendetide: Antiandrogens may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination
Metoprolol: CYP2D6 Inhibitors may increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Consider therapy modification
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Monitor therapy
Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Spironolactone: May diminish the therapeutic effect of Abiraterone Acetate. Monitor therapy
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Consider therapy modification
Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Thioridazine: CYP2D6 Inhibitors may increase the serum concentration of Thioridazine. Avoid combination
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Monitor therapy
Adverse reactions reported for use in combination with prednisone.
Cardiovascular: Edema (25% to 27%; includes anasarca, peripheral edema, pitting edema), hypertension (9% to 22%)
Central nervous system: Fatigue (39%), insomnia (14%)
Dermatologic: Bruise (13%)
Endocrine & metabolic: Hypertriglyceridemia (63%), hyperglycemia (57%), hypernatremia (33%), hypokalemia (17% to 28%), hypophosphatemia (24%; grades 3/4: 7%), hot flash (19% to 22%)
Gastrointestinal: Constipation (23%), diarrhea (18% to 22%), dyspepsia (6% to 11%)
Genitourinary: Urinary tract infection (12%)
Hematologic & oncologic: Lymphocytopenia (38%; grades 3/4: 9%)
Hepatic: Increased serum ALT (11% to 42%; grades 3/4: 1% to 6%), increased serum AST (37%; grades 3/4: 3%)
Neuromuscular & skeletal: Joint swelling (30%, includes arthralgia, arthritis, joint discomfort, joint stiffness), myalgia (26%; includes muscle rigidity, muscle spasm, musculoskeletal discomfort, musculoskeletal pain)
Respiratory: Cough (11% to 17%), upper respiratory infection (5% to 13%), dyspnea (12%), nasopharyngitis (11%)
1% to 10%:
Cardiovascular: Cardiac arrhythmia (7%; includes atrial fibrillation, atrial tachycardia, bradycardia, cardiac conduction disturbance, complete atrioventricular block, supraventricular tachycardia, tachycardia), chest pain (4%, includes angina pectoris, chest discomfort, unstable angina pectoris), cardiac failure (2%; includes cardiogenic shock, cardiomegaly, cardiomyopathy, congestive heart failure, left ventricular dysfunction, reduced ejection fraction)
Central nervous system: Falling (6%)
Dermatologic: Skin rash (8%)
Genitourinary: Hematuria (10%), groin pain (7%), urinary frequency (7%), nocturia (6%)
Hepatic: Increased serum bilirubin (7%; grades 3/4: <1%)
Neuromuscular & skeletal: Bone fracture (6%)
Miscellaneous: Fever (9%)
<1% (Limited to important or life-threatening): Acute hepatic failure, adrenocortical insufficiency, fulminant hepatitis, myopathy (includes rhabdomyolysis), pneumonia
Concerns related to adverse effects:
• Adrenocortical insufficiency: Concurrent infection, stress, or interruption of daily corticosteroids is associated with reports of adrenocortical insufficiency. Monitor closely for signs and symptoms of adrenocorticoid insufficiency, which could be masked by adverse events associated with mineralocorticoid excess. Diagnostic testing for adrenal insufficiency may be clinically indicated. Increased corticosteroid doses may be required before, during, and after stress.
• Hepatotoxicity: Severe hepatotoxicity (eg, fulminant hepatitis, acute liver failure, and death) has been reported. Significant increases in liver enzymes have also been observed (higher likelihood in patients with baseline elevations), generally occurring in the first 3 months of treatment. May require dosage reduction, treatment interruption, and/or discontinuation. ALT, AST, and bilirubin should be monitored prior to treatment, every 2 weeks for 3 months and monthly thereafter; patients with hepatic impairment, elevations in liver function tests, or experiencing hepatotoxicity require more frequent monitoring (see dosage adjustment for hepatic impairment and monitoring parameters). Evaluate liver function promptly with signs or symptoms of hepatotoxicity. The safety of retreatment after significant elevations (ALT or AST ≥20 times the upper limit of normal [ULN] and/or total bilirubin ≥10 times ULN) has not been evaluated.
• Mineralocorticoid excess: Increased mineralocorticoids due to CYP17 inhibition may result in hypertension, hypokalemia, and fluid retention (including grade 3 and 4 events). Monitor at least monthly for hypertension, hypokalemia, and fluid retention. Concomitant administration with corticosteroids reduces the incidence and severity of these adverse events.
• Cardiovascular disease: May cause hypertension, hypokalemia, and fluid retention. Control hypertension and correct hypokalemia prior to and during treatment. Use with caution in patients with cardiovascular disease, particularly with heart failure, recent MI, or ventricular arrhythmia. Patients with left ventricular ejection fraction (LVEF) <50% or NYHA class II, III, or IV heart failure were excluded from clinical trials. Monitor at least monthly for hypertension, hypokalemia, and fluid retention.
• Hepatic impairment: Do not use in patients with preexisting severe hepatic impairment (Child-Pugh class C); dosage reduction is recommended in patients with baseline moderate impairment.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Food: Abiraterone must be administered on an empty stomach (administer at least 1 hour before and 2 hours after any food); abiraterone AUC (exposure) may be increased up to 10-fold if administered with a meal.
ALT, AST, and bilirubin prior to treatment, every 2 weeks for 3 months and monthly thereafter; if baseline moderate hepatic impairment (Child-Pugh class B), monitor ALT, AST, and bilirubin prior to treatment, weekly for the first month, every 2 weeks for 2 months then monthly thereafter. If hepatotoxicity develops during treatment (and only after therapy is interrupted and liver function tests have returned to safe levels), monitor ALT, AST, and bilirubin every 2 weeks for 3 months and monthly thereafter. Monitoring of testosterone levels is not necessary. Serum potassium (prior to treatment and at least monthly).
Monitor for signs and symptoms of adrenocorticoid insufficiency; if clinically indicated, consider appropriate diagnostics to confirm adrenal insufficiency. Monitor blood pressure and for fluid retention (prior to treatment and at least monthly). Monitor adherence.
Pregnancy Risk Factor
Adverse effects were observed in animal reproduction studies at doses resulting in less systemic exposure than in humans. Adverse effects were also observed in the reproductive system of animals during toxicology and pharmacology studies. Based on the mechanism of action, abiraterone may cause fetal harm or fetal loss if administered during pregnancy. Abiraterone is not indicated for use in women and is specifically contraindicated in women who are or may become pregnant. It is not known if abiraterone is excreted in semen, therefore, men should use a condom and another method of birth control during treatment and for 1 week following therapy if having intercourse with a woman of reproductive age. Women who are or may become pregnant should wear gloves if contact with tablets may occur.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience flushing, muscle pain, joint pain, joint edema, heartburn, cough, diarrhea, common cold symptoms, rhinitis, pharyngitis, or vomiting. Have patient report immediately to prescriber signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), severe headache, severe dizziness, passing out, vision changes, angina, tachycardia, bradycardia, shortness of breath, excessive weight gain, swelling of arms or legs, severe loss of strength and energy, bruising, bleeding, hematuria, or bone pain (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: miscellaneous antineoplastics
Other brands: Zytiga